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FDA approves record eight biosimilars in H1 2024; okays first interchangeable biosimilars for Eylea

Biologics, or complex drugs that are derived from living organisms, have revolutionized treatment of various conditions such as cancer, autoimmune diseases, and chronic illnesses. In 2023, eight out of 10 of the world’s top-selling drugs were biologics, including Merck’s Keytruda, AbbVie’s Humira, and Sanofi’s Dupixent.Due to their high costs, accessibility of biologics has been a challenge. That’s why biosimilars, or game-changing copycats of biologics that provide highly similar yet more affordable alternatives to established biologics, are becoming popular.The first biosimilar — Sandoz’ Zarxio — was approved by the US Food and Drug Administration (FDA) in 2015. Its reference biologic was Amgen’s Neupogen (filgrastim). Since then, the global market for biosimilars has been growing at an impressive pace — between 2015 and 2020, it grew at a whopping compounded annual growth rate (CAGR) of 78 percent, touching US$ 17.9 billion in size. It is expected to continue growing at a CAGR of 15 percent and reach a size of about US$ 75 billion by 2030.Major biosimilar players include Amgen, Sandoz, Samsung Bioepis, Pfizer, Biocon Biologics, Celltrion, Stada Arzneimittel, Accord Healthcare, Fresenius Kabi, Coherus Biosciences, Apotex, and Sanofi. The increasing demand for biosimilars has propelled growth in contract manufacturing. Some of the leading contract manufacturing organizations (CMOs) and contract development and manufacturing organizations (CDMOs) that manufacture biosimilars are Polpharma Biologics, Catalent, Pfizer CentreOne, Lonza, Boehringer Ingelheim BioXcellence, Thermo Fisher Scientific, WuXi Biologics, and FUJIFILM Diosynth Biotechnologies.Access the Interactive Dashboard for Biosimilar Developments (Free Excel)Amgen, Sandoz top list of ‘approved biosimilars’; FDA okays 8 copycats in H1 2024Over the recent years, regulatory agencies like the FDA and the European Medicines Agency (EMA) have established rigorous approval pathways for biosimilars.Since 2015, FDA has approved 53 biosimilars, while the EMA has approved 86 biosimilars. Among the US, European and Canadian markets, Amgen and Sandoz are tied in the first place with 13 approved biosimilars each. Samsung Biologics has nine approved biosimilars, followed by Pfizer with eight and Biocon Biologics with seven. In the first half of this year, FDA set a record by approving eight biosimilars — the highest for H1 of any year. EMA has okayed six biosimilars so far in 2024.In 2023, five biosimilars were approved by the FDA with just one being okayed in the first half. The year marked the end of exclusivity for Humira after 20 years, in which it netted a total of US$ 200 billion in sales. AbbVie’s flagship autoimmune drug has a record 10 biosimilars.Johnson & Johnson’s Stelara also lost exclusivity in 2023 and as many as 11 drugmakers hope to bring its biosimilars to the market. Amgen’s Wezlana was the first biosimilar to Stelara, and it was approved as interchangeable by FDA in October last year.Access the Interactive Dashboard for Biosimilar Developments (Free Excel) FDA approves first interchangeable biosimilar for Eylea, cuts regulatory feeDeveloping a biosimilar costs both money and time. According to Pfizer, developing a biosimilar can take five to nine years and cost over US$ 100 million, not including regulatory fees.In October 2023, FDA slashed its fees with the program fee at US$ 177,397, down from US$ 304,162. The application fees for products that require clinical data has been set at US$ 1,018,753, down from US$ 1,746,745. The application fee for products that don’t require clinical data has been set lower — at US$ 509,377 — down from US$ 873,373 set earlier. This reduction in application fee has propelled demand for contract manufacturing of biosimilars.There has also been a rise in approvals of interchangeable biosimilars this year. Interchangeable biosimilars meet additional requirements and may be substituted for its reference product by a pharmacist without consulting the prescriber. This year saw FDA approve the first interchangeable biosimilars for bone cancer drug denosumab (Prolia and Xgeva) in Jubbonti and Wyost as well as for eculizumab (Soliris) in Bkemv.In May, FDA approved the first interchangeable biosimilars for eye drug aflibercept (Eylea) in Opuviz and Yesafili. Other biosimilars approved in 2024 include Simlandi for adalimumab (Humira), Tyenne for tocilizumab (Actemra), Selarsdi for ustekinumab (Stelara), and Hercessi for trastuzumab (Herceptin).Access the Interactive Dashboard for Biosimilar Developments (Free Excel) Merck’s Keytruda, BMS’ Opdivo, Novartis’ Cosentyx brace for biosimilar competitionHealthcare spending in the US is projected to rise from US$ 4.5 trillion in 2022 to US$ 6 trillion by 2027. While biologics involve just two percent of prescriptions, they account for 46 percent of all pharmaceutical spending. In 2022, US$ 252 billion was spent on biologics.Biosimilar-related savings in 2023 were estimated to be US$ 9.4 billion in the US and € 10 billion (US$ 10.68 billion) in Europe. With expensive and widely used drugs like AbbVie’s Humira, J&J’s Stelara, and Regeneron’s Eylea coming under competition, US savings are projected to reach US$ 181 billion through 2027. Between 2026 and 2032, about 39 blockbusters are set to lose exclusivity in the US and Europe. Merck’s Keytruda (pembrolizumab) was the world’s top-selling drug last year, generating US$ 25 billion in sales. Its patent is set to expire in 2028 with sales expected to drop 19 percent to US$ 27.4 billion in 2029 from US$ 33.7 billion the previous year. Samsung Bioepis and Amgen initiated phase 3 trials of pembrolizumab in April and May of this year, respectively.Opdivo (nivolumab), belonging to the same class of drugs, competes with Keytruda and is also set to lose patent protection in 2028. It hauled in US$ 10 billion in total global sales in 2023 for Bristol Myers Squibb. The key patents of Novartis’ Cosentyx (secukinumab) are set to expire between 2025 and 2026. Cosentyx saw sales of US$ 5 billion in 2023. Taizhou Mabtech Pharmaceutical and Bio-Thera Solutions are conducting phase 3 trials of secukinumab.Access the Interactive Dashboard for Biosimilar Developments (Free Excel) Our viewWith over 2 billion people worldwide unable to access life-saving medicines, biosimilars hold the key to healthcare accessibility. In 2023, a record 13 biosimilars were launched in the market — the highest for a single year. And this included nine much-anticipated biosimilars to AbbVie’s Humira. In April this year, FDA announced a Biosimilars Action Plan to streamline the development of biosimilars. With a sharp focus on biosimilars, we expect more records to be broken in the near term. New launches of biosimilars to drugs like J&J’s Stelara, Regeneron’s Eylea and Merck’s Keytruda will surely help in creating new records.

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27 Jun 2024

Top Pharma Companies & Drugs in 2021: Covid vaccines, pills cause churn in list

Every year, the list of top pharmaceutical products and companies by sales sees some churn. But the year 2021 was a lot different — it saw the pharma industry landscape change dramatically. It was a year when the industry was busy developing vaccines and therapies so that the world could recover from the Covid-19 pandemic. And this resulted in many drugmakers raking in billions of dollars in sales. As a result, the top company of 2020 in terms of pharmaceutical sales — Roche — slipped to the number five spot, while Pfizer, which was at number eight in 2020 after spinning off its generic business, moved up to the number one slot. The year proved to be a good one for pharmaceutical companies. Interestingly, last year none of the top 20 pharmaceutical companies saw a decline in their revenue. View Our Interactive Dashboard on Top Drugs by Sales in 2021 (Free Excel Available) Pfizer’s Comirnaty steals the show The company that reaped the maximum gains from its Covid vaccine was Pfizer. Comirnaty (tozinameran) was the top selling pharmaceutical product of 2021, posting global revenues of US$ 36.8 billion. This messenger-RNA Covid-19 vaccine, developed along with its German partner BioNTech, catapulted Pfizer to the slot of the top company by sales in 2021. Pfizer’s global topline grew from US$ 41.7 billion in 2020 to US$ 81.3 billion in 2021. In 2020, Pfizer was at number eight, behind Roche, Novartis, GSK, AbbVie, J&J, Merck and BMS. In 2021, it took a lead of billions of dollars on all these companies. The second largest drug company by sales — AbbVie — was way down at US$ 56.1 billion in global revenues. In fact, Comirnaty has become the fastest-selling drug in the history of the pharmaceutical industry. Back in December 2020, when both Comirnaty and Moderna’s Spikevax had bagged the US Food and Drug Administration’s emergency use authorization (EUA), there was a lot of uncertainty around how the promised doses would be delivered across the world. But both Comirnaty and Spikevax have proven to be a resounding success. Spikevax emerged as the third largest selling pharmaceutical product of 2021, bringing in US$ 17.7 billion for Moderna. Analysts expect both Pfizer-BioNTech and Moderna to sell even more vaccines in 2022. The reasons are manifold. First, SARS-CoV-2 is able to mutate often, and is unlikely to be eradicated in the near future, creating a need for booster shots. Second, the younger age groups are still to get vaccinated. Along with Comirnaty, Pfizer is battling Covid-19 with its antiviral pill, Paxlovid. Though the sales of Paxlovid have nosedived of late, Pfizer expects Comirnaty and Paxlovid to help the New York-headquartered drug behemoth achieve US$ 100 billion in 2022 revenues. View Our Interactive Dashboard on Top Drugs by Sales in 2021 (Free Excel Available) AbbVie moves up, sans Covid product; Roche slips to number five With no Covid-19 related products, AbbVie did fairly well in 2021 — it moved up from the number four spot in 2020 to number two position, thanks to its Allergan acquisition, cash cow Humira (adalimumab), the continued success of its cancer drug Imbruvica (ibrutinib) and an increase in sale of its psoriasis treatment Skyrizi (risankizumab) by a whopping 85 percent in 2021. Humira brought in sales of US$ 21.2 billion for AbbVie in 2021. However, things may change soon, with biosimilars of Humira slated to enter the market in 2023. The years 2022 and 2023 are likely to be transition years for AbbVie, as it works to build the market for its Humira successors — Rinvoq and Skyrizi. Roche emerged as a big loser in 2021, as several copycats of its blockbuster drugs hit the market. Copycats to Roche’s three blockbuster cancer drugs—Avastin, Herceptin and Rituxan—eroded US$ 4.9 billion (CHF 4.73 billion) from the company’s sales in 2021. A large chunk of growth for Roche came from its multiple sclerosis med Ocrevus, hemophilia drug Hemlibra, inflammatory disease therapy Actemra and PD-L1 inhibitor Tecentriq. The pandemic resulted in lower-than-expected sales of Ocrevus (ocrelizumab) due to fears around its immunosuppressive effects. Like Roche, Novartis also slipped last year. It fell from number two in 2020 to the number four slot in 2021. Essentially, Novartis is struggling with a relatively lackluster pipeline. It had sold its 33 percent stake in Roche last year for US$ 20.7 billion. It plans to use that sum for acquisitions in order to beef up its pipeline. The Swiss drugmaker has also drawn up a restructuring plan that includes layoffs of thousands of employees. Before the pandemic, Merck’s Keytruda was touted as the drug that would overtake Humira at the top in 2024. The checkpoint inhibitor has continued to grow impressively, adding new indications and treatment lines. Keytruda is now used in close to 40 indications. With US$ 17.2 billion in sales, Keytruda emerged as the fourth largest selling drug of 2022. Overall though, Merck slipped from number six to the number eight slot. This was due to the fact that Merck had spun out its women’s health, biosimilars and established brands businesses into Organon. However, its Covid-19 antiviral pill — Molnupiravir — was able to compensate for the lost revenue. Though the FDA is yet to grant the drug a full approval (it bagged an EUA in December 2021), advance sales agreements helped it rack up US$ 952 million in sales in the fourth quarter. View Our Interactive Dashboard on Top Drugs by Sales in 2021 (Free Excel Available) BMS moves up with Eliquis, Revlimid; J&J lands at number three Bristol Myers Squibb (BMS) moved up from number seven in 2020 to number six, thanks to two of its drugs that made it to top 10 — anticoagulant Eliquis at number five and oncology drug Revlimid at number six. However, Revlimid will soon face competition — four generic companies now have the approval to sell their versions of Revlimid (lenalidomide) after March 2022. Revlimid sales are expected to drop from US$ 12.9 billion to just US$ 2.06 billion in 2026. BMS posted US$ 46.4 billion in global revenues, a nine percent increase from US$ 42.5 billion reported in 2020. In immuno-oncology, Opdivo brought in US$ 7.52 billion in sales, while Yervoy drew in sales of US$ 2 billion (an increase of 20 percent). J&J’s pharma division brought in US$ 52.1 billion in revenues last year, an increase of 14 percent over its revenues of US$ 45.6 billion posted in 2020. Drugs like Darzalex (for multiple myeloma), Stelara and its Covid-19 vaccine brought in growth during 2021, helping J&J move up from number five to the number three slot. J&J’s Covid-19 vaccine brought in US$ 2.4 billion in sales. View Our Interactive Dashboard on Top Drugs by Sales in 2021 (Free Excel Available) GSK bags approval for shingles vaccine; Takeda suffers setbacks GlaxoSmithKline (GSK) slipped four places — from number three in 2020 to number seven in 2021. Though GSK did not have a drug in the top 10, sales of GSK and Vir Biotechnology’s Covid-19 antibody treatment sotrovimab helped produce a seven percent increase in its 2021 revenue. The British drugmaker also bagged a critical FDA approval — its vaccine to prevent shingles (herpes zoster), Shingrix, bagged the agency’s nod in July. GSK hopes to double the sales of Shingrix by 2026. GSK is also undergoing a major transformation, and plans to demerge its consumer health unit this year. The unit generated revenues of £9.6 billion (US$ 13 billion) last year, and GSK sees the demerger as a necessary step to fuel growth through the development of new vaccines and specialty medicines. Sanofi managed to retain its ninth slot, even as its global turnover increased from US$ 39.3 billion (Euro 36.04 billion) to US$ 41.6 billion (Euro 37.76 billion). It snapped up Kymab, Tidal Therapeutics, Translate Bio, Kadmon Holdings, Origimm Biotechnology and Amunix in deals that bolstered its presence in immunology, immuno-oncology and vaccines. Dealmaking is on the French drugmaker’s menu for 2022 and beyond, Sanofi’s CFO said at this year’s virtual JP Morgan Healthcare Conference. AstraZeneca’s global revenues grew from US$ 26.6 billion in 2020 to US$ 37.4 billion in 2021. However, its rank fell from nine in 2020 to 10 in 2021. AstraZeneca wrapped up the US$ 39 billion acquisition of Alexion in July 2021. Alexion’s rare disease franchise—led by C5 inhibitors Soliris and Ultomiris—added an extra US$ 3.1 billion to Astra’s top line last year. Takeda suffered several clinical and regulatory setbacks in 2021, which it labeled as an “inflection year.” For Gilead, sales of its Covid-19 antiviral Veklury brought in US$ 5.6 billion last year, helping its revenues grow by 11 percent. View Our Interactive Dashboard on Top Drugs by Sales in 2021 (Free Excel Available) Our view If anything, the pandemic has taught us that change is the only constant. It has also taught us that products can become blockbusters in a matter of a few months. The industry landscape continues to change. On the one hand, we are seeing people scrambling to get Covid vaccines and booster shots, on the other hand, the FDA has limited the use of monoclonal antibodies, such as Eli Lilly’s bamlanivimab and etesevimab and Regeneron’s REGEN-COV (casirivimab and imdevimab), in treating Covid caused by the Omicron variant. The FDA has also pulled the authorization granted to GSK and Vir Biotechnology’s antibody therapy this month, citing data that suggested it was unlikely to be effective against the dominant Omicron sub-variant. And last week, there was news that demand for Pfizer’s antiviral pill Paxlovid has remained unexpectedly low. The supply of Paxlovid, which reduced hospitalizations or deaths in high-risk patients by around 90 percent in a clinical trial, has far outstripped demand in many countries like the US, the UK and South Korea. Though Pfizer is hopeful of crossing US$ 100 billion in revenue this year, much depends on how the pandemic pans out and what new research has to say about the novel coronavirus. A lot will change once the pandemic becomes endemic. The first four months of 2022 tell us that vaccines like Comirnaty and Spikevax will continue to perform well. But two years down the line, our charts could look very different.

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28 Apr 2022

Top drugs and pharmaceutical companies of 2019 by revenues

Acquisitions and spin-offs dominated headlines in 2019 and the tone was set very early with Bristol-Myers Squibb acquiring New Jersey-based cancer drug company Celgene in a US$ 74 billion deal announced on January 3, 2019. After factoring in debt, the deal value ballooned to about US$ 95 billion, which according to data compiled by Refinitiv, made it the largest healthcare deal on record. In the summer, AbbVie Inc, which sells the world’s best-selling drug Humira, announced its acquisition of Allergan Plc, known for Botox and other cosmetic treatments, for US$ 63 billion. While the companies are still awaiting regulatory approval for their deal, with US$ 49 billion in combined 2019 revenues, the merged entity would rank amongst the biggest in the industry. View Our Interactive Dashboard on Top drugs by sales in 2019 (Free Excel Available) The big five by pharmaceutical sales — Pfizer, Roche, J&J, Novartis and Merck Pfizer continued to lead companies by pharmaceutical sales by reporting annual 2019 revenues of US$ 51.8 billion, a decrease of US$ 1.9 billion, or 4 percent, compared to 2018. The decline was primarily attributed to the loss of exclusivity of Lyrica in 2019, which witnessed its sales drop from US$ 5 billion in 2018 to US$ 3.3 billion in 2019. In 2018, Pfizer’s then incoming CEO Albert Bourla had mentioned that the company did not see the need for any large-scale M&A activity as Pfizer had “the best pipeline” in its history, which needed the company to focus on deploying its capital to keep its pipeline flowing and execute on its drug launches. Bourla stayed true to his word and barring the acquisition of Array Biopharma for US$ 11.4 billion and a spin-off to merge Upjohn, Pfizer’s off-patent branded and generic established medicines business with Mylan, there weren’t any other big ticket deals which were announced. The Upjohn-Mylan merged entity will be called Viatris and is expected to have 2020 revenues between US$ 19 and US$ 20 billion and could outpace Teva to become the largest generic company in the world, in term of revenues. Novartis, which had followed Pfizer with the second largest revenues in the pharmaceutical industry in 2018, reported its first full year earnings after spinning off its Alcon eye care devices business division that had US$ 7.15 billion in 2018 sales. In 2019, Novartis slipped two spots in the ranking after reporting total sales of US$ 47.4 billion and its CEO Vas Narasimhan continued his deal-making spree by buying New Jersey-headquartered The Medicines Company (MedCo) for US$ 9.7 billion to acquire a late-stage cholesterol-lowering therapy named inclisiran. As Takeda Pharmaceutical Co was busy in 2019 on working to reduce its debt burden incurred due to its US$ 62 billion purchase of Shire Plc, which was announced in 2018, Novartis also purchased the eye-disease medicine, Xiidra, from the Japanese drugmaker for US$ 5.3 billion. Novartis’ management also spent a considerable part of 2019 dealing with data-integrity concerns which emerged from its 2018 buyout of AveXis, the gene-therapy maker Novartis had acquired for US$ 8.7 billion. The deal gave Novartis rights to Zolgensma, a novel treatment intended for children less than two years of age with the most severe form of spinal muscular atrophy (SMA). Priced at US$ 2.1 million, Zolgensma is currently the world’s most expensive drug. However, in a shocking announcement, a month after approving the drug, the US Food and Drug Administration (FDA) issued a press release on data accuracy issues as the agency was informed by AveXis that its personnel had manipulated data which the FDA used to evaluate product comparability and nonclinical (animal) pharmacology as part of the biologics license application (BLA), which was submitted and reviewed by the FDA. With US$ 50.0 billion (CHF 48.5 billion) in annual pharmaceutical sales, Swiss drugmaker Roche came in at number two position in 2019 as its sales grew 11 percent driven by its multiple sclerosis medicine Ocrevus, haemophilia drug Hemlibra and cancer medicines Tecentriq and Perjeta. Roche’s newly introduced medicines generated US$ 5.53 billion (CHF 5.4 billion) in growth, helping offset the impact of the competition from biosimilars for its three best-selling drugs MabThera/Rituxan, Herceptin and Avastin. In late 2019, after months of increased antitrust scrutiny, Roche completed its US$ 5.1 billion acquisition of Spark Therapeutics to strengthen its presence in gene therapy. Last year, J&J reported almost flat worldwide sales of US$ 82.1 billion. J&J’s pharmaceutical division generated US$ 42.20 billion and its medical devices and consumer health divisions brought in US$ 25.96 billion and US$ 13.89 billion respectively. Since J&J’s consumer health division sells analgesics, digestive health along with beauty and oral care products, the US$ 5.43 billion in consumer health sales from over-the-counter drugs and women’s health products was only used in our assessment of J&J’s total pharmaceutical revenues. With combined pharmaceutical sales of US$ 47.63 billion, J&J made it to number three on our list. While the sales of products like Stelara, Darzalex, Imbruvica, Invega Sustenna drove J&J’s pharmaceutical business to grow by 4 percent over 2018, the firm had to contend with generic competition against key revenue contributors Remicade and Zytiga. US-headquartered Merck, which is known as MSD (short for Merck Sharp & Dohme) outside the United States and Canada, is set to significantly move up the rankings next year fueled by its cancer drug Keytruda, which witnessed a 55 percent increase in sales to US$ 11.1 billion. Merck reported total revenues of US$ 41.75 billion and also announced it will spin off its women’s health drugs, biosimilar drugs and older products to create a new pharmaceutical company with US$ 6.5 billion in annual revenues. The firm had anticipated 2020 sales between US$ 48.8 billion and US$ 50.3 billion however this week it announced that the coronavirus pandemic will reduce 2020 sales by more than $2 billion. View Our Interactive Dashboard on Top drugs by sales in 2019 (Free Excel Available) Humira holds on to remain world’s best-selling drug AbbVie’s acquisition of Allergan comes as the firm faces the expiration of patent protection for Humira, which brought in a staggering US$ 19.2 billion in sales last year for the company. AbbVie has failed to successfully acquire or develop a major new product to replace the sales generated by its flagship drug. In 2019, Humira’s US revenues increased 8.6 percent to US$ 14.86 billion while internationally, due to biosimilar competition, the sales dropped 31.1 percent to US$ 4.30 billion. Bristol Myers Squibb’s Eliquis, which is also marketed by Pfizer, maintained its number two position and posted total sales of US$ 12.1 billion, a 23 percent increase over 2018. While Bristol Myers Squibb’s immunotherapy treatment Opdivo, sold in partnership with Ono in Japan, saw sales increase from US$ 7.57 billion to US$ 8.0 billion, the growth paled in comparison to the US$ 3.9 billion revenue increase of Opdivo’s key immunotherapy competitor Merck’s Keytruda. Keytruda took the number three spot in drug sales that previously belonged to Celgene’s Revlimid, which witnessed a sales decline from US$ 9.69 billion to US$ 9.4 billion. Cancer treatment Imbruvica, which is marketed by J&J and AbbVie, witnessed a 30 percent increase in sales. With US$ 8.1 billion in 2019 revenues, it took the number five position. View Our Interactive Dashboard on Top drugs by sales in 2019 (Free Excel Available) Vaccines – Covid-19 turns competitors into partners This year has been dominated by the single biggest health emergency in years — the novel coronavirus (Covid-19) pandemic. As drugs continue to fail to meet expectations, vaccine development has received a lot of attention. GSK reported the highest vaccine sales of all drugmakers with total sales of US$ 8.4 billion (GBP 7.16 billion), a significant portion of its total sales of US$ 41.8 billion (GBP 33.754 billion). US-based Merck’s vaccine division also reported a significant increase in sales to US$ 8.0 billion and in 2019 received FDA and EU approval to market its Ebola vaccine Ervebo. This is the first FDA-authorized vaccine against the deadly virus which causes hemorrhagic fever and spreads from person to person through direct contact with body fluids. Pfizer and Sanofi also reported an increase in their vaccine sales to US$ 6.4 billion and US$ 6.2 billion respectively and the Covid-19 pandemic has recently pushed drugmakers to move faster than ever before and has also converted competitors into partners. In a rare move, drug behemoths — Sanofi and GlaxoSmithKline (GSK) —joined hands to develop a vaccine for the novel coronavirus. The two companies plan to start human trials in the second half of this year, and if things go right, they will file for potential approvals by the second half of 2021. View Our Interactive Dashboard on Top drugs by sales in 2019 (Free Excel Available) Our view Covid-19 has brought the world economy to a grinding halt and shifted the global attention to the pharmaceutical industry’s capability to deliver solutions to address this pandemic. Our compilation shows that vaccines and drugs for infectious diseases currently form a tiny fraction of the total sales of pharmaceutical companies and few drugs against infectious diseases rank high on the sales list. This could well explain the limited range of options currently available to fight Covid-19. With the pandemic currently infecting over 3 million people spread across more than 200 countries, we can safely conclude that the scenario in 2020 will change substantially. And so should our compilation of top drugs for the year. View Our Interactive Dashboard on Top drugs by sales in 2019 (Free Excel Available)

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29 Apr 2020

2017 – Recap of Warning Letters, Import Alerts and Non-Compliances

Data integrity continued to be a hot topic in the pharmaceutical industry through 2017. According to a recent analysis by GMP (good manufacturing practices) intelligence expert, Barbara Unger, approximately 65 percent of all US Food and Drug Administration (USFDA) warning letters issued in FY2017 (October 1, 2016 until September 30, 2017) included a data integrity component. However, in the previous year, this number was even higher — at 79 percent — implying there has been a decline in non-compliance incidents pertaining to data integrity in 2017. Click here for our compilation of all non-compliances in 2017 (Excel version available) for FREE! 2017’s recurring concern – a failure to thoroughly investigate problems In PharmaCompass’ 2016 compilation, serious charges of blatant data manipulation surfaced at organizations around the world. In 2017, we witnessed a reduction in data-integrity violations uncovered at pharmaceutical manufacturers due to the absence of audit trail software in quality control testing equipment. However, the implementation of audit trails has resulted in the emergence of a new failing – the improper handling of out-of-specification (OOS) results. Failure “to thoroughly investigate any unexplained discrepancy or failure of a batch” became a recurring theme in concerns highlighted at major generic players like Mylan, Fresenius, Teva, Dr Reddy’s, Hetero Labs and Lupin. In the case of Fresenius’ oncology API plant in India, USFDA investigators found employees had halted and invalidated HPLC (high-performance liquid chromatography) analyses nearly 250 times when they believed the tests were going to end with OOS results. The USFDA warned Fresenius SE after the company’s Indian plant that makes cancer-drug ingredients for the US market aborted hundreds of drug-quality tests. Click here for our compilation of all non-compliances in 2017 (Excel version available) for FREE! The situation at Lupin wasn’t much better as the warning letter issued to its formulation manufacturing facilities in Goa and Indore (Pithampur Unit II) said the company failed to “thoroughly review any unexplained discrepancy” as Lupin invalidated approximately 96 percent of all OOS results obtained at Pithampur and over 75 percent of them in Goa. Failure to resolve recurring problems also led the USFDA to tell Meridian Medical Technologies, a division of Pfizer that makes the EpiPen injector device (sold by Mylan NV), that serious component and product failures had been associated with patient deaths. In its warning letter, the USFDA said the Pfizer unit failed to adequately investigate problems at its manufacturing facility in Brentwood, Missouri. It also did not take appropriate corrective actions before a USFDA inspection earlier this year. Meridian had received hundreds of complaints that the EpiPen device, which is used to combat serious allergic reactions, failed to operate during life-threatening emergencies. Click here for our compilation of all non-compliances in 2017 (Excel version available) for FREE! Non-compliances at finished drug producers outnumbered those at API facilities During 2017, the number of finished pharmaceutical companies cited for compliance concerns significantly outnumbered the number of active pharmaceutical ingredient (API) producers. While the FDA issued 48 warning letters to drug product manufacturers, API producers received only 18 warning letters. The actions by the European regulators was similar — 15 non-compliance certificates were issued to finished drug producers, as compared to only two API manufactures who were found lagging behind in compliance standards. China, India and the United States continued to lead the countries where regulators found most shortcomings. As compared to the previous year, in 2017 regulators issued fewer non-compliance certifications as the FDA had been hampered by staffing shortages. As a result, the FDA’s inspections in India “dropped 27 percent in fiscal 2017 from a year earlier, to 185 from 252.” Click here for our compilation of all non-compliances in 2017 (Excel version available) for FREE! In 2017, EU and FDA started their mutual recognition program. But will it work? 2017 was also a landmark year for the US and European regulators as the USFDA and the European Medicines Agency (EMA) announced their program for mutual recognition of inspections of drug manufacturers, which became operational on November 1, 2017. The FDA will now recognize eight EU drug regulators – from Austria, Croatia, France, Italy, Malta, Spain, Sweden and the UK – as capable of conducting inspections of manufacturing facilities that meet the USFDA requirements. This is an unprecedented move — prior to this, the USFDA had never recognized another country’s inspectorate. As part of the agreement, the European Commission (EC), the US FDA and the EMA signed a confidentiality commitment that allows the USFDA to share non-public and commercially confidential information, including trade secret information relating to inspections with European regulators. As the mutual recognition of inspections program goes live, there were examples of many companies that were found to be consistently out of compliance by both the FDA and regulators from the EU. Yet, there were cases where the regulators came to different conclusions about the state of a particular facility they had inspected. While European regulators had raised compliance concerns at Biocon, the company went ahead and got an FDA nod for its biosimilar of Roche’s blockbuster cancer drug — Herceptin. Click here for our compilation of all non-compliances in 2017 (Excel version available) for FREE! The case of Qinhuangdao Zizhu — when WHO and FDA differed In another case, an inspection conducted by the USFDA at Qinhuangdao Zizhu Pharmaceutical from November 28 to December 1, 2016 uncovered significant data integrity concerns and failures in the level of adherence to current good manufacturing practices (cGMPs) for APIs. In the warning letter issued to the firm, the laboratory analysts admitted to the FDA inspectors that they had been “setting the clock back and repeating analyses for undocumented reasons.” At Qinhuangdao Zizhu, “initial sample results were overwritten or deleted” and the company “reported only the passing results from repeat analyses”. In addition to not having effective measures to control data within their computerized systems, the FDA investigators found that the firm “relied on incomplete information” to determine whether Qinhuangdao Zizhu’s drugs met established specifications. The investigators found “a recurring practice of re-testing samples until acceptable results were obtained” and that batch production records “contained blank or partially completed manufacturing data”. On March 8, 2017, Qinhuangdao Zizhu Pharmaceutical was placed on import alert by the USFDA. Click here for our compilation of all non-compliances in 2017 (Excel version available) for FREE! Almost a year prior to the USFDA inspection, in October 2015, the company had been inspected by a WHO Prequalification Team (PQT) for levonorgestrel, mifepristone and ethinylestradiol APIs. The inspection found “five major deficiencies including data integrity issues and several minor deficiencies”. The WHO, however, went ahead and closed its inspection as compliant, based on corrective and preventive actions (CAPAs) provided by the manufacturer. In view of the USFDA actions, and the fact that Qinhuangdao Zizhu Pharmaceutical is the only WHO-PQT prequalified source of levonorgestrel API (as was seen in a similar case at Mylan), the WHO approach towards the compliance position was to focus extensively on product quality. READ: FDA and EU differ on cGMP standards at the same facilities: How will they mutually recognize inspections? Our view As the US regulators push hundreds of new generic drugs to market in an effort to drive down prices of generic drugs in the United States, the industry should get ready for an increasing number of inspections in the coming years. Our compilation indicates that in 2017, while most companies had installed the infrastructure necessary to combat issues related to data-integrity, there were problems that were systemic in nature. These ‘systemic problems’ remain, and the industry must get ready as the FDA and European inspectors join hands to crack down on them. PharmaCompass’ 2017 Recap of FDA Warning Letters, Import Alerts & EU Non-Compliances is an easy way to evaluate companies that have run into compliance challenges so that appropriate risk mitigation strategies can be adopted.

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11 Jan 2018

Amsterdam to host EMA; China pulls Skype out of app stores

This week in Phispers, we tell you how Amsterdam became EU’s choice for hosting the EMA. As Biocon receives an inspection closure from the FDA for its Bengaluru sterile injectables facility, we analyze how news reports on Biocon and Mylan moving a step closure to getting an FDA nod for its Herceptin biosimilar could be misplaced. We also bring you news on the positive trials from Roche and the Skype ban in China. Meanwhile, Concordia got into yet another drug price hike controversy. This time for its thyroid drug — liothyronine. Lucky draw gets Brexit-struck EMA a new home in Amsterdam The biggest news from the world of pharmaceuticals this week was the decision to relocate the European Medicines Agency (EMA), with nearly 900 employees, to Amsterdam (the Netherlands). The relocation of EMA from London is a consequence of the UK’s withdrawal from the European Union. The agency was not involved in the selection of the new location. Amsterdam was one of the 19 offers to host the EMA submitted by the EU member states at the end of July 2017. The EMA now has just over 16 months to prepare for the move and take up its operations in Amsterdam by March 30, 2019. “Amsterdam ticks many of our boxes,” Guido Rasi, executive director, EMA said. “It offers excellent connectivity and a building that can be shaped according to our needs,” Rasi added. The decision was made by closed ballot votes from each EU member state held in Brussels this week. An EMA survey of its staff found most of them might quit if posted to the bloc’s poor eastern regions. The employees had rated Amsterdam, Barcelona and Vienna as the top choices, while Warsaw, Poland, Bucharest, Romania, and Sofia, Bulgaria were rated the lowest. Milan, Amsterdam and Barcelona campaigned hard. But there was a push from eastern states, as Slovak capital Bratislava turned out to be a strong contender. In the first round, Milan (with 25 votes), Copenhagen and Amsterdam (with 20 votes each) advanced out. Bratislava had 15 votes and Barcelona had 12 votes. Milan (with 12 votes) and Amsterdam (with 9 votes) then proceeded into the third round of voting. In the final round of voting, Milan and Amsterdam both tied with 13 votes each. The decision was taken through a draw of lots, that Amsterdam won. Biocon gets EIR for sterile injectables facility; FDA nod for its biosimilar still in question India’s Biocon has received an EIR (establishment inspection closure) for its sterile injectables facility, inspected by the US Food and Drug Administration (FDA) earlier this year. However, contrary to what some recent news reports suggest, the company and its partner Mylan are not a step closer to getting an FDA nod for its biosimilar of Roche’s blockbuster cancer drug — Herceptin. According to these reports, Biocon and Mylan have resolved FDA concerns about its Bommasandra plant, setting it and Mylan up to potentially win FDA approval for the first Herceptin biosimilar. According to PharmaCompass’ analysis, there were two inspections at Biocon — the first one was for the biosimilars (during March 27 to April 7 this year); while the second one was for their sterile injectables facility (during May 25 to June 3 this year). Based on the dates shared in Biocon’s statement, the EIR is for the second inspection and there is no ‘exact’ news on the biosimilars inspection. The location of both inspections is the same — Plot 2-4, Phase IV, in Bommasandra, Bengaluru. However, there maybe different buildings within the campus that were inspected by the FDA. The same location in Bommasandra was also put on Health Canada’s Inspection Tracker list for data-integrity concerns found by a regulatory partner of Health Canada. According to news reports, the FDA EIR to the sterile plant comes less than two weeks before the December 3 date that the FDA has set for considering approval of the Herceptin biosimilar. The original action date was September 3, but the FDA delayed that for three months after seeking additional information from Mylan and Biocon. However, in our view, the EIR and the December 3 date have no correlation. After receiving the EIR, the FDA further indicated that Biocon needs to implement the CAPA (corrective action and preventive action) plan and resubmit the updated details. Meanwhile, Roche is using all its might to prevent its revenues from getting chewed away by cheaper biosimilars. This week, Roche Holding sued Pfizer Inc to stop it from selling a copy of Herceptin in the US. Boehringer opens the door for crowdsourced research through opnMe.com Germany’s Boehringer Ingelheim has launched opnMe.com — a platform that offers free and open access to certain pre-clinical molecules and non-clinical investigation to scientists worldwide. The opnMe.com platform provides scientists with many best-in-class molecules supported by comprehensive data packages on one centralized platform. It also offers them direct access to molecules for independent research as well as other molecules for partnering with Boehringer. Through opnMe.com, molecules for some of the most relevant targets in biomedical research would be shared. This, in turn, would create possibilities for further independent and collaborative discovery as well as the identification of novel treatment approaches for patients. “Working together with scientists across the world, we can accelerate research in a wide range of biomedical research areas,” Clive R. Wood, PhD, senior corporate vice president, Discovery Research at Boehringer Ingelheim, said. This launch is part of the German research-based pharma company’s ongoing mission to further scientific research and medical progress through collaboration and innovation. Roche’s shares surge after two trial wins of its potential blockbuster drugs Roche, which has been plagued by shrinking revenues from its older medicines, got a shot in the arm this week with two trial wins for its cancer (Tecentriq) and hemophilia (Hemlibra) drugs. The two drugs are potential blockbusters. Expectedly, Roche shares surged by 6.5 percent on Monday. This added more than US$ 12 billion to the company’s market capitalization. With Tecentriq, in combination with Avastin and chemotherapy, Roche has posted significant gains for progression-free survival and risk of death for a segment of lung cancer patients. Hemophilia agent Hemlibra, on the other hand, had reduced bleeds in a new group of patients. Tecentriq and Hemlibra, along with Roche’s multiple sclerosis medicine Ocrevus, are pillars of CEO Severin Schwan’s strategy that would offset the patent expiry of its top-selling drugs — Rituxan, Avastin and Herceptin. Together, these three drugs account for US$ 20 billion in annual sales. Since lung cancer is the largest oncology market, Roche’s trial of Tecentriq, in combination with Avastin and chemo, has been closely observed. With this drug, Roche seeks to compete with rivals in cancer immunotherapy. The mixture “provided a statistically significant and clinically meaningful reduction” in the risk of the disease worsening or death compared to Avastin plus chemotherapy in first-line treatment of advanced non-squamous non-small cell lung cancer (NSCLC), Roche said. Concordia’s thyroid drug caught in price hike controversy in the UK Last month, PharmaCompass had reported on a popular thyroid drug levothyroxine receiving several complaints of severe side effects from patients in France. The drug works as a stand-in for the hormone thyroxine in patients suffering from hypothyroidism, a condition that affects the body’s metabolism. And this week, Concordia Healthcare’s thyroid drug — liothyronine — got caught in a drug price hike controversy. An antitrust probe in the UK into Concordia’s pricing for liothyronine has found that the drug is now 57 times more expensive than it was in 2006. Both the thyroid drugs are different compounds — while liothyronine is the synthetic form of T3-triiodothyronine, levothyroxine is the manufactured form of T4-thyroxin. Physicians use liothyronine instead of or in addition to levothyroxine for patients undergoing thyroid hormone withdrawal. Concordia Healthcare has caught the ire of watchdogs even earlier for hikes in their drug prices. This matter only adds to the ongoing investigations. The UK Competition and Markets Authority (CMA) recently levied its biggest fine ever against Pfizer and Flynn Pharma, for driving up the price of an epilepsy drug. The fine is currently under appeal. “Pharmaceutical companies which abuse their position and overcharge for drugs are forcing the NHS—and the UK taxpayer—to pay over the odds for important medical treatments,” CMA chief Andrea Coscelli said in a statement. “We allege that Concordia used its market dominance in the supply of liothyronine tablets to do exactly that.” According to a statement provided to the Financial Times, Concordia said the pricing of liothyronine has been “conducted openly and transparently with the Department of Health in the UK over a period of 10 years.” Drug industry in China hit by local law that pulls Skype out from app stores Like several other industries, the pharmaceutical industry relies heavily on Microsoft’s Skype to communicate with its business partners. But this telecommunications application can no longer be downloaded in China, as Skype has been removed from both the Apple and Android app stores there. Apple said it is one of the several voice over internet protocol (VoIP) apps which was found not to comply with the local law by the Chinese government. Microsoft told the BBC that the app had been “temporarily removed” and the company was “working to reinstate the app as soon as possible”. China has increased scrutiny of internet applications this year, ordering firms to remove hundreds of apps that allow users to communicate confidentially or get around China’s so-called ‘great firewall system of censorship’ to use overseas social media. According to Reuters, over the last two months, authorities have also periodically interrupted services of Facebook Inc’s encrypted messenger app WhatsApp. Alphabet’s Google, Facebook and Twitter are unavailable to Chinese users. According to news reports, downloaded Skype apps continue to operate. However, users will not be able to update them.

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23 Nov 2017

Axovant’s hyped Alzheimer’s drug fails trial as Pfizer emulates Axovant; Amneal and Impax in merger talks

This week in Phispers, we bring you news about intepirdine, Axovant’s experimental drug for Alzheimer’s disease, on which both patients and investors had vested much faith. The drug failed primary endpoints. Meanwhile, Pfizer is emulating the Axovant strategy as it split four of its clinical-stage orphan drugs into a new company. There was more bad news for Biocon-Mylan, as Amgen filed a patent infringement case against Mylan in the US. Novartis’ new CEO says it will reduce the development cost of drugs by relying on data science. And, there is news on NASH drugs and on merger talks between Amneal and Impax Labs. Axovant disappoints investors; its Alzheimer’s drug fails primary endpoints After two years of brouhaha by investors, Axovant’s experimental drug intepirdine, as a treatment for mild to moderate Alzheimer’s disease, turned out to be a damp squib. The experimental drug did not meet its co-primary efficacy endpoints, a press release issued by Axovant said. The medicine turned out to be no different from 99 percent of medicines tested against Alzheimer’s. Investors had poured millions of dollars into Axovant. According to an estimate compiled by Bloomberg, intepirdine was expected to generate more than US$ 2 billion in sales for Axovant by 2023. But that was not to be. At 24 weeks, patients treated with 35 mg of intepirdine did not improve on either of two surveys — the Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and the Alzheimer’s Disease Cooperative Study-Activities of Daily Living scale (ADCS-ADL) — compared to patients treated with placebo. Back in 2015, Axovant — a company founded by Vivek Ramaswamy — had bought intepirdine from GlaxoSmithKline for US$ 5 million and launched Axovant’s US$ 315 million IPO around the drug. That’s when PharmaCompass had raised the question — has 29 year-old Ramaswamy shown GlaxoSmithKline that it made a billion dollar mistake by selling of its old Alzheimer drug to him? In April this year, Ramaswamy stepped down as CEO of Axovant by appointing former chief executive of Medivation, David Hung, in his place. Medivation got sold to Pfizer for US$ 14.3 billion last year. Last month, Ramaswamy’s Roivant (Axovant’s biggest shareholder) raised US$ 1.1 billion from big investors lead by Softbank’s Vision Fund. Roivant also raised millions of dollars from hedge funds like Viking Global Investors. These investments diluted the stakes of Ramaswamy and other initial investors in Roivant. But Ramaswamy is laughing all the way to the bank. Through divestments, he has secured a war chest for Roivant, which has been spinning out new companies with names ending with ‘vant’ — such as Axovant (neurology), Myovant (women's health and endocrine diseases), Dermavant (dermatology), Enzyvant (rare diseases), and Urovant (urology). Pfizer emulates Axovant; Ibrance maybe a US$ 5 billion drug next year Even as Axovant’s intepirdine failed to meet primary endpoints, the American pharmaceutical behemoth Pfizer seems to have taken a leaf out of its strategy book. Pfizer’s R&D strategy executive Lara Sullivan gained the company’s support to split four of its clinical-stage orphans into a new company called SpringWorks Therapeutics. And much like Axovant, Pfizer too is starting out with a mega-round of US$ 103 million in venture capital funding. SpringWorks is getting considerable financial support from Pfizer and funds like Bain Capital Life Sciences, Bain Capital Double Impact, Orbimed and LifeArc. Pfizer has spent US$ 24 billion over the past three years on R&D, the third highest R&D spend amongst pharma companies. Along with drug-focused acquisitions, Pfizer has spent US$ 43 billion in the same period. Ibrance to brighten up Pfizer’s fortunes: Meanwhile, Pfizer’s breast cancer drug Ibrance now competes with Novartis’ Kisqali. It will also compete with Lilly’s forthcoming drug abemaciclib. Though side effects are an issue for all the three drugs, Ibrance is expected to brighten up Pfizer’s fortunes. According to Morgan Stanley, Ibrance could bring in sales of US$ 939 million in the third quarter and US$ 1 billion in the fourth quarter, leading to US$ 3.5 billion in sales for 2017. And in 2018, Ibrance could fetch US$ 4.85 billion in sales. Novartis vows to slash drug development costs, while FDA terms system ‘broken’ The time and cost of taking a medicine from discovery to market has for long been seen as a drag on the pharmaceutical industry’s performance. The process has been estimated to take up to 14 years and cost at least US$ 2.5 billion. Last week, Janet Woodcock, director of FDA’s Center for Drug Evaluation and Research, said the clinical trials system is “broken” and there needs to be new ways to collect and utilize patient data. She was speaking at a workshop on real world evidence (RWE) at the National Academies of Sciences, Engineering, and Medicine. This week, the incoming chief executive of Novartis, Vas Narasimhan, has vowed to slash drug development costs, and save up to 25 per cent on multibillion-dollar clinical trials as part of a “productivity revolution” at the company. Quoting analysts, Narasimhan said between 10 and 25 per cent of trial costs could be reduced if digital technology were used to carry them out more efficiently. The Swiss drug major has 200 drug development projects under way and is running 500 trials. Therefore, digital technology “will have a big effect if we can do it at scale,” he added. Narasimhan plans to partner with, or acquire, artificial intelligence and data analytics companies, to supplement Novartis’s strong but “scattered” data science capability. After Pfizer, Takeda may soon exit Brazil; seeks suitors for Multilab Not long ago, Brazil was one of the hottest emerging markets for drugs, and big pharma were lining up to cash in on this opportunity. Today, Brazil is in the midst of a historic recession that has dampened drug demand. In July this year, Pfizer relinquished its 40 percent stake in the Brazilian generic drug firm — Laboratório Teuto Brasileiro — for a paltry 1 Brazilian Real (or US$ 0.30) to the heirs of the company. Pfizer had acquired the stake for US$ 240 million back in 2010. And this month, it looks like Japan's largest pharmaceutical company Takeda is following Pfizer’s footsteps and is going to dispose off its 2012 acquisition of Multilab laboratory (which it had acquired for Brazilian Real 500 million or US$ 158 million). According to news reports, Takeda may recover only a fifth of its original investment (of Brazilian Real 100 million or US$ 31.57 million). Takeda is expected to receive proposals for Multilab from mutual funds and domestic companies with similar business interests. FDA issues warning on Ocaliva (obeticholic acid) use; Allergan’s NASH drug also stumbles The US FDA issued a warning as 19 patients died after taking Intercept’s liver disease drug Ocaliva. The company responded by saying the dosing administered was incorrect. In most cases, the exact cause of death wasn’t known. But seven of the patients who died were taking Ocaliva more frequently than recommended, the FDA said. Earlier this month, Intercept had warned doctors that Ocaliva can cause injuries, organ failure, or death if it’s not used exactly as intended in patients with primary biliary cholangitis, a relatively rare liver condition for which the drug was approved last year. The company says it is working with the FDA on revised labeling aimed at more clearly indicating the recommended dosing regimen for all patients. Intercept is in the final stages of testing Ocaliva for nonalcoholic steatohepatitis, or NASH, a silent disease in which the liver gets inflamed and damaged due to a buildup of fat. Dozens of pharma companies including Gilead Sciences, Allergan and Intercept Pharmaceuticals are trying to develop a treatment for the disease. Over the last two years, at least six deals valued at US$ 3.52 billion or more have taken place involving drugs that target various aspects of NASH. Meanwhile, Allergan’s Cenicriviroc (CVC) showed mixed results in a Phase 2b clinical trial. CVC is facing trials for the treatment of liver fibrosis in adult NASH patients. The trial involved a two-year study. According to Seeking Pharma, 20 percent of patients in the placebo arm during year one who crossed over to receive CVC during year two achieved the combined endpoint of reduction in fibrosis by at least one stage and no worsening of NASH compared to 13 percent for those who continued on placebo. However, “there was no difference between CVC and placebo in patients who remained on treatment for two years as determined by the composite endpoint,” it added. Another setback for Biocon/Mylan, as Amgen files patent infringement case in US News doesn’t seem to be getting better for the Biocon/Mylan combine. First, they withdrew their applications for the trastuzumab and pegfilgrastim biosimilars from Europe. And then, the FDA extended the target action date for their trastuzumab biosimilar. Now, the duo will be facing Amgen in court to defend themselves in a patent infringement case. Last week, Amgen filed a complaint for patent infringement under the Biologics Price Competition Innovation Act (BPCIA) against Mylan, which is developing a biosimilar of its drug Neulasta (pegfilgrastim). Approval delays, spiraling compliance costs and now litigation expenses won’t help the profitability of Mylan-Biocon’s endeavors. In Europe, competition is already moving ahead as the EMA’s Committee for Medicinal Products for Human Use recommended the approval of Samsung’s Herceptin-referencing biosimilar Ontruzant. This is the fourth patent litigation under the BPCIA regarding a proposed biosimilar of Neulasta, none of which are yet FDA-approved. Amneal in merger talks with Impax Laboratories Analysts have been predicting a consolidation in the world of generics. According to reports, Impax is in merger talks with generics competitor Amneal Pharmaceuticals. The deal would value Impax at US$ 2 billion or more. According to FiercePharma, the talks could result in a deal next month. Impax is headed by Paul Bisaro (who quit Allergan to join Impax in March this year). He has considerable experience in M&As. Last year, Bisaro sold off part of Allergan’s business to Teva Pharmaceuticals in a US$ 40.5 billion deal. And last month, Shanghai Fosun Pharmaceutical picked up a 5.2 percent stake in Impax. Amneal, on the other hand, is owned by Chintu and Chirag Patel.

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28 Sep 2017

Pfizer sues J&J; Generics under pressure; China’s Fosun resurrects deal to buyout India’s Gland

This week, Phispers brings you news on how a federal judge in the US revoked ‘pharma bro’ Martin Shkreli’s bail due to his misconduct on Facebook. Roche, the world leader in oncology treatments, has to contend with more competition from biosimilars, as Amgen and Allergan’s Avastin copy bags USFDA approval. China’s Fosun Pharma tweaked its Gland Pharma buyout deal in order to avoid a review by the Indian government. And, Teva starts selling assets to reduce its debt burden. Shkreli finally sees jail for putting a bounty on Hillary Clinton’s hair Martin Shkreli, former CEO of Turing Pharmaceutical, an entrepreneur and the founder of several hedge funds, was sent to jail last week, not for the financial frauds or for raising the sticker price of a life-saving drug (Daraprim) by 5,000 percent in 2015, but for offering US$ 5,000 for a strand of Hillary Clinton’s hair. The federal judge revoked his bail due to this misconduct on social media. Shkreli has been on a US$ 5 million bail, even as he is awaiting sentencing. He made two Facebook posts offering cash to anyone who could “grab a hair” from Clinton during her book tour. Shkreli has branded himself as one of social media’s ‘most notorious trolls’. At the hearing in Brooklyn, the judge said Shkreli’s post could be perceived as a threat. And now, Shkreli (34), who called his post satire, is cooling his heels at the Metropolitan Detention Centre in Brooklyn. Last month, Shkreli was convicted in three out of eight charges, including securities fraud. He was scheduled to be sentenced on January 16. Unless his lawyers prove he poses no threat to the community, Shkreli is not likely to be released from jail. China’s Fosun resurrects deal to buyout Gland by scaling down stake purchase Shanghai Fosun Pharmaceutical Group has reduced the amount of stake it wishes to buy into Indian drugmaker Gland Pharma from 86 percent to 74 percent, in order to avoid a review by the Indian government. This way, Fosun is potentially resurrecting a transaction that had been on hold for over a year. Backed by Chinese billionaire Guo Guangchang, Fosun Pharma will now buy 74 percent stake in Gland for US$ 1.09 billion, Fosun said in a statement to the stock exchanges. In June 2016, the Indian government had changed regulations pertaining to foreign direct investment (FDI) in existing pharmaceutical firms through the automatic route. Under the new rules, FDI involving more than 74 percent stake now requires an approval by the Indian government. The previous move, to buy 86 percent stake in Gland, would have required an approval by the Cabinet Committee on Economic Affairs (CCEA). The proposal was not taken up by the CCEA and was subsequently put in cold storage during the Doklam tensions between India and China. Hyderabad-based Gland specializes in injectable drugs such as antibiotics, oncology and cardiology treatments. Gland’s manufacturing facilities have been accepted by the US Food and Drug Administration (USFDA) and other regulatory agencies. The deal would give the Chinese firm access to Gland’s portfolio of generic injectable medicines and control of facilities to export to the US and other developed markets. The original acquisition offer (for 86 percent stake) valued Gland at about US$ 1.35 billion. The firm has also delayed the closing date for the deal to October 3, from September 26. Rise of biosimilars: Pfizer sues J&J; Roche faces more heat from biosimilars This week, Pfizer filed a lawsuit against Johnson & Johnson (J&J), alleging that J&J's contracts with health insurers for its blockbuster rheumatoid arthritis drug, Remicade, were anticompetitive and blocked sales of Pfizer’s newly-approved biosimilar (known as Inflectra). According to Pfizer, J&J has signed exclusionary contracts with health insurers, hospitals and doctor groups which exclude Pfizer’s Inflectra from insurance coverage. In the first quarter of 2017, J&J’s chief financial officer had mentioned that they saw “very little impact” from biosimilar competition to Remicade in the US. Roche, the world’s biggest maker of oncology treatments, also has more biosimilars to contend with. In the US, the FDA gave its nod to Mvasi (bevacizumab-awwb) as a biosimilar to Avastin (bevacizumab) for the treatment of multiple types of cancer. Mvasi is the first anti-cancer biosimilar approved by the USFDA. Amgen and Allergan’s bevacizumab biosimilar is also undergoing review by the European Medicines Agency (EMA). The companies are collaborating on the development and commercialization of four oncology biosimilars. Roche received another blow last week, when the EMA’s Committee for Medicinal Products for Human Use recommended the approval of Samsung’s Herceptin-referencing biosimilar Ontruzant. It is the first biosimilar copy of Herceptin to obtain such a backing in Europe. In June this year, the European Commission had approved Rixathon — a biosimilar for Roche’s MabThera (or Rituximab, a drug for blood cancer). These approvals are expected to herald in a gradual erosion in sales of patented cancer drugs. Rituximab, Herceptin and Avastin together had 2016 revenue of US$ 21.8 billion. But their combined sales are expected to fall more than 40 percent by 2022, says a forecast compiled by Thomson Reuters. Roche needs to offset this ‘anticipated’ drop in sales by making a success of its new cancer drugs, such as Perjeta, Gazyva and Tecentriq. Biosimilars (medicines that are highly similar to the original drug) offer a route to more affordable cancer care at a time when the price of modern therapies to fight tumors is going through the roof. Generics under pressure: Teva sells assets to reduce debt; new M&A head at Lupin Last week, there was finally some good news from Teva Pharmaceutical Industries, when it announced the name of Kare Schultz as its new CEO. Soon after that, the Israeli drugmaker announced it has sold its Paragard intrauterine copper contraceptive to CooperSurgical for US$ 1.1 billion in cash in order to bring down its debt load. Teva will also sell the remaining assets in its specialty women’s health business for US$ 1.38 billion in two separate transactions. CVC Capital Partners Fund VI will pay US$ 703 million in cash for a portfolio in Teva’s global women’s health business including contraception, fertility, menopause and osteoporosis products. Teva also agreed to sell its Plan B One-Step and its brands of emergency contraception to Foundation Consumer Healthcare for US$ 675 million in cash. Combined annual net sales of these products were US$ 140 million last year. However, even after these sales, Teva will continue to remain highly indebted. Last year, Teva had purchased Allergan’s generic unit for US$ 40.5 billion, taking its debt load to US$ 35 billion. Teva is actively pursuing divestitures and expects to garner at least $2 billion in total asset sales for the year. Meanwhile, Mumbai-headquartered Lupin has hired Jim Loerop to drive its global M&A strategy. He will also lead Lupin’s overall corporate development efforts, besides being responsible for its M&A and business development functions. Loerop joins Lupin from Alexion Pharmaceuticals. FDA wants more compounding pharmacies to register under law The USFDA Commissioner Scott Gottlieb said the agency is working on a new policy that would encourage more compounding pharmacies to register under a law enacted in the wake of a deadly 2012 meningitis outbreak linked to one such company. The traditional role of compounding pharmacies is to make drugs prescribed by doctors for specific patients with needs that can’t be met by commercially available drugs. Back in 2012, a compounding pharmacy known as the New England Compounding Center (NECC) had triggered a meningitis outbreak by using contaminated steroids. NECC is now defunct. But prosecutors are preparing for the second criminal trial over contaminated steroids manufactured by NECC. Glenn Chin, a former supervisory pharmacist at NECC, is facing trial this week for second-degree murder and fraud. He has pleaded not guilty. The 2012 meningitis outbreak had affected 778 patients across the US, out of which 76 had died after receiving contaminated steroids. After the outbreak, the US had passed the Drug Quality and Security Act in 2013, which aimed to bring more compounding pharmacies under the FDA (rather than under the state pharmacy boards). The law created a category of “outsourcing facilities” that could register with the FDA, allowing them to sell products in bulk to hospitals and physician practices without prescriptions for individual patients. Today, around 70 firms have registered as outsourcing facilities. According to the American Pharmacists Association, there are about 7,500 pharmacies that specialize in compounding services. Gottlieb said in order to encourage more compounders to register, the FDA would release draft guidance in the next two months. FDA nod for GSK’s triple drug inhaler for COPD puts it ahead of rivals The USFDA has approved British pharma giant GlaxoSmithKline’s three-in-one inhaler — Trelegy Ellipta — for chronic obstructive pulmonary disease (COPD). This is a key new product for GSK as it strives to keep its lead in respiratory medicine, despite falling sales of Advair (an asthma and COPD treatment). Trelegy Ellipta is the first once-daily triple medicine for COPD. The inhaler puts GSK ahead of rivals such as AstraZeneca and Novartis. GSK developed this inhaler along with Innoviva, an American drug company. Last week, the inhaler, also won a recommendation for approval from the EMA. GSK’s CEO Emma Walmsley sees Trelegy Ellipta as one of three “critical” launches that would fill in the revenue gap left by the sagging sales of Advair, which is expected to face generic competition in the US sometime next year. Walmsley’s other two key new products are Shingrix, a shingles vaccine that was unanimously recommended for approval by a USFDA advisory panel last week, and a novel dual-drug regimen for HIV.

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21 Sep 2017

FDA to share full inspection reports with EU; Difficult week for Teva, J&J, Mylan

This week, Phispers brings you the latest from the world of biosimilars, with Samsung Bioepis tying up with Japan’s Takeda, Biocon transferring its biosimilar business to a subsidiary, and South Korea’s Celltrion denying reports that its proposed biosimilar of Herceptin could face delays in Europe. Teva faced yet another bad week, with two Congressmen in the US attacking it over price increases of its multiple sclerosis drug. Meanwhile, Mylan and J&J will have to pay millions of dollars for cases against them. In vaccines, GSK faces flak for shortage of its Hepatitis B vaccine in the UK. And Pfizer won a pneumonia vaccine patent battle in India. Biocon transfers biosimilar business to subsidiary; Samsung Bioepis ties up with Takeda A lot has been going on in the world of biosimilars. Last week, in a stock exchange filing, Biocon said it has withdrawn the dossier for the biosimilar products — Fulphila® (pegfilgrastim) and Ogivri® (trastuzumab). Since the approval of its trastuzumab and pegfilgrastim applications would require re-inspection of its drug product facility (for these products), the “request of withdrawal of the dossiers and re-submission is part of the EMA procedural requirements linked to this reinspection…,” Biocon said in the statement. The announcement came a fortnight before the FDA was supposed to take a decision on the trastuzumab application. This week, the board of Biocon approved the transfer of the biosimilar business of the company to Biocon Biologics India, a step-down subsidiary of the company, subject to the consent of its shareholders. The transfer of the biosimilar business has been done by way of a ‘slump sale’ as a going concern — wherein a sale is done for a lump sum consideration without values being assigned to the individual assets and liabilities. Concerns also emerged over Biocon’s Herceptin biosimilar competitor — Celltrion — as it denied a news report that its proposed biosimilar of Herceptin (a breast cancer drug) could face delayed European approval due to late submission of data. With global sales of around US$ 7 billion a year, Herceptin is one of Roche’s best-selling drugs. According to the Celltrion, the European Medicines Agency (EMA) found no lapses during a pre-approval inspection of its product site and drug substance Herzuma — its copy version of Roche’s Herceptin. The South Korea-headquartered biopharmaceutical firm also managed to hand in the documents that it was required to provide after inspection. “We don’t expect any major changes in approval procedures although the inspection date had been pushed back a little because of differing schedules,” a Celltrion official said. There was news that the EMA could postpone approval of Herzuma to 2018 as the company failed to submit documents on time. However, it seems like Celltrion’s Herzuma may get EMA’s nod this autumn. Any delays in approval procedures for Herceptin biosimilar candidates could have an impact on other drug makers eyeing the US$ 2 billion EU market for the original drug including another South Korean biosimilar firm — Samsung Bioepis — which filed for EU approval in September 2016. The biosimilar industry is keeping a close watch on which of the two South Korean firms is the first to get the nod for its Herceptin biosimilar, after Biocon withdrew its application last week. Meanwhile, Samsung Bioepis unveiled a new alliance this week — with Japan’s Takeda. Together with Takeda, Samsung Bioepis hopes to accelerate the development of effective therapies. The Japanese firm has been open to devising new alliances that will share the risk in order to broaden its overall drug development work. More bad news for Teva as US Congressmen attack pricing of its flagship therapy Two US Congressmen accused Teva of hiking the price of its flagship multiple sclerosis (MS) drug — Copaxone (glatiramer acetate) — by more than 1,000 percent since 1996. Copaxone generated US$ 4.22 billion in sales last year. The Congressmen — Elijah Cummings and Peter Welch — want to fully investigate Teva’s pricing practices, while also calling out firms such as Novartis, Bayer and Biogen. According to the Congressmen, a year’s worth of 20 mg Copaxone was priced at US$ 8,292 in 1996. This increased to US$ 51,315 in 2012 and US$ 91,401 in 2017. Lack of generic competition permitted Teva to increase the price of the drug to such high levels. Cummings and Welch said they were launching an investigation into why prices for MS treatments have nearly quintupled since 2004. According to the National Multiple Sclerosis Society, the average annual cost of MS therapy rose to US$ 78,000 in 2016 from US$ 16,000 in 2004. Meanwhile, Teva is planning to tie up with other drugmakers to fund some of its development pipeline as it struggles with debts and expiring patents. Teva needs funds to develop new drugs, and striking alliances with big pharma players is one way of doing that. Earlier this month, Teva reported a steep drop in second-quarter earnings. Teva is saddled with debts of around US$ 35 billion, which it took on when it acquired Actavis (Allergan’s generic business) for US$ 40.5 billion last year. Sanofi gains millions via Mylan’s EpiPen settlement; J&J to pay US$ 417 million in baby powder case Last week, Mylan NV and the US Justice Department finalized a US$ 465 million settlement to resolve claims that Mylan had defrauded taxpayers and overcharged the government by misclassifying its EpiPen emergency allergy treatment as a generic drug. EpiPen had become the center of a drug price-hikes controversy last year. The probe into the price of EpiPen followed a whistleblower lawsuit filed under the False Claims Act that rival drugmaker Sanofi SA filed in 2016. As a result of the settlement, Sanofi will receive US$ 38.7 million as a reward, authorities said. Meanwhile, lawmakers in the US say the settlement wasn’t tough enough. According to Democratic Senator Richard Blumenthal of Connecticut, the agreement was a “feeble fraction” of the US$ 1.27 billion that a government report found taxpayers may have overpaid for EpiPen over the last decade. Mylan had acquired EpiPen in 2007. It is a handheld device that treats life-threatening allergic reactions by automatically injecting a dose of epinephrine. Mylan had raised the price of a pair of EpiPens to US$ 600, from US$ 100 in 2008. J&J baby powder case: A US court directed Johnson & Johnson to pay US$ 417 million to a woman who alleged that the company’s baby powder causes ovarian cancer. In her lawsuit, 63-year-old Eva Echeverria had claimed that she used the talcum powder from the 1950s till 2016, and developed ovarian cancer in 2007. Echeverria alleged that J&J failed to warn consumers about the risks involved in using their talcum powder. The court awarded the woman US$ 68 million as compensatory damages, and US$ 340 million as punitive damages. Hikma raises price of diarrhea drug by 400 percent; Trump signs user fee law Last week, the US saw another price-gouging incident. The US subsidiary of Hikma Pharmaceuticals Plc raised the price of a common diarrhea drug by more than 400 percent. Known as West-Ward Pharmaceuticals, the US division of Hikma is also charging more for five other medicines. According to a Financial Times report, the average wholesale price of a 60 ml bottle of liquid atropine-diphenoxylate, a common diarrhea drug also known as Lomotil, went from about US$ 16 a bottle to US$ 84. FDA Reauthorization Act: Last week, President Donald Trump signed the FDA Reauthorization Act of 2017 into law. With this, the FDA saw the end of a two-year long process that was threatening to disrupt its operations. The law comes at a time when the FDA, under the new commissioner Scott Gottlieb, is approving generics at a record pace. Though the legislation had been passed by both the houses of the Congress, it faced a number of threats, including Trump’s intent to fund the FDA entirely with user fees from companies. Between 2018 and 2022, the FDA is expected to collect US$ 9 billion in fees — US$ 8 billion for prescription drugs and US$ 1 billion for devices — based on the fee level set in the Senate bill. GSK faces flak for Hep B vaccine shortage in UK; Pfizer wins vaccine patent in India In the UK, drug giant GlaxoSmithKline faced flak and an increasing number of questions over shortages of its vaccine for the deadly liver disease hepatitis B. The shortage of this vaccine in the UK has led to rationing. Earlier this month, Public Health England (PHE) took the rare step of advising doctors to limit prescription of the vaccine, citing a “global shortage”. This comes at a time when GSK’s supplies of the vaccine to the US appear to be unaffected. The disparity has led to suggestions from liver disease campaigners that GSK may be “prioritizing” the massive American market. Hepatitis B is considered a “silent killer” leading to 900,000 global deaths a year. However, the disease is more prevalent in the developing world and is rare in the UK. Meanwhile, the World Health Organisation (WHO), has said there is no global shortage of the vaccine. The WHO is responsible for monitoring stocks of vaccines worldwide. In India, Pfizer Inc was granted a patent for its powerful pneumonia vaccine —Prevenar 13. The decision bars other companies from making cheaper copies of the vaccine and allows Pfizer to exclusively sell it in India until 2026. The patent came as a blow to some health groups that said this would put the treatment out of reach of thousands in poorer nations. The move comes at a time when India is facing increased pressure from the US to tighten its patent laws. In a report published in June this year, the United States Trade Representative expressed concerns over India’s intellectual property laws. India has the largest number of pneumonia cases, and for Pfizer, this is a big gain. The decision also has international implications, as several poorer nations rely on India’s robust pharmaceutical industry to supply cheaper copies of medicines and vaccines. FDA to start sharing full inspection reports with European regulators This week, the European Commission (EC), the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) signed a new confidentiality commitment that allows the FDA to share non-public and commercially confidential information, including trade secret information relating to inspections with European regulators. In March 2017, the United States and the European Union (EU) finally announced that they will be able to utilize each other’s good manufacturing practice (GMP) inspections of pharmaceutical manufacturing facilities. The deal is expected to enable the US Food and Drug Administration (FDA) and the EU to avoid duplication of drug inspections, lower inspection costs and enable regulators to devote more resources to other parts of the world where there may be greater risk. This confidentiality commitment is a step in the ongoing implementation of the mutual recognition of inspections program.

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24 Aug 2017

Dr. Reddy’s fails EU inspection; Trump disbands business councils after Merck CEO and others quit it over intolerance

This week, Phispers brings you the high-pitched drama from President Trump’s American Manufacturing Council, with Merck CEO Ken Frazier leading the pack of CEOs who abandoned it over the Charlottesville unrest, even as J&J’s CEO said he’ll stay on. But then, Trump disbanded the council. We bring you news on more generic companies in distress due to a drop in their business in the US and compliance problems. Meanwhile, companies like Intas and Aurobindo Pharma from India and Fosun from China are looking for growth via acquisitions. And Softbank has invested US$ 1.1 billion in Roivant. Read on. Merck CEO’s Trump council resignation over ‘intolerance’ has others follow; council disbanded The US President Donald Trump’s American Manufacturing Council has been in the news for the last few days. First, Merck CEO Kenneth Frazier resigned from the council, after urging American leaders to reject expressions of ‘hatred, bigotry and group supremacy’ on Twitter. In a statement, Trump had blamed “many sides” for the violence in Charlottesville, Virginia, over the last weekend. A white nationalist rally had turned violent in the city when a car rammed into many people who were protesting peacefully against the demonstration. White supremacists and other hate groups had assembled in the city to protest the removal of a statue of Confederate General Robert E. Lee. Trump has since faced widespread criticism for not specifically denouncing the white supremacists. Following Frazier’s resignation, many CEOs — including Intel Corp’s Brian Krzanich, Under Armour Inc’s Kevin Plank and AFL-CIO chief Richard Trumka — quit Trump’s council over his ‘response to the Charlottesville violence’. Though Frazier said he was taking a stand “against intolerance and extremism”, Trump mocked at him on Twitter, and said he will now “have more time to LOWER RIPOFF DRUG PRICES!” Later, Trump did condemn the hate groups, but it seemed too little to late. Only three weeks back, Trump had called Frazier a “business genius” and a “great, great business leader” and had thanked Merck for investing in American jobs. Frazier is one of the few African-Americans to head a Fortune 500 company. Meanwhile, on Tuesday, Johnson & Johnson’s CEO Alex Gorsky said he isn’t abandoning Trump’s council. In a statement, Gorsky said he’ll stick with the council as a way to express “the values of Our Credo as crucial public policy is discussed and developed.” He said J&J is “an important voice on healthcare.” However, as the CEO resignations continued to mount, Trump tweeted, “Rather than putting pressure on the business people of the Manufacturing Council & Strategy & Policy Forum, I am ending both. Thank you all!” Trump made the announcement on Twitter, less than an hour after one of the groups was planning to inform the White House that it would disband, a CNBC report said. Dr. Reddy’s fails EU GMP inspection; can’t export to EU until it clears next inspection Less than two months after providing positive inspection updates with regard to the status of its manufacturing compliance, Dr. Reddy’s Laboratories (DRL) failed a European cGMP manufacturing inspection last week. The inspection, by the German regulatory authority, at DRL’s FTO 2 finished formulation plant (situated in Hyderabad) uncovered critical deficiencies. The inspectors concluded that the ‘essential elements of the Pharmaceutical Quality System’ were not effective. Due to this, the plant will not be able to make any further dispatches to the European Union until the next inspection, “to be initiated by an invitation from betapharm,” DRL said in a filing. Betapharm Arzneimittel GmbH is DRL’s wholly-owned subsidiary in Germany and the Hyderabad plant produces tablets and capsules. Previously, PharmaCompass had observed that the inspection focus of regulators has moved beyond audit trails. In the case of DRL, the inspectors found that out of specification (OOS) results were “systematically invalidated in hundreds of cases”. The integrity of the batch manufacturing/packaging record at the Hyderabad facility was also questioned. The absence of recording “negative events” on the “clean” batch manufacturing records prevented successful investigation into market-complaints. In addition to the integrity of the cleaning being questioned, the design, condition and maintenance of rooms and equipment were also major concerns at DRL. The inspectors found dirty rooms and equipment, along with unsuitable doors and dispensing equipment for manufacturing. Generics in distress: Sun reports its first loss in 12 years; Mylan cuts forecast Generic drugmakers have seen their US businesses plummet as the US Food and Drug Administration (USFDA) has stepped up product approvals, ushering in more competition and prompting a steady erosion in prices. As a result, generic drug stocks have been under pressure. Last week, Phispers reported on how Teva Pharmaceutical had reduced its earnings goal. Well, companies like Mylan NV and Sun Pharmaceutical Industries have joined the pack by reporting lackluster quarterly results and cutting guidance. After a gap of 12 years or more, Sun Pharma reported its first quarterly loss last week, after it settled an antitrust case in the US. Sun Pharma paid US$ 148 million (INR 9.5 billion) to plaintiffs including Canadian rival Apotex in July to settle an antitrust lawsuit in the US over sleep-disorder drug modafinil. Sun, which is India’s biggest drugmaker, posted a total loss of US$ 66.3 million (INR 4.25 billion) in the three months ended June 30, 2017. Last week, Mylan also said it is likely to see a decline in its profitability due to delays in the launch of key new drugs and erosion in the prices for generics in the US. Though the FDA is speeding up generics approvals, it’s just not speeding up the ones that Mylan badly needs. Mylan said it plans to remove copies of big drugs like Copaxone from Teva and Advair from GlaxoSmithKline—from its 2017 guidance, pushing them into 2018. It now expects revenues to hit between US$ 11.5 billion and US$ 12.5 billion for the year, down from a previous range of US$ 12.25 billion to US$ 13.75 billion. Chip Davis, CEO of the Association of Accessible Medicines — a trade group for generic and biosimilar drugs — said some of the (demand-supply) imbalances in the generic marketplace haven’t happened overnight. But the “reality is that the sustainable, robust competitive market is at risk now.” He expects generic drugmakers to continue to feel the pressure, amid declining prices and flat revenues. From June 2016 to June 2017, the number of generic prescriptions is nearly flat, with an increase of only around 1 percent; while revenue is down 12 percent, Davis said. However, one generic company that bucked the trend was Perrigo. It reported US$ 1.24 billion in sales and adjusted earnings of US$ 1.22 per share, topping the consensus for US$ 1.18 billion and 92 cents, respectively. However, this performance too did not come on the back of generics — Perrigo’s generic business declined 13 percent year-on-year. The company performed well due to its consumer business. India’s Intas and Aurobindo, PE player SK Capital and China’s Fosun in acquisition mode Even during these bad times for generics, some pharma companies are on the prowl. For instance, Ahmedabad-based Intas Pharmaceuticals is on the look out for buying into a larger piece of Israeli-drugmaker Teva’s existing operations in Europe. Last year, it had bought out Teva’s UK and Ireland assets. Intas — with Temasek and Chrys Capital as its investors — is bidding for Teva’s women's health, oncology and pain management divisions in Europe for US$ 1.5 billion. The company has reportedly reached out to several Indian and global banks, such as ICICI, Axis, Citi, Bank of Tokyo Mitsubishi UFJ, HSBC among others, to finalize the financing before putting in a bid by the month-end. If successful, this will be the largest cross-border M&A involving an Indian pharma company. PharmaCompass has been routinely covering the troubles at Teva, the world’s largest maker of generic drugs. Teva plans to sell off its assets, in order to reduce its US$ 36 billion debt. There is another company that Intas has set its eyes on — Mallinckrodt's US generic business. According to a news report, India’s Aurobindo Pharma and Intas are in the race to buy UK-based Mallinckrodt’s generic drugs business in the US valued at US$ 2 billion. Once complete, this will be the biggest-ever overseas acquisition made by an Indian drug company. The generic business of Mallinckrodt generates sales of around US$ 1 billion. The companies have submitted an initial bid for Mallinckrodt’s generic business, which has been up for sale for the last couple of months. Meanwhile, US specialty drugmaker — Arbor Pharmaceuticals — too is up for grabs. And amongst the bidders for a stake in Arbor are companies like Fosun International Limited’s healthcare business and Shanghai Pharmaceuticals Holding. The two companies are competing to buy a stake of at least 20 to 30 percent, sources said. The holding in the Atlanta-based Arbor could fetch around US$ 600 to US$ 700 million. In the US, SK Capital, a private investment firm focused on specialty materials, chemicals and pharmaceuticals, said it has signed a definitive agreement to acquire Perrigo API, the active pharmaceutical ingredients (API) business of Perrigo Company Plc. The two parties have agreed to enter into a long-term supply agreement for Perrigo API to supply multiple existing commercial and pipeline APIs to Perrigo. The transaction is expected to close during the last quarter of this year. Softbank invests US$ 1.1 billion in Vivek Ramaswamy’s abandoned drug venture —Roivant Last week, Roivant Sciences announced that Japanese conglomerate — SoftBank Group — is leading a US$ 1.1 billion investment to fund its expansion. SoftBank is the largest private financier in healthcare. Roivant was founded by Vivek Ramaswamy, a 32-year old American entrepreneur who began his career as an investor in the biotechnology sector. Roivant is a holding company with companies like Axovant Sciences and Myovant Sciences under its umbrella, along with private-subsidiaries like Dermavant, Urovant and Enzyyant. According to Endpoints News, SoftBank’s US$ 1.1 billion mega-investment in Roivant won’t likely be its last in biotech. Quoting reports, it says SoftBank group’s global US$ 100 billion equity fund has begun a recruitment campaign for scientists with an eye to backing more companies that use new data technology to identify drugs with solid development potential. Ramaswamy’s business model has relied on therapies that have been taken off the shelves of some big players. Back in December 2014, Ramaswamy had bought an old Alzheimer’s drug that GSK had dropped for US$ 5 million. Six months after purchasing the compound from GSK, and without doing any clinical development, the drug resulted in the biggest biotech IPO ever for Axovant, which got valued at US$ 2 billion. Since then, Ramaswamy has been setting up more companies. Biocon, Mylan suffer another setback as European biosimilar applications are withdrawn Last month, PharmaCompass broke the story about Biocon’s biosimilar program suffering a serious setback as a current Good Manufacturing Practices (cGMP) inspection by the French health agency — ANSM — in March 2017 of its drug product site located in Bengaluru, India, uncovered 35 deficiencies, of which 11 were deemed major. The inspection was conducted on behalf of the European Medicines Agency (EMA) by the ANSM as a pre-approval inspection for the drug product manufacturing activities of the following (three) biosimilar products — Fulphila® (pegfilgrastim), Ogivri® (trastuzumab) and Semglee® (insulin glargine). This week, in a stock exchange filing, Biocon said it has withdrawn the dossier for two of these products. Since the approval of its trastuzumab and pegfilgrastim applications would require a re-inspection of its drug product facility (for these products), the “request of withdrawal of the dossiers and re-submission is part of the EMA procedural requirements linked to this reinspection…,” Biocon said in the statement. The announcement comes two weeks before the FDA is supposed to take a decision on the trastuzumab application. Although Roche’s European patents on Herceptin (trastuzumab) expired in 2014, it is still the third-biggest drug, with 2016 sales of US$ 6.7 billion (CHF 6.8 billion) for the Swiss Group. Until the news of the ANSM inspection surfaced, Mylan and Biocon were expected to be the first to bring a Herceptin biosimilar to market.

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17 Aug 2017

Trump tells FDA to fund itself fully through industry fees; Astra’s CEO dumps Teva offer

This week, Phispers brings you lots of regulatory news from the US, where the Trump administration has instructed FDA to fund itself entirely through industry fees; and the agency’s chief has pledged to accelerate generic reviews through two new policies. This was yet another bad week for Teva, as it faced charges in Europe, lost a patent battle in the US to Takeda, and AstraZeneca’s CEO reportedly tossed away an offer to head it. Plus, there is news on AstraZeneca’s investment in China and Novartis’ CAR-T cell therapy for cancer. Teva’s woes continue: Faces EC charges; loses patent battle; and Soriot drops offer Teva’s troubles continued unabated. First, Pascal Soriot, the chief executive of AstraZeneca, who was rumored to be the next head of the Israeli drugmaker, decided not to leave AstraZeneca. He is reportedly forgoing an offer of a US$ 20 million bonus, and a chance to reorganize Teva, the world’s largest generic drug company. Last week, the UK-based drug firm confirmed that Soriot would be presenting AstraZeneca’s second-quarter earnings, on July 27. Rumors of Soriot’s likely appointment were floated by an Israeli financial website. Teva is likely to announce the name of its new CEO within a month, Chaim Hurvitz, a member of Teva’s founding family, said. Second, the European Commission (EC) charged Teva of doing an illegal deal with Cephalon to delay selling a cheaper generic version of Cephalon’s sleep disorder drug. In the past, the EU regulator has charged scores of other companies as well, including Denmark’s Lundbeck, USA’s Johnson & Johnson and France’s Servier. According to the regulator, the pay-for-delay deals cost European consumers billions of euros. Third, the Israeli pharma biggie lost a patent battle in the US appeals court to Takeda Pharmaceutical. The court said a patent on Takeda's cancer treatment — Velcade — is valid, pushing back the date when generic drug makers, including Teva and Mylan, will be allowed to launch lower-cost versions of the drug in the US. AZ invests US$ 79 million in Australia to cater to China’s demand for asthma drug Air pollution is choking people in the big cities of China, raising demand for AstraZeneca’s asthma medicine — Pulmicort respules. As a result, the British pharmaceutical giant announced an investment of US$ 79.27 million (AUD $100 million) last week at its Sydney site which manufactures the treatment. The announcement was made in London on July 13, at a meeting between AstraZeneca CEO Pascal Soriot and Australia’s Prime Minister Malcolm Turnbull. AstraZeneca will add three production lines to the existing eight at its Sydney site, each with a capacity to produce over 70 million units of Pulmicort respules in a year. The company will bolster exports from the site to over US$ 1.9 billion (AUD 2.4 billion) in the next four years, with a further goal of doubling respules production to 1 billion by 2025. “The demand for this asthma product, particularly for children in China, is immense and we see that trend continuing,” Mark Morgan, manufacturing director of AstraZeneca Australia, said. Although labor costs are lower in China, the manufacturing technology “is difficult to replicate,” Morgan added. Over 50 percent of Pulmicort’s worldwide sales come from China. And its demand increased by 18 percent — from US$ 485 million in 2015 to US$ 570 million in 2016. White House tells FDA to fund itself via industry fees; FDA scouts for top talent In the US last week, the House of Representatives passed the bill that reauthorizes US Food and Drug Administration (FDA) to levy user fees. Soon after that, the White House reiterated its earlier call to amend the agreements so that the FDA is entirely funded by the medical products industries. In a statement, the White House said: “The Administration urges the Congress to provide for 100 percent user fee funding within the reauthorized programs… In an era of renewed fiscal restraint, industries that benefit directly from FDA’s work should pay for it.” Last week’s statement said President Trump is “concerned with certain other provisions in the bill, such as those providing additional market exclusivity to manufacturers, which could make exclusivity unpredictable and decrease competition.” Meanwhile, the FDA Commissioner Scott Gottlieb is embarking on a talent hunt to recruit new staffers for the Prescription Drug User Fee Act (PDUFA)-related positions in the drugs and biologics programs. “To take on this new effort, we’re establishing a dedicated group of full-time staff with the responsibility to ensure that we reliably and predictably identify, recruit, and efficiently hire the scientific personnel the Agency needs,” Gottlieb said in his blog. Novartis’ CAR-T cell therapy unanimously recommended for approval by FDA The US FDA’s advisory committee has unanimously (10:0) recommended Novartis’ CAR-T cell therapy — CTL019 (tisagenlecleucel) — for approval to treat pediatric and young adult patients with B-cell acute lymphoblastic leukemia (ALL). CAR-T is short for chimeric antigen receptor T cell (CAR-T) therapy. In the US, ALL is the most common childhood cancer. This therapy is an immunotherapy approach to treat cancer, also considered the “fifth pillar” (after surgery, chemotherapy, radiation and targeted therapies like imatinib and trastuzumab) of cancer treatment. This approach, called adoptive cell transfer (ACT), uses engineered immune cells to generate remarkable responses in patients with advanced cancer. In several early stage trials, when ACT was tested in patients with advanced ALL (with few treatment options left before these patients), many reported a complete disappearance of the cancer. And these patients remained cancer free for extended periods. Therefore, Novartis’ CTL019 assumes tremendous importance. Meanwhile, the FDA advisory committee also unanimously recommended Biocon/Mylan’s and Amgen’s biosimilars for approval. The two recommendations imply a double whammy for Roche, with its drugs Avastin and Herceptin poised to get impacted by these biosimilars. The FDA’s Oncologic Drugs Advisory Committee (ODOC) voted 16-0 in favor of Milan’s proposed Herceptin biosimilar to treat HER2-positive breast cancer, both for patients after surgery and for metastatic disease. The ODOC also voted 17-0 to recommend FDA approval for Amgen’s ABP 215, an Avastin biosimilar, in each of the approved indications for the reference medication. The uses include metastatic colorectal cancer, non-squamous non-small cell lung cancer and glioblastoma. Concord Biotech faces GMP concerns; FDA warning letters to firms in India, Italy Ahmedabad-based Concord Biotech, a research and development-driven biotech firm that makes fermentation-based APIs, was placed on Health Canada’s Inspection Tracker due to “general GMP observations” shared by a regulatory partner. While no details of the observations were divulged, Health Canada did not mention any data integrity concerns and is “continuing to review evidence submitted (i.e. corrective actions, information from regulatory partner).” The FDA also issued a warning letter to Tubilux Pharma SpA in Italy over concerns arising from an inspection conducted in December 2016. The investigators raised concerns over turbulent airflow on an aseptic processing line which “poses a significant contamination hazard” to the product. Limitations in Tubilux’s “current equipment and process design” also posed “a significant hazard” in the aseptic processing operation. The warning letter also highlights that some of the products manufactured at Tubilux were not tested for particulates prior to release. During the inspection, FDA “observed repeated instances of high particle count alarms during production”. Tubilux specializes in manufacturing various types of products used in ophthalmic applications. A September 2016, FDA inspection at Vista Pharmaceuticals in India highlighted concerns over the sale of isoxsuprine hydrochloride USP, 20 mg tablets, by the firm. Although isoxsuprine hydrochloride is sold in the US, the drug is not approved in the Orange Book. The firm had also not validated the manufacturing process for isoxsuprine hydrochloride USP, 20 mg tablets. The warning letter also mentions that during the walk through of the firm’s manufacturing areas, FDA investigators observed that the equipment was in a state of disrepair. “Specifically, our investigators saw holes and corrosion in three pieces of equipment,” the letter noted. FDA chief pledges to accelerate generic reviews through two new policies This week, the US FDA Commissioner, Scott Gottlieb, made an announcement that by the end of 2017, the American drug regulator will issue two new documents to improve the review process for generic drugs. These documents are meant to streamline the submission and review of abbreviated new drug applications (ANDAs) under the FDA’s drug competition action plan. The first document is a planned internal manual of policies and procedures (MAPP) — titled “Good ANDA Assessment Practices”. It will look to reduce “unnecessary” and “duplicative” procedures from FDA’s reviews to make them more efficient. However, the document will not alter any of the review goals the FDA agreed to as part of the negotiations to reauthorize the GDUFA. For applications that aren’t approved, MAPP will instruct reviewers to detail what needs to be fixed in the complete response letter (CRL), and provide follow up with sponsors over phone if the reasons in the letter are unclear, Gottlieb said. The second document will be a guidance on “Good ANDA Submission Practices”. It will be added to the Center for Drug Evaluation and Research’s ‘to-do list’ for the year, which already includes 13 other new and revised draft guidances for generic drugs. According to Gottlieb, this guidance will detail common issues found in ANDA submissions and give sponsors advice on how to avoid those issues before submitting an application.

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20 Jul 2017