Generic drugs play a crucial role in providing access to life-saving drugs at affordable prices. To that end, drugmakers submit Drug Master Files (DMFs) or their ‘recipes for making generics’ to the US Food and Drug Administration (FDA) for review. Of these, Type II DMFs involve active pharmaceutical ingredients (APIs) for both branded and generic drugs.PharmaCompass has been reviewing Type II
submissions for several years now. We have noticed that these filings have been
increasing in recent years. There has been a 33.5 percent
increase in Type II DMF submissions since Q1 2018 (when 176 Type II DMFs had
been submitted). However, at 235, the first quarter (Q1) of 2024 saw only a 1.3
percent increase in DMF submissions over Q1 2023. In Q1 2023, DMF submissions
had increased by 21.5 percent (over Q1 2022).Of the 235 Type II submissions received by the FDA in Q1 of this
year, only 35 (or around 15 percent) had their review completed under the Generic Drug User Fee Act (GDUFA). The total number of reviews completed by the US federal agency so far this year is 129.In all, FDA received 353 Type II, III, IV, and V DMF submissions,
compared to 291 in Q1 2023, an increase of 21.3 percent.View FDA DMF Filings in Q1 2024 (Power BI Dashboard, Free Excel Available)DMF submissions from India
dip 1.8%; China witnesses 42% rise in filings As has been the trend, India (dubbed as the pharmacy of the world) and China filed the maximum DMF submissions, with 107 and 101 submissions respectively. However, DMFs filed by Indian companies saw a marginal dip of 1.8 percent in Q1 2024 — in Q1 2023, Indian companies had filed 109 Type II DMFs. Meanwhile, DMF filings by Chinese drugmakers increased 42.2 percent in Q1 2024, up from 71 in Q1 2023.India’s MSN Laboratories was the clear leader with 15 DMF submissions to the FDA, while China’s Sichuan Elixir
Pharmaceutical came a distant second with nine submissions. Indian drugmakers Aurobindo Pharma and Global Calcium (with seven submissions each) were tied at third position. There were two players at the fifth spot — India’s Dr. Reddy’s Laboratories and China’s Zhejiang Jingsheng
Pharmaceutical — as both these drugmakers registered six submissions each.View FDA DMF Filings in Q1 2024 (Power BI Dashboard, Free Excel Available) Diabetes, cancer drugs emerge
as hot molecules in Q1 2024Approved in June 2020, triheptanoin is the first and only FDA-approved treatment for
children and adults with long-chain fatty acid oxidation disorders (LC-FAOD).
At five, triheptanoin saw the maximum DMF filings.
Four of those applications have already been positively reviewed.Anti-diabetic drug sitagliptin phosphate
monohydrate saw four DMF filings. Empagliflozin, the API found in Boehringer Ingelheim and Eli Lilly’s diabetes drug Jardiance, drew three DMF filings in Q1 2024.In the US, Jazz Pharmaceuticals’ Zepzelca (lurbinectedin) is indicated for the treatment of adult patients with metastatic small cell lung cancer (SCLC). Three DMF applications were submitted for lurbinectedin. Similarly, ruxolitinib phosphate, used for the treatment of
patients with intermediate or high-risk myelofibrosis, also received three DMF
applications.Semaglutide — the glucagon-like peptide-1 receptor agonist that catapulted Novo Nordisk to the position of the most valuable public company in Europe — received three DMF filings. Semaglutide’s arch rival, tirzepatide, also drew three DMF filings.AstraZeneca’s Brilinta (ticagrelor) plus aspirin is currently approved in
over 115 countries for the prevention of stroke, heart attack, and other events
in adults with acute coronary syndrome (ACS). Ticagrelor received three DMF
submissions. Vonoprazan fumarate, a first-in-class potassium-competitive acid
blocker to treat acid-related diseases, also received three DMF submissions.View FDA DMF Filings in Q1 2024 (Power BI Dashboard, Free Excel Available) Eighteen DMFs filed for first
time in Q1 2024 During the first quarter of this year, 14 drugs saw first time filing of DMFs. Together, these 14 drugs attracted 18 DMF filings with tirzepatide topping the list with three submissions from Chinese companies.The 14 drugs that saw first time filing were clascoterone, capmatinib hydrochloride, niraparib tosylate
monohydrate, vibegron, cabozantinib sulfate,
ruxolitinib hemifumarate, ripretinib, ruxolitinib, ruxolitinib mesylate, tucatinib hemiethanolate, tecovirimat, tirzepatide, tolvaptan povidone, and azilsartan.View FDA DMF Filings in Q1 2024 (Power BI Dashboard, Free Excel Available) Our viewUntil 2020, DMF submissions by Indian companies used to be double those of Chinese and American
firms put together. In 2022, DMF filings from India began to dip, while
submissions by Chinese companies began to rise. In the first half of 2023,
there was a 46.5 percent rise in DMF submissions from China. The gap between
DMF filings by India and China has narrowed down considerably this year. The
reasons behind this phenomenon may be multiple. But it definitely implies that
America will find it increasingly difficult to reduce its reliance on China.
Impressions: 2442
The year
2021 was eclipsed by the Covid-19 pandemic. In our update for the first half of 2020, we had mentioned that
Covid-19 has not slowed down the speed at which generic active pharmaceutical
ingredient (API) manufacturers were submitting Drug Master Files (DMFs) to the
US Food and Drug Administration (FDA). That trend continued in 2021, when the
speed of DMF submissions to the agency remained similar to that witnessed in
the previous years.
In fact,
Type II DMFs, or DMFs for active pharmaceutical ingredients (APIs), were higher
in 2021 as compared to previous years. In the first quarter, FDA received 164
Type II DMF submissions, which rose to 165, 166 and 172 submissions over the
next three quarters. In all, 667 Type II DMFs were filed in 2021, as opposed to
662 in 2020, 633 in 2019 and 644 in 2018.
DMFs are
submissions made to the FDA by manufacturers who provide the agency with
confidential, detailed information about facilities, processes or articles used
in manufacturing, processing, packaging and storing of human drug
products.
Overall,
2021 saw a total of 913 DMFs (Type II, III, IV and V) being submitted. In
comparison, FDA had received 931 DMF submissions in 2020, 894 in 2019 and 979
in 2018.
View FDA DMF Filings in 2021 (Power BI Dashboard, Free Excel Available)
India
continues to lead DMF filings, followed by China
Country-wise
data on DMF filings at
the FDA tells us the potential of a country in the field of pharmaceuticals. At the company-level, with each DMF filing, a firm commits itself to manufacturing drugs in a facility that is aligned to the FDA’s rules and regulations.
This year
too, DMFs filed from India and China were significantly higher than those from
other countries. Expectedly, India continued to lead with 376 DMF filings.
Submissions from India were over twice that of DMF filings from China (at 159).
This is not surprising since the two countries have the maximum number of API
manufacturing facilities registered with the FDA.
As compared
to this, the United States had 52 DMF filings, Italy had 10, Spain and Taiwan
had 9 each, and countries like Canada, Israel, Japan and UK had five DMF
filings each.
View FDA DMF Filings in 2021 (Power BI Dashboard, Free Excel Available)
India’s MSN Labs leads DMF count
As in the
past, India's MSN Laboratories continued to lead the DMF filings by a single company with 43 submissions. MSN was followed by five other Indian companies — Dr. Reddy’s Laboratories filed 15 submissions, Hetero Group and Aurobindo Pharma 14, Metrochem API 13 and Aurore Life Sciences filed 12 DMF submissions.
The only
Chinese company in the top 10 by DMF count was Brightgene Bio-Medical Technology Limited with nine DMF submissions.
The maximum
number of DMF filings were for semaglutide (eight), followed by favipiravir (seven), apalutamide (six), sitagliptin phosphate (six) and tofacitinib citrate (six). Others like acalabrutinib, elagolix sodium, lenalidomide, liraglutide and pantoprazole sodium had five DMF filings each.
View FDA DMF Filings in 2021 (Power BI Dashboard, Free Excel Available)
Slow
assessment review, higher GDUFA fee
Although
there were 667 Type II DMFs filed with the FDA, only 194 (or 29 percent) had
their review completed. The GDUFA (short for Generic Drug User Fee Amendments)
fee associated with a DMF assessment review for 2021 was considerably higher — at US$ 69,921 — as opposed to US$ 57,795 for 2020. For FY 2022, the GDUFA fee has been revised upward to US$ 74,952 (an increase of US$ 5,031).
There are 42
products for which a DMF was filed for the first time. Among the patented
products which should expect generic competition are avatrombopag, encorafenib, esketamine hydrochloride, siponimod fumaric acid, tedizolid phosphate and vorapaxar sulfate.
In fact,
DMFs were also filed for products that are yet to receive an FDA approval. Some of these products are imeglimin, aviptadil, gimeracil, linzagolix choline, meglumine antimoniate, roluperidone hydrochloride and teneligliptin.
View FDA DMF Filings in 2021 (Power BI Dashboard, Free Excel Available)
Our view
The Covid-19
pandemic revealed how the global supply chain for pharmaceuticals is excessively dependent on India and China. As a
result, many countries across the world are making investments into expanding
their API production capacities. This should translate into more Type II DMF
filings from countries other than India and China.
Moreover, as the pandemic begins to wane and the FDA increases its inspections — both domestic and international — compliance issues are bound to increase. The US is planning to run a pilot program
soon that will test a system of unannounced inspections in India and China.
Companies in both India and China will need to increase their focus on
compliance if they wish to continue to be major contributors to the global
supply chain for pharmaceuticals. We can certainly expect more regulatory news
in 2022.View FDA DMF Filings in 2021 (Power BI Dashboard, Free Excel Available)
Impressions: 5639
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)
Impressions: 55103
At PharmaCompass, we highlighted
the significance of India in the global active pharmaceutical ingredient (API)
supply chain last week with our list of generic drug facilities registered with
the US Food and Drug Administration (FDA).
Our compilation revealed that India had
182 generic drug facilities registered with the FDA and this number was nearly
as much as the corresponding numbers for China (100) and United States (84) put
together. These 182 facilities paid a fee of US$ 59,400 each to the FDA.
View FDA DMF Filings in 2019 (Power BI Dashboard, Free Excel Available)
This week, we review the API Drug Master
Files (DMFs) submitted to the FDA in 2019. Expectedly, India also led the DMF submission list.
In 2019, there were 616 active DMF submissions
to the FDA with Indian companies submitting more than half (331) of them.
Submissions from India were a little less than double the number of DMF
submissions made by Chinese (113) and the US (57) firms put together.
Drug master files (DMFs)
are submissions made to the FDA by manufacturers by providing the agency with
confidential, detailed information about facilities, processes, or articles
used in manufacturing, processing,
packaging, and storing of human drug products.
View FDA DMF Filings in 2019 (Power BI Dashboard, Free Excel Available)
MSN Labs
leads total count of DMF filings
The 616 active DMF filings to the FDA were quite diverse — they covered over 400 products, and over half (322) the filings were for unique products.
Among the products with multiple DMF
filings, Sugammadex Sodium topped the list as it had 18 DMF
filings. Sugammadex is the API used in Merck’s Bridion for the
reversal of neuromuscular blockade induced by rocuronium and vecuronium in
general anesthesia.
The other products with over five DMF
filings were for the APIs of Lundbeck and Otsuka’s antipsychotic drug Brexpiprazole, Novartis, Gilead and Intercept’s blockbuster products Sacubitril-Valsartan, Tenofovir Alafenamide Fumarate and Obeticholic Acid.
View FDA DMF Filings in 2019 (Power BI Dashboard, Free Excel Available)
The year 2019 also witnessed continued
DMF filings for Rivaroxaban, Sitagliptin Phosphate, Ticagrelor and Tipiracil Hydrochloride. These filings indicate that the
companies currently developing these products should brace themselves for
intense competition in the near future.
India’s MSN Labs continued to lead the count of total DMF
filings with 42, of which it had 17 filings where it was the only one
submitting a DMF for a specific product in 2019. The leading Chinese company
filing DMFs was Fuxin Long Rui Pharmaceutical with nine DMFs, followed by Brightgene Bio-Medical Technology Co with five.
The API DMF is part of
the final generic drug product submission to the FDA. Therefore, the owner of a
DMF incurs a one-time fee (US$ 55,013 for FY2019, US$ 57, 795 for FY2020) the
first time the generic drug submission references that DMF.
View FDA DMF Filings in 2019 (Power BI Dashboard, Free Excel Available)
DMF holders may also pay
the fee in advance in order to have their DMF subjected to an initial
completeness assessment by the FDA. This would allow their DMF to be included
on a publicly-available list of DMFs that have paid their fee and not
failed the initial completeness assessment.
Aurobindo, Sun, Lupin lead DMF assessments
While reviewing the DMF submissions made in 2019, we found that a third (209 out of 621) of the DMFs were listed on FDA’s publicly-available list of DMFs that have paid their fee and whose initial assessment had been completed. This indicates that either companies may have been unwilling to pay the fee or the FDA’s review process found shortcomings in their applications.
Major Indian generic drug companies like Aurobindo (16), Sun Pharmaceuticals (13), MSN Labs (12), Lupin (7) and Macleods (7) led the list of companies that had
the maximum DMF assessments completed for their 2019 submissions.
There are also DMF submissions for
products which can sometimes indicate future drug approvals.
View FDA DMF Filings in 2019 (Power BI Dashboard, Free Excel Available)
Sanyo Chemicals submitted a DMF for Ibudilast, an anti-inflammatory drug whose oral
capsules are used in Japan for the treatment of asthma and its ophthalmic
solution is used to treat allergic conjunctivitis. The product is currently not
approved in the United States.
New drug approvals in the future can also
be expected for Tertomotide, Omarigliptin, Estetrol Monohydrate, Abametapir, Pirenzepine, Cortexolone Proprionate, Lurbinectedin, Terlipressin, Ethyl Olivetolate, Remimazolam and Triapine. These products are currently under
clinical trials for a variety of indications.
Our view
After compiling the list of companies that have submitted DMFs to the FDA as well as the generic facilities that paid their user fees, it’s clear that the API industry is beginning to find a new equilibrium.
View FDA DMF Filings in 2019 (Power BI Dashboard, Free Excel Available)
Our compilations of the previous years
have shown that there is a steady decline in facility registrations and DMF
filings. Given the increasing costs involved, as well as scaled up regulatory
requirements, it seems that companies are becoming more selective in their
product development decisions and also their willingness to do business in the
United States.
While the number of Indian API facilities
registered with the FDA has remained relatively unchanged, the number of
Chinese sites that registered with the US has reduced by 35 percent over the
past five years.
Several factors are changing the landscape of the generic drug industry. For instance, environmental regulations in China are driving up the cost of raw materials. Quality issues — such as the valsartan impurities case — have increased regulatory scrutiny. Moreover, passing inspections continues to remain a challenge for many manufacturers. And generic drug product manufacturers are also facing margin pressures, which in turn is driving a lot of M&A activity. Given this scenario, the generic industry should brace itself for more challenges in 2020.
View FDA DMF Filings in 2019 (Power BI Dashboard, Free Excel Available)
Impressions: 8296
This week, PharmaCompass reviews the recently released data of the Medicare Part D Prescription Drug Program in the United States for calendar year 2017.
The US market is the world’s largest and most important pharmaceutical market, accounting around 45 percent of the global share of drugs, and was valued at US$ 466 billion in 2017.
View Our Interactive Dashboard on Medicare Part D 2017 Spending (Free Excel Available)
What is Medicare?
Medicare is the federal health insurance program in the US which covered 58.4 million people in 2017 — 49.5 million aged 65 and older, and 8.9 million disabled.
The National Health Expenditure (NHE) in the US grew 3.9 percent to US$ 3.5 trillion in 2017 and accounted for 17.9 percent of the gross domestic product
(GDP). As a result, Medicare spending grew 4.2 percent to US$ 705.9 billion in
2017, or 20 percent of the total NHE.
Prescription
drug spending in the US increased to US$ 333.4 billion in 2017 while prescription drug coverage under the Medicare program,
known as Medicare Part D, reached US$ 151.6 billion in 2017, a little less than half of the total prescription
drug spending in the United States.
View Our Interactive Dashboard on Medicare Part D 2017 Spending (Free Excel Available)
Why has Medicare been in news?
The Medicare Part D drug benefit is delivered by private drug plans, which are mostly chosen by the program’s participants. Under Part D, drug prices are determined primarily through negotiations between Part D plans and providers (such as pharmacies and drug manufacturers). A key factor that helps Part D plans lower drug costs are rebate payments that the plans negotiate with drug manufacturers.
With drug pricing debate raging in the
United States, these rebate payments have come under a lot of scrutiny.
View Our Interactive Dashboard on Medicare Part D 2017 Spending (Free Excel Available)
During the hearing of Big Pharma executives summoned by the Senate
Financing Committee last month, Sanofi’s CEO Olivier Brandicourt detailed a chart showing Sanofi and Genzyme's US sales from 2018, explaining how as much as 55 percent of Sanofi’s gross sales were given back to payers as rebates.
The chart showed how out of Sanofi’s US$ 21.6 billion in gross sales in 2018, US$ 4.5 billion was given back in mandatory rebates to government payers and US$ 7.3 billion in discretionary rebates.
Earlier this month, the Trump administration
unveiled a budget that would reduce spending in Medicare as
well as Medicaid by hundreds of billions of dollars compared to the current
law.
View Our Interactive Dashboard on Medicare Part D 2017 Spending (Free Excel Available)
What are the insights available from the
2017 US Medicare Part D data?
The Medicare Drug Spending dashboards were updated earlier this month to include data for 2017, providing more
data and transparency to better identify trends and track consumption and price
changes over time.
Using the available data, PharmaCompass has developed its own dashboard to show
recent trends in consumption of prescription drugs under Medicare D. Our
dashboard also helps identify drugs with limited to no competition.
The data reveals that while almost 60 percent of the Medicare spend (nearly US$ 90 billion) is for drugs with only one manufacturer, i.e. mostly patented drugs, there is another US$ 12 billion spend on drugs which have only two manufacturers. The next highest spend — of US$ 4 billion — is on drugs with as many as five manufacturers.
This clearly indicates that if the market
can support up to five manufacturers for established products, increased
generic competition will significantly help Medicare reduce its Part D
prescription drug spending.
View Our Interactive Dashboard on Medicare Part D 2017 Spending (Free Excel Available)
Medicare’s highest spend was on Insulin Glargine (US$ 4.7 billion) followed by patented
drugs Celgene’s Revlimid (lenalidomide), Bristol-Myers Squibb’s Eliquis (apixaban), Merck’s Januvia (sitagliptin phosphate) and AbbVie’s Humira (adalimumab).
Drugs with limited to no competition can be
identified using the dashboard by sorting for drugs with few
manufacturers.
Information is also provided on drug uses
and clinical indications, thereby enabling comparison between different
medications for a given condition.
View Our Interactive Dashboard on Medicare Part D 2017 Spending (Free Excel Available)
Impressions: 4725
This week in Phispers, we look at how Mylan’s president Rajiv Malik and Emcure’s CEO Satish Mehta, along with 12 major generic drug players, got added to an expanded investigation into the drug price-fixing case in the US. While Trump declared the opioid crisis a health emergency, pharma companies Celgene and Gilead saw their third quarter results and guidance get impacted by a drug trial failure and competition. Meanwhile, there was news on Novartis buying AAA, CVS Health showing interest in buying health insurer Aetna and Merck cutting jobs and withdrawing its application for Keytruda as treatment for advanced lung cancer.
Mylan’s president, Emcure’s CEO, 12 firms to be probed in price-fixing case
This week, attorneys general from 45 US states named Mylan’s president Rajiv Malik and Emcure’s billionaire CEO Satish Mehta as they expanded their three-year old
investigation into price-fixing in the generic pharmaceuticals industry.
In addition to the two individuals, 12 major generic drug companies and 13 drugs were added to the expanded investigation. This week’s filing alleges collusion of 18 defendant companies, as well as two individual executives, involving a total of 15 drugs.
(To view the complete list of companies and
drugs, click here)
The states allege multiple conspiracies that restrained trade, artificially inflated and/or maintained prices and reduced competition in the generic drug industry. According to the expanded complaint, Mehta and Malik were “directly involved in conceiving an illegal agreement and taking affirmative steps to ensure it was executed by their subordinates.”
Earlier this year, a federal criminal investigation resulted
in the convictions of former Heritage Pharmaceuticals CEO Jeffrey Glazer and former Heritage President Jason
Malek. Heritage is a wholly-owned subsidiary of Emcure. Both Glazer and Malek pleaded guilty and have been cooperating in the anti-trust investigations being conducted by
federal and state prosecutors.
PharmaCompass had covered the illegal practices at
Heritage Pharmaceuticals that had come to light when Emcure had filed a lawsuit
against Glazer. It now remains to be seen if Glazer acted on his own or
colluded with his bosses in India to fix generic drug prices in the United
States.
As Trump declares opioid crisis an emergency, Insys founder
gets arrested
Last week, the US President Donald Trump hardened his stand on the
opioid crisis, blaming it on factors like criminals, drug companies, Mexico and
China. In the US, the crisis claimed over 30,000 lives in 2015.
He termed abuse of opioids a public health emergency and outlined steps to fight it — such as new efforts to curb prescription abuse, reduction in import of certain drugs and educating children on the risks.
“We must stop the flow of all types of illegal drugs into our communities,” Trump said. Blaming pharmaceutical companies for over-prescribing pain medications, he said the US Food and Drug Administration (FDA) will provide more training to doctors who prescribe drugs to prevent abuse. Moreover, he has requested that one opioid drug, Opana ER, no longer be sold.
According to Trump, a border wall with Mexico will “greatly help” reduce this problem. He also talked about China’s role in the production of fentanyl.
Meanwhile, John Kapoor, the founder of Insys Therapeutics, was arrested last week on
charges of participating in a scheme to bribe doctors to prescribe a
fentanyl-based cancer pain drug. Kapoor has resigned from the company’s board of directors, and his arrest is being seen as a step towards fighting the opioid epidemic.
The charges against Kapoor marked a major
escalation of probes into Subsys, an under-the-tongue spray that contains
fentanyl, an addictive synthetic opioid.
Celgene’s Crohn’s disease drug fails trial; Gilead reports weak Hep C sales
Two companies have not had a good going — Celgene and Gilead. The former announced that its drug mongersen — a potential treatment for Crohn’s disease — had failed. Celgene had purchased the drug four years ago for US$ 710 million from a private company in Dublin — Nogra Pharma Limited. The New Jersey-headquartered biotech firm had promised that
if mongersen gets approved, Nogra would get another US$ 815 million. But that
was not to be.
What was worse, Celgene’s third-quarter financial announced last week spooked its investors. The
company missed analysts’ sales projections for the third quarter by 4 percent, cut its guidance for 2020 by 5 to 10 percent, and announced that sales of a key (plaque psoriasis) drug — Otezla — had missed forecasts by US$ 100 million.
In a note, Geoffrey Porges, a biotech analyst at Leerink, said: “Investors are likely to ask whether the company’s good fortune has run out, with disappointments (mongersen) and negative revisions (Otezla) left and right.”
Gilead, on the other hand, is trying hard to move away from hepatitis C. Its hepatitis C drugs generated US$ 2 billion during the last quarter — just US$ 300 million short of Wall Street’s projections. However,
investors were cautioned about AbbVie’s new launch —Mavyret — which is expected to have a “big impact” on Gilead’s fourth-quarter results.
Gilead’s hepatitis C drugs have been facing competition from new rivals who have eaten into its market share and driven down prices over the last few quarters.
However, we could expect some M&A action soon. “Gilead noted that it is in a ‘constant state of valuation and opportunities’ and that it is very, very active,” said an analyst.
Novartis buys radiopharmaceutical firm AAA for
US$ 3.9 billion
In July, PharmaCompass had covered news on how Lutathera — a nuclear medicine targeted at the type of cancer that killed former Apple Inc co-founder and CEO Steve Jobs — got a nod from the European Medicines Agency (EMA), boosting prospects for its developer Advanced Accelerator Applications (AAA).
Well, last week the French biotech — AAA — got bought over by Novartis for
US$ 3.9 billion. Novartis is paying a 44 percent premium over AAA’s market valuation from September 28.
The deal further strengthens Novartis’ oncology business, which had got a shot in the arm in 2015, when it
acquired GlaxoSmithKline’s marketed cancer drugs. And in August, its gene-modifying leukemia treatment (a chimeric antigen receptor T-cell therapy or CAR-T therapy) — Kymriah — got approved. This was the first CAR-T therapy to bag an FDA approval.
With AAA, Novartis will now have a
technology that deploys trace amounts of radioactive compounds to not only
diagnose a disease (by creating images of organs and lesions), but also to
fight cancer.
Lutathera is a radiopharmaceutical — it uses radioisotopes to target neuroendocrine tumors. Along with Lutathera, Novartis also gets a pipeline of drugs from AAA with some near-term potential.
US Merck to cut 1,800 jobs, withdraws EU
application of cancer wonder drug
Late last week, Merck announced it had withdrawn its application for
Keytruda (pembrolizumab) as a combination treatment for an advanced stage of
non-small cell lung cancer (NSCLC) from the European Medicines Agency
(EMA).
An analyst with Evercore ISI, Umer Raffat, said
in a note that EMA was reluctant to approve drugs based on Phase II data, even
though the FDA regularly does so in oncology.
The company is also moving to a new sales team structure in the
US, and plans to cut 1,800 sales positions, while adding 960 jobs to a new
chronic care salesforce.
According to a Fox Business report, three of Merck’s US sales teams will be cut: primary care, disease-focused endocrinology and hospital chronic care. This is “to better support changes in our business in the United States,” Merck’s spokeswoman said.
Merck’s new chronic care team will focus on Januvia (a diabetes drug), other primary care products such as sleep medication Belsomra, and products for respiratory conditions and women's health, she added.
Releasing its third quarter numbers in the
US, Merck was also forced to concede that the NotPetya cyber attack had cost the company US$ 135 million in lost sales
along with US$ 175 million in related costs. That extra US$ 310 million in
costs will be repeated in Q4 as overall damages inch up to the US$ 1 billion
mark, the company said.
As Amazon threat looms over US pharmacy
biz, CVS eyes health insurer Aetna
Amazon has been trying to get into the US$ 412 billion pharmacy
business in the US. Every year, pharmacies in the US dispense about 4.5 billion prescriptions. Patients pick up about 9 out of 10 prescriptions at a retail pharmacy. Amazon’s entry into online
prescription drug sales, therefore, poses an existential threat to brick-and-mortar
pharmacies.
And that’s the reason why news about US pharmacy operator CVS Health Corp reportedly evincing interest in buying health insurer Aetna Inc is important. This potential acquisition could trigger another round of deal making in an industry that is fearing Amazon’s arrival.
According to news reports, CVS Health is expected to buy Aetna for US$ 66 billion
in what would be the biggest deal of the year.
If the deal goes through, it would also be
the biggest of its kind ever in healthcare. “A potential combination would diversify CVS profit streams ahead of an Amazon entry and set the stage for a new healthcare-retail delivery model,” Morgan Stanley analysts wrote
in a note.
A deal would make CVS-Aetna a one-stop shop for customers’ healthcare needs — which could range from employer healthcare and government plans to managing benefits and running drug stores.
Impressions: 3170
This week in Phispers, we analyze the
situation at AstraZeneca, where its much anticipated lung cancer drug failed in
clinical trials. In the US, there are reports that various generic players are
looking to enter into M&A deals in order to safeguard themselves against
regulatory crackdown on prices. The tension along the India-China border may
lead to cancellation of the Fosun-Gland deal by the Indian government and in
the US, the FDA is looking to cut nicotine in cigarettes to ensure they are
non-addictive.
AstraZeneca’s key lung cancer drug fails in first stage trial; gets investors worried
The year 2017 was supposed to be a pivotal year for AstraZeneca.
The firm was supposed to display new marvels from its laboratories and march
towards annual revenues of US$ 45 billion by 2023. This target was set when Pfizer’s
takeover offer was rejected in 2014.
But so far, the year has turned out horribly for AstraZeneca. Its key lung cancer drug — Imfinzi — flopped in clinical trials.
Known as the ‘Mystic’ study, this was the most anticipated clinical experiment in the pharmaceutical industry this year. The study was key to proving the value of the group’s new drug pipeline, after it rejected a US$ 118 billion takeover bid by Pfizer in
2014.The news crashed the share price of
AstraZeneca by 15 percent.
Imfinzi, an immuno-oncology drug, was said to be a potential replacement for chemotherapy. However, all is not lost yet. The first stage of the trial merely measured the drug’s ability to prevent a cancer from becoming worse. The second stage, which looks at survival rates, is said to be more important.
But for Pascal Soriot, AstraZeneca’s CEO, this came as an embarrassment. He faced a barrage of questions from analysts about future payouts of the company. He was forced to defend the company’s dividend strategies at post-result meets last week. Fears for AstraZeneca’s dividend were driven by the failure of the lung cancer.
But there is hope for Astra in the future — another lung cancer pill, Tagrisso,
has produced good data. And AstraZeneca is partnering with Merck on another
immuno-oncology drug, Lynparza.
Another downside for Astra in 2017 has
been the uncertainties faced by the company regarding its top executives. It
began in January this year, when Luke Miels, the head of AstraZeneca’s European operations, announced he is quitting the company to join GlaxoSmithKline. Recently, there were speculations regarding Soriot
considering an offer to join Israeli drugmaker Teva as its head.
He is learnt to have turned down the offer.
Bleak US generics market forecast has
drug makers scrambling for deals
In the US, generic drug makers are turning to M&As in order to safeguard themselves against a concerted
effort by regulators to crack down on the steep prices of drugs.
According to a Reuters report, Impax Laboratories,
Perrigo and Alvogen have been
talking to advisers about various strategic options for their generics
businesses. These options range from acquisitions,
as well as outright sale.
Earlier, Reuters had reported
that Mallinckrodt,
one of the largest producers of the generic opioid painkiller oxycodone, has been exploring a sale of its specialty generics unit. In May, the CEO of Impax, which makes a generic version of the EpiPen allergy injection, said it was looking at deals.
The US generics market is getting
increasingly competitive. Last month, Novartis reported that sales at its Sandoz generics
unit were down 4 percent.
Generic drugs are cheaper versions of brand-name drugs. In the US, the
government is targeting generics to cut the cost of prescription drugs.
According to a 2016 report by the Journal of the American Medical Association,
US consumers spend more than twice as much on drugs per capita compared to
other industrialized nations.
In order to bring down the prices of
drugs, the US Food and Drug Administration (US FDA) has committed to
eliminating the backlog of drug applications awaiting its approval. This could
mean nearly 4,000 new drugs will come onto the market over the next few years,
based on FDA estimates.
Even today, small and mid-sized drug
makers are under pressure as consolidation among generic drug distributors has
made it less profitable for them to sell their drugs.
India-China border skirmish may impact Fosun-Gland deal
The heightened tensions along the
India-China border are likely to impact business. In the pharmaceutical
industry, the Cabinet Committee on Economic Affairs (CCEA) in India is likely to reject Shanghai Fosun Pharmaceutical Group’s US$
1.3 billion acquisition of Hyderabad-based Gland Pharma Ltd, says a Bloomberg
report.
However, a report in The Economic
Times says the proposal was listed for CCEA’s consideration two weeks back. But the CCEA is yet to take a call on the Gland Pharma-Fosun
deal.
“It is wrong to say that the deal has been rejected,” the official said. The Gland Pharma-Fosun deal had been approved by the now-abolished Foreign Investment Promotion Board (FIPB) in March this year. And Fosun was to acquire 86 per cent stake in the injectable drugmaker.
According to IndiaSpend, China is today the 17th largest foreign direct investor in India, an
improvement on the 36th rank it held in 2010.
CRO Consolidation: LabCorp buys
Chiltern, Evotec acquires Aptuit
Consolidation in the CRO industry
continued unabated last week. LabCorp bought Chiltern for US$ 1.2 billion last week. Two years back, LabCorp had bought Covance for US$ 6.1
billion. The acquisition of Chiltern will add another 4,500 clinical
outsourcing workers around the globe to its employee roster.
Another CRO that made an acquisition last week was Germany’s Evotec. It bought out its rival Aptuit for US$ 300 million in cash. And the
deal will add hundreds of scientists to its organization along with facilities
in Basel, Oxford and Verona.
Evotec has earned a large number of
clients on both sides of the Atlantic. Evotec says most of Aptuit’s
750 employees are scientists. Last year, Aptuit reportedly handled 1,000
projects for some 400 companies.
The CRO business has been
consolidating for years, with private equity groups leading the way to build up
these global organizations. Leading the pack is Thermo Fisher,
which had made acquisitions worth US$ 22 billion in the last five years. Three months back, Thermo Fisher Scientific acquired Patheon NV for US$ 5.2 billion while INC Research Holdings merged with private-equity owned CRO — inVentiv Health.
FDA to cut nicotine in cigarettes to non-addictive levels
Last week, the US government proposed cutting nicotine in cigarettes to “non-addictive” levels in order to move smokers towards potentially less harmful e-cigarettes. The FDA Commissioner Scott Gottlieb said the agency will study regulating nicotine levels with a view towards the “FDA’s potential to render cigarettes minimally addictive or non-addictive.”
“Nicotine itself is not responsible for the cancer, the lung disease and heart disease that kill hundreds of thousands of Americans each year,” Gottlieb said. “It's the other chemical compounds in tobacco and in the smoke created by setting tobacco on fire that directly cause illness and death,” he added.
The FDA cannot reduce nicotine levels
to zero, nor can it ban cigarettes. However, after this announcement by
Gottlieb, shares of major tobacco firms in the US and UK slumped.
Analysts said they expect regulators
in Europe to study similar actions on nicotine products. This action shakes up
a public health debate on whether e-cigarettes represent a health risk or a
potential benefit.
NotPetya cyber attack hits Merck’s profits
Merck is the latest in a string of
companies that have disclosed that their operations were significantly
disrupted by the NotPetya attack, which devastated businesses and government
agencies in Ukraine in June and has gradually spread around the globe.
According to a Reuters report, Merck said it had been a victim of an international cyber
attack in June 2017, due to which the company had to halt production of drugs.
As a result, its profits for the rest of the year have been hit.
The company, however, said it is yet
to know the magnitude of the impact as it is in the process of restoring
manufacturing operations.
Merck had disclosed the attack last month, but did not disclose the manufacturing shutdown at the time. The company said it was confident that it will be able to maintain a continuous supply of its top-selling and life-saving drugs, such as cancer drug Keytruda, diabetes drug Januvia and hepatitis C drug Zepatier.
However, there maybe temporary delays in delivering some other products, which
the company did not identify.
“Full recovery from the cyber-attack will take some time, but we are making steady progress,” CEO Ken Frazier said. At least four other major US and European firms have also experienced massive outages due to NotPetya.
Impressions: 2706
This week, Phispers tells us why David Hung’s taking charge as CEO of Axovant could signal the revival of an Alzheimer’s compound shelved by GSK. While, the FDA has extended compliance date for submitting DMFs in electronic format, there are also indications that there will be more FDA inspections in India. Plus, there is news on companies like Fresenius, Stada, Ajanta Pharma, Merck and Teva. Read on.
FDA
extends compliance date for electronic DMF submissions to May, 2018
On April
7, the US Food and Drug Administration (FDA) announced it is extending the compliance date for submitting DMFs in Electronic Common Technical Document (eCTD)
format to May 5, 2018.
“DMF submissions that are not submitted in eCTD format after this date will be rejected,” the FDA website said.
“Presentations on submitting in eCTD format created prior to April 7, 2017 will have the incorrect compliance date for DMFs,” it added. Electronic submissions of Drug Master Files (DMFs) were supposed to become mandatory from May 5, 2017.
The
news coincides with the US Senate’s confirmation hearing for Scott Gottlieb, on April 7. Gottlieb was President Trump’s nominee to be the next Commissioner of the FDA.
Gottlieb was with the FDA when the regulator launched its Pharmaceutical cGMPs for the 21st Century initiative. Out of five guidance documents
listed as part of this initiative, only one has been finalized.
With
Gottlieb heading back, Ajaz Hussain, (former FDA deputy office director and
president of the National Institute for Pharmaceutical Technology and
Education of NIPTE), Vadim Gurvich (executive
director of NIPTE) and Peter J. Pitts (president of the Center for Medicine in
the Public Interest and a former FDA associate commissioner) shared their
perspective on how Trump and the FDA can create a pharmaceutical manufacturing renaissance in a blog posted on Morning Consult.
Axovant appoints new CEO and revives ghosts of GSK’s billion dollar mistake
After
selling Medivation to Pfizer for US $ 14 billion and
exiting with US $ 354 million for himself, David Hung is now the CEO of Axovant, the company which we wrote about two years ago, as we asked the question — Did a 29-year old show GSK that it made a billion dollar mistake?
Back in December 2014,Vivek Ramaswamy, CEO and Founder of Roivant Neurosciences and Axovant, had bought an old Alzheimer’s drug that GSK had dropped for US $ 5 million. In October 2014, Roivant had spun off a subsidiary by the name of Axovant, which then bought the GSK drug. GSK had shelved the compound — 5HT6 — after testing it in 13 trials and on 1,250 patients.
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.
Throughout, Ramaswamy has recruited high-profile executives to run his companies. And who could be more high profile than Hung? The stock market cheered his appointment — Axovant’s stock was up 28 percent
earlier this week after Hung was announced its CEO.
Axovant is looking for positive data that GSK had gathered for its 5HT6 Alzheimer’s drug. And a number of senior players in the industry say Axovant has a decent shot at taking the successful dose back into the clinic. With Hung joining, it seems the drug discarded by GSK does indeed have merit.
Fresenius
in talks to buy Akorn; Stada sold for US $5.6 billion
Fresenius SE said
it is in talks to buy US generic drugmaker - Akorn Inc.
Though discussions are underway, there is no certainty of a deal, Fresenius
said. A spokeswoman for Akorn
declined to comment.
The CEO of Fresenius, Stephan Sturm, who took charge in July 2016, has been expanding the group’s global reach through acquisitions. Last year, the company bought Spanish hospital group IDC Salud Holding SLU, also known as Quironsalud, for US $ 6.11 billion (Euro 5.76 billion) in the company’s largest-ever acquisition.
Akorn could complement Fresenius’ Kabi medicines division, which specializes in intravenous drugs, and accounts for about a fifth of the company’s revenue.
Stada sell-off: Stada Arzneimittel AG has been sold to Bain Capital and Cinven for US
$ 5.6 billion (Euros 5.3 billion), after
a long-fought takeover contest. The sell-off will give the equity firms
control of one of the last independent generic-drug businesses in Europe.
The
deal would give buyers access to German and Russian markets for OTC and copycat
medicines. It marks another step in the consolidation of the generics
industry.
FDA inspections in India to rise, says Edelweiss Securities
India’s pharmaceutical sector is the largest supplier of drugs to the US. However, “quality issues are an ongoing challenge for the Indian pharmaceutical industry,” Mary Lou Valdez, FDA’s associate commissioner for international programs wrote in a blog.
Of the 42 warning letters sent out by FDA’s office of manufacturing quality last year, about one-fifth (9) were addressed to Indian facilities. The number could rise over the next three years as the FDA would inspect 190 facilities that it could not inspect in the past five years, wrote Edelweiss Securities.
FDA inspections in India and China have doubled since 2012.
This has led to a spurt in warning letters as well.
GSK to withdraw 600,000 inhalers; no observations for Ajanta
GSK would be voluntarily recalling close to 600,000 Ventolin asthma
inhalers across the US, says the FDA. The recall is due to a leak observed in
some of the products.
The exact number of inhalers to be recalled, as reported by the FDA, is 593,088. These were produced in GSK’s Zebulon, North Carolina manufacturing facility. This is the second time in just over a year that the plant has faced problems with leaking inhalers.
Ajanta Pharma: On Monday this week,
shares of India-based Ajanta Pharma soared by over
5 percent in intraday trading as investors cheered the fact that no observations were issued during a regulatory
inspection at its unit.
“Our formulation facility at Dahej (in Gujarat) was inspected by US Food and Drug Administration (FDA) from April 3 to April 7, 2017. At the end of the inspection, no Form 483 was issued to us,” Ajanta Pharma said in a notification to the stock exchanges.
FDA delivers a blow to Merck’s Januvia marketing plan
In 2015, Merck had come out with a massive 14,724-patient study where the data demonstrated that Type 2 diabetes patients could take its flagship DPP-4 drug — Januvia — without increasing their risk for cardio complications. DPP-4 inhibitors work by blocking the action of DPP-4, an enzyme which destroys the hormone incretin.
Merck wanted to use the
findings of this survey in a label to help distinguish themselves from
same-class rivals like Onglyza, which has risks.
However, the FDA recently nixed the idea, handing the pharma giant a complete response letter
(CRL).
The CRL covered Merck’s blockbuster Januvia as well as its combos with metformin. However, Merck says it
is reviewing the letter and will discuss next steps with the FDA.
Teva’s US $ 3.5 billion buy pays off with FDA approval of Austedo
Last week, the FDA gave its nod for Teva’s promising drug deutetrabenazine, after
putting it on hold ten months back due to certain suspicions regarding some
metabolites found in patients.
Teva had paid US $ 3.5
billion to acquire Auspex two years back. Teva’s deutetrabenazine is the
first deuterated drug to bag
an FDA approval.
A
deuterated drug is a drug where hydrogen has
been replaced by deuterium. A simple swap of six hydrogens with deuterium in an existing drug, Xenazine® (tetrabenzaine), resulted in an improved version of the drug, called deutetrabenzaine
or SD-809 (which had been developed by Auspex).
The
drug will be sold as Austedo. Due to the presence of deuterium, the drug breaks down more slowly in patients. This way physicians can give the drug less
often and at lower doses and still manage great results. The drug is designed
to regulate the levels of dopamine in
the brain.
Impressions: 3092
In less than three weeks, Donald Trump will assume office as the
President of the United States. He has mentioned that he wants Medicare (a
national social insurance program) to directly negotiate the price it pays for prescription drugs.
Medicare provides health insurance to Americans aged 65 or more, who
have worked and paid into the system through the payroll tax. It also provides
health insurance to younger people with some disabilities or end-stage renal
disease and amyotrophic lateral sclerosis.
In 2015, Medicare provided health insurance to over 55 million Americans — including 46 million people aged 65 or more, and nine million younger people.
As we flag off the New Year, PharmaCompass
provides insights into drug prices and prescription patterns in the US in order
to help professionals make informed decisions. We believe that the cost of
medicines in the US, which have been a subject of much public outcry and
discussions in the recent years, will continue to be scrutinized during 2017.
Medicare data for 2014
Medicare Part D, also known as the Medicare prescription drug benefit — the program which subsidizes the costs of prescription drugs and prescription drug insurance premiums for Medicare beneficiaries — published a data set (for calendar year 2014) which contains information from over one million healthcare providers
who collectively prescribed approximately US $121 billion worth of prescription
drugs paid for under this program.
For each prescriber and drug, the dataset
includes the total number of prescriptions that were dispensed (including
original prescriptions and any refills), and the total drug cost.
The total drug cost includes the ingredient cost of the medication, dispensing fees, sales tax, and any applicable administration fees. It’s based on the amounts paid by the Part D plan, the Medicare beneficiary, other government subsidies, and any other third-party payers (such as employers and liability insurers).
The total drug cost does not reflect any manufacturer rebates paid to Part D plan sponsors through direct and indirect remuneration or point-of sale rebates. In order to protect the beneficiary’s privacy, the Centers for Medicare & Medicaid Services (CMS) did not
include information in cases where 10 or fewer prescriptions were dispensed.
Top
Ten Drugs by Cost, 2014 [Most expensive for Medicare]
Drug Name
Total Claim Count
Beneficiary Count
Prescriber Count
Total Drug Cost
Sofosbuvir
109,543
33,028
7,323
$3,106,589,192
Esomeprazole Magnesium
7,537,736
1,405,570
286,927
$2,660,052,054
Rosuvastatin Calcium
9,072,799
1,752,423
266,499
$2,543,475,142
Aripiprazole
2,963,457
405,048
130,933
$2,526,731,476
Fluticasone/Salmeterol
6,093,354
1,420,515
281,775
$2,276,060,161
Tiotropium Bromide
5,852,258
1,211,919
253,277
$2,158,219,163
Lantus
Solostar
(Insulin Glargine)
4,441,782
972,882
224,710
$2,016,728,436
Sitagliptin Phosphate
4,495,964
789,828
190,741
$1,775,094,282
Lantus
(Insulin Glargine)
4,284,173
787,077
223,502
$1,725,391,907
Lenalidomide
178,373
27,142
9,337
$1,671,610,362
View the Medicare Part D National Prescriber Summary Report, Calendar Year 2014 (Excel version available) for FREE!
Top
Ten Drugs by Average Cost per Claim, 2014 [Most expensive drugs]
Drug Name
Total Claim Count
Beneficiary Count
Prescriber Count
Total Drug Cost
Average Cost Per Claim
Adagen
13
$1,224,835
$94,218
Elaprase
100
$6,560,225
$65,602
Cinryze
1,820
194
196
$96,155,785
$52,833
Carbaglu
60
$2,901,115
$48,352
Naglazyme
129
$6,189,045
$47,977
Berinert
538
73
68
$25,685,311
$47,742
Firazyr
1,568
269
232
$70,948,143
$45,248
H.P. Acthar
9,611
2,932
1,621
$391,189,653
$40,702
Procysbi
314
41
47
$12,542,911
$39,946
Folotyn
15
$598,210
$39,881
Top
Ten Drugs by Claims, 2014 [Most Commonly Used by Patients]
Generic Name
Total Claim Count
Beneficiary Count
Prescriber Count
Total Drug Cost
Lisinopril
38,278,860
7,454,940
464,747
$281,614,340
Levothyroxine Sodium
37,711,869
6,245,507
416,518
$631,855,415
Amlodipine Besylate
36,344,166
6,750,062
451,350
$303,779,661
Simvastatin
34,092,548
6,768,159
387,651
$346,677,118
Hydrocodone-Acetaminophen
33,446,696
8,005,790
677,865
$676,296,988
Omeprazole
33,032,770
6,707,964
475,122
$529,050,385
Atorvastatin Calcium
32,603,055
6,740,061
419,327
$747,635,818
Furosemide
27,133,430
5,176,582
456,047
$135,710,772
Metformin HCl
23,475,787
4,509,978
364,273
$203,948,989
Gabapentin
22,143,641
4,298,609
486,754
$492,557,255
View the Medicare Part D National Prescriber Summary Report, Calendar Year 2014 (Excel version available) for FREE!
Top
Ten Drugs by Prescribers, 2014 [Most Popular with Doctors]
Generic Name
Total Claim Count
Beneficiary Count
Prescriber Count
Total Drug Cost
Hydrocodone/Acetaminophen
33,446,696
8,005,790
677,865
$676,296,988
Ciprofloxacin HCl
7,253,018
4,926,835
568,201
$46,728,353
Amoxicillin
6,298,980
4,384,899
557,614
$31,193,739
Cephalexin
5,040,219
3,529,303
557,048
$36,987,401
Azithromycin
7,339,954
5,274,010
544,625
$70,699,119
Prednisone
11,032,986
4,505,821
536,108
$86,537,932
Tramadol HCl
14,250,227
4,272,724
515,816
$125,343,514
Sulfamethoxazole /Trimethoprim
4,833,758
3,090,944
500,790
$29,231,511
Gabapentin
22,143,641
4,298,609
486,754
$492,557,255
Amoxicillin/Potassium Clav
3,551,452
2,710,244
478,361
$61,713,432
The findings from CMS
data
The CY 2014 data represented a 17 percent
increase compared to the 2013 data set and a substantial part of the total estimated prescription drug spending (as estimated by the Department of Health and Human Services Office of the Assistant Secretary for Planning and Evaluation, or ASPE) in the United States — at about US $ 457 billion in 2015, which was 16.7 percent of the overall personal healthcare services.
Of that US $ 457 billion, US $ 328 billion (71.9 percent) was for retail
drugs and US $ 128 billion (28.1 percent) was for non-retail drugs.
The drug pricing process in the US is complex and
reflects the influence of numerous factors, including manufacturer list prices,
confidential negotiated discounts and rebates, insurance plan benefit designs,
and patient choices.
An IMS study found that across 12 therapy classes widely used in Medicare Part D,
medicine costs to plans and patients in Medicare Part D are 35 percent below
list prices.
View the Medicare Part D National Prescriber Summary Report, Calendar Year 2014 (Excel version available) for FREE!
While the CMS does not
currently have an established formulary, Part D drug coverage excludes drugs
not approved by the US Food and Drug Administration, those prescribed for off-label
use, drugs not available by prescription for
purchase in the US, and drugs for which payments would be available under Parts
A or B of Medicare.
Part D coverage
excludes drugs or classes of drugs excluded from Medicaid coverage,
such as:
Drugs used for anorexia, weight loss, or weight gain
Drugs used to promote fertility
Drugs used for erectile dysfunction
Drugs used for cosmetic purposes (hair growth, etc.)
Drugs used for the symptomatic relief of cough and colds
Prescription vitamins and mineral products, except prenatal vitamins and fluoride preparations
Drugs where the manufacturer requires (as a condition of sale) any associated tests or monitoring services to be purchased exclusively from that manufacturer or its designee
Our view
The Medicare program is designed such that the
federal government is not permitted to negotiate prices of drugs with the drug
companies, as federal agencies do under other programs.
For instance, the Department of Veterans Affairs — which is allowed to negotiate drug prices and establish a formulary — has been estimated to pay (on an average) between 40 to 58 percent less for drugs, as opposed to Medicare Part D.
If Trump administration kick starts direct
negotiations on Medicare drug prices with drug companies, 2017 will surely turn
out to be a year for the pharmaceutical industry to remember.
View the Medicare Part D National Prescriber Summary Report, Calendar Year 2014 (Excel version available) for FREE!
Impressions: 7966
This week, the
biggest news in the world of pharmaceuticals was the termination of the Pfizer-Allergan mega-merger due to new measures taken by the US government. Post that, Allergan signed a US $ 3 billion licensing deal with UK’s Heptares for a portfolio of neurological drugs. But a lot more happened last week – for instance, Pfizer and Celltrion won approval for a biosimilar of J&J’s Remicade, GSK said it wants to make it easier for manufacturers in least-developed
countries to make its drugs and Valeant terminated the salesforce for its female libido pill. Pharmaceutical
Whispers (Phispers) brings you the latest news from across the world. Pfizer-Allergan terminate
merger; Allergan signs licensing deal with HeptaresOn Monday, the US Treasury announced new measures to curb tax-inversion deals. The measures seemed to specifically target the Pfizer-Allergan US $ 160 billion mega deal. And, by Wednesday, the US government had achieved its desired objective – Pfizer and Allergan announced their decision to mutually terminate
the deal. Allergan, which is run from New Jersey but has a legal
domicile in Dublin, last year agreed to merge with Pfizer. This mega-merger
would have moved the Pfizer headquarters from New York to Dublin, saving the
pharma behemoth billions of dollars in taxes. As per news reports, Pfizer will need to pay a US $ 400
million fee to Allergan for expenses relating to the deal. Though the US
Treasury decision and the termination of the Pfizer-Allergan deal represents a
victory for President Barack Obama, whose administration proposed tougher rules
aimed at curbing tax inversions, Allergan is not wasting time. Just hours after Allergan backed away from the US $ 160
billion-merger with Pfizer, the company bounced back with a US $ 3.3 billion licensing deal for global
rights to a portfolio of drugs for neurological disorders from the UK's
Heptares. The deal sends a clear signal that Allergan CEO Brent Saunders plans
to barrel ahead with new pacts to bolster the company's pipeline. Pfizer, Celltrion win approval for biosimilar of J&J’s RemicadeNot all news this week was negative for Pfizer as the FDA approved Celltrion’s biosimilar application of Johnson & Johnson’s Remicade.
The product will be co-marketed by Pfizer in the United States, a relationship
Pfizer accessed through its acquisition of Hospira last
year. Celltrion’s application is only the second biosimilar approved by the FDA. However, unlike generic medicines, biosimilars which have been currently approved are not interchangeable with the reference drug. The European Medicines Agency also issued
a positive opinion to the Bioepis copy of Remicade. Samsung Bioepis, a joint
venture between a unit of the Samsung group and Biogen, has
become a force in the biosimilar drugs industry. In fact, South Korea too is
emerging as a hub for biosimilar production. Last week, Bioepis filed a lawsuit
against AbbVie Inc., makers of the world’s best-selling rheumatoid arthritis drug – Humira – which generated sales of US $ 14 billion last year. In 2015, Johnson & Johnson’s Remicade sales
were US $ 6.5 billion. Glaxo not to patent drugs
in poorer countriesIn an unusual step, GlaxoSmithKline said it wants to make it
easier for manufacturers in the world's 48
least-developed countries to copy its medicines. The company said it would not
file patents in these countries in the hope that by removing the fear of
patent litigation and by allowing independent companies to make and sell
versions of its drugs in those areas, it would widen
public access to these drugs. In countries classified as lower middle income countries by GSK, it will continue to file patents, but will grant licenses to generic manufacturers in exchange for a “small royalty”. Gilead
has adopted a similar model, of granting
generic licensing agreements in developing countries, for
its blockbuster Hepatitis C treatment, Sovaldi. The end of the female
Viagra?Valeant Pharmaceutical, still reeling from all its
accounting and price-gouging problems, has terminated
the sales force for the female libido pill that it acquired last year for US
$ 1 billion. The drug – Addyi (flibanserin) – failed to gain traction in its first six months on the market. Valeant’s stock has plunged 90 percent since its peak in August last year. Valeant plans to relaunch its sales effort for Addyi with an internal team it will build in the coming months, says a Bloomberg news report. In the meantime, the drug will still be available. Along with the 140 contract workers that make up the Addyi sales force, Valeant is firing about 140 employees across its dermatology, gastrointestinal and women’s health divisions, with dermatology taking the biggest hit. Valeant has about 22,000 employees. Alkem, Rusan and Anuh Pharma – data-integrity issues raise its ugly head yet again in India
Inspection at Alkem: In July 2015,
the European Union banned the marketing of around 700 generic medicines for alleged
manipulation of clinical trials conducted by India's pharmaceutical
research company GVK Biosciences. And this year, another laboratory is under
the lens of EU regulators.A routine inspection by the European Medicines Agency in
March 2015 of the Department of Bioequivalence of Alkem Laboratories,
a major generic drugs manufacturer in India, raised
concerns regarding study data used to support the marketing authorization
applications of some drugs in the EU. Rusan Pharma back in
news: In an inspection conducted in 2010 at Rusan Pharma’s facility in Gandhidham (India), the UK’s Medicines and Healthcare Regulatory Agency (MHRA) uncovered “evidence of fraudulent presentation of data” and determined that the site did not comply with Good Manufacturing Practices (GMPs). The same year, another unit of Rusan, located in Ankleshwar (India), did not meet GMP compliance standards during an inspection conducted by Romania’s National Agency for Medicines and Medical Devices. This week, Rusan was back in news. In January 2016, re-inspection by UK’s MHRA of the Gandhidham site found the Pharmaceutical Quality System “not operating in an adequate manner”. In addition, the inspection report mentions “there was not adequate evidence that the root causes of critical data integrity issues raised at the last inspection had been addressed.” Non-compliant
sourcing of drugs by Anuh Pharma: The French Health Agency’s inspection at Anuh Pharma’s
facility in Boisar (India) revealed the firm was sourcing commonly used Azithromycin
from a non-EU GMP compliant source (Hebei
Dongfeng Pharmaceutical Company Limited, China), micronizing the product and then directly exporting it to Europe under the manufacturer name, Anuh Pharma. In addition, several documents were found within a pile of
rubble which included an original batch repacking record. A large number of
active substances were manufactured at the site, such as chloramphenicol,
chloramphenicol
palmitate, erythromycin,
erythromycin
ethylsuccinate, roxithromycin,
ciprofloxacin
HCl etc. Catalent’s compliance problems delay OPKO’s new drug launchWith more than 40 manufacturing facilities around the
world, Catalent
is a preferred manufacturing partner for several major pharmaceutical companies
across the world. OPKO Health,
Inc., one of Catalent’s customers submitted its application for RAYALDEE® (calcifediol)
to the FDA. In the complete response letter (CRL) issued to the company, the
FDA indicated observations of
deficiencies at Catalent’s St. Petersberg, Florida, facility as a result of an FDA field inspection initiated on March 14, 2016, and had held up the new drug approval. According
to a news
report, OPKO revealed the deficiencies occurred at Catalent’s primary softgel development and manufacturing at St Petersburg, Florida, which was hit with a Form 483 being issued on March 25. Meanwhile,
Catalent began production of essential drugs at its French
plant, which had been suspended by France’s health regulator in November last year due to occurrence of out-of-place capsules in several product batches. Safety warnings for
new age diabetes drugs -- saxagliptin and alogliptin Last
year, the FDA had issued safety warnings on new age diabetes drugs called SLGT2
inhibitors (canagliflozin, dapagliflozin, and empagliflozin) and PharmaCompass
had asked the question, “Diabetes: Which new drug is the safest?”. At
the time Merck succeeded in demonstrating
the cardiovascular safety of Januvia®, which was not the case for other
products in the same categrory such as AstraZeneca’s Onglyza® (saxagliptin) and Takeda’s Nesina® (alogliptin). This
week the FDA issued a
safety warning on Onglyza® (saxagliptin) and Nesina® (alogliptin) as the
evaluation of two clinical trials determined that more patients
who received saxagliptin or alogliptin-containing medicines were hospitalized
for heart failure compared to patients who received an inactive treatment
called a placebo. Blockbuster drug
approval expected soon for non-alcoholic fatty liver The FDA reviewed the application of Intercept Pharmaceuticals Inc's liver drug, Obeticholic Acid (OCA) and did not raise any major red flags indicating a high
likelihood that it will get approved. While the drug is being reviewed for use in patients with
primary biliary cirrhosis, a rare liver disease, late-stage studies are
underway on the same drug to treat non-alcoholic steatohepatitis (NASH), which
has no approved treatment. Obeticholic acid (OCA) is listed as one of the top 10
possible blockbuster drugs by FierceBiotech with an expected
sales in 2020 of US $ 1.6 billion. Gilead is also actively building its liver disease pipeline
and this week, the company paid
US $ 400 million upfront to acquire an early-stage pipeline of liver
disease drugs from privately held Nimbus Therapeutics. Heart-disease science
turns over its headScience is supposed to be simple – for instance, LDL is bad cholesterol and HDL is good cholesterol. If a drug lowers the bad cholesterol and increases the good
one, the risk of heart disease should reduce significantly. Specialists were stunned by the results of a study
of 12,000 patients, announced on Sunday at the American College of Cardiology’s annual meeting: “There was no benefit from taking the drug, Evacetrapib.” The drug’s maker, Eli Lilly,
stopped
the study in October, citing futility, but it was not until Sunday’s meeting that cardiologists first saw the data behind that decision. As per the study, participants taking the drug saw their LDL
levels fall to an average of 55 milligrams per deciliter from 84. Their HDL
levels rose to an average of 104 mg per deciliter from 46. Yet 256 participants had heart attacks, compared with 255
patients in the group who were taking a placebo. Ninety-two patients taking the
drug had a stroke, compared with 95 in the placebo group. And 434 people taking
the drug died from cardiovascular disease, such as a heart attack or a stroke,
compared with 444 participants who were taking a placebo.
Impressions: 3042