DATA COMPILATION #PharmaFlow

FDA approvals slump 19% in H1 2024; NASH, COPD, PAH get new treatment options

The first half of 2024 saw a significant slowdown in approvals of new drugs and biologics by the US Food and Drug Administration (FDA) compared to the same period last year.FDA’s Center for Drug Evaluation and Research (CDER) approved 21 drugs in H1 2024, reflecting a 19 percent decrease from the 26 approvals granted in H1 2023. Of them, 81 percent (17) were first-in-class drugs (therapies that use a new and unique mechanism of action), while small molecules made up for 67 percent (14) of the total drugs approved.Similarly, the Center for Biologics Evaluation and Research (CBER) granted approvals to only eight biologics, as compared to 10 in H1 2023.Health Canada also saw a drop in drug approvals as only 10 drugs were okayed in H1 2024, as opposed to 13 approvals in H1 2023.The European Medicines Agency (EMA) saw a marginal rise in drug authorizations at 15 for H1 2024 as compared to 14 approvals in H1 2023. Interestingly, the EMA also saw a surge in pending decisions (applications under review) — from two in H1 2023 to 14 in H1 2024.View New Drug Approvals in H1 2024 with Estimated Sales (Free Excel Available)Merck, Madrigal, Verona bag approvals for breakthrough meds; Lilly’s donanemab okayedThe first half saw some closely watched drugs win regulatory approvals. FDA approved a breakthrough therapy from Merck — Winrevair (sotatercept) — that treats adults with hypertension caused by the constriction of arteries in the lungs, known as pulmonary arterial hypertension (PAH).Merck had acquired Winrevair through its US$ 11.5 billion acquisition of Acceleron Pharma in 2021. The therapy is set to generate nearly US$ 3 billion in global peak sales by 2028. Another breakthrough therapy approved in H1 2024 is Madrigal’s Rezdiffra (resmetirom), the first FDA-approved treatment for adults with the common fatty liver disease — nonalcoholic steatohepatitis (NASH). Rezdiffra is expected to touch sales of US$ 2.1 billion by 2028.The agency also approved the first maintenance treatment for chronic obstructive pulmonary disease (COPD) in over 20 years — Verona’s Ohtuvayre. The drug has a novel mechanism of action and is the first inhaled maintenance treatment for COPD. Approved in June by the FDA, Ohtuvayre is forecast to bring in global sales of US$ 1.5 billion by 2030.The approval of Eli Lilly’s donanemab was surprisingly delayed, and finally came through on July 2 after an FDA advisory committee voted unanimously in favor of its benefits outweighing its risks. To be sold as Kinsula, the Alzheimer's drug is estimated to bring in US$ 2.2 billion in sales by 2028.Across the pond, EMA approved Novo Nordisk’s weekly insulin injection Awiqli (insulin icodec). The replacement insulin in Awiqli acts in the same way as the body’s own insulin and helps glucose enter cells from the blood. Meanwhile, FDA rejected this once-a-week insulin earlier this month and has requested information related to the manufacturing process.View New Drug Approvals in H1 2024 with Estimated Sales (Free Excel Available) ImmunityBio, Geron, Day One win approvals for their oncology drugsIn what marks the first approval for ImmunityBio, FDA greenlit Anktiva (nogapendekin alfa inbakicept-pmln) as part of a combination therapy to treat a type of bladder cancer. Anktiva is a next-generation immunotherapy that creates long-term immunity by activating the so-called natural killer (NK) cells and T-cells. It will compete with Merck’s Keytruda. Anktiva’s yearly sales by 2030 are expected to be around US$ 1.7 billion.BeiGene’s PD-1 blocker Tevimbra (tislelizumab) got the go-ahead from the FDA as the treatment for adult patients with unresectable or metastatic esophageal squamous cell carcinoma (ESCC) after prior systemic chemotherapy that did not include a PD-(L)1 inhibitor. Tevimbra’s 2028 global sales are forecast to bring in US$ 1.6 billion.FDA signed off on Geron’s Rytelo (imetelstat) for treating transfusion-dependent anemia in patients with low- to intermediate-risk myelodysplastic syndromes (MDS), a group of blood cancers. This was Geron’s maiden approval and Rytelo is expected to bring in US$ 1.3 billion by 2030.Day One Biopharmaceuticals’ Ojemda (tovorafenib) was granted FDA’s accelerated approval to treat certain types of pediatric brain cancer. This is the first FDA approval of a systemic therapy for treating what is the most common form of childhood brain tumor, including fusions. Ojemda is forecast to bring in US$ 1 billion in sales by 2030.FDA granted accelerated approval to Amgen’s Imdelltra (tarlatamab-dlle) for adults in advanced stages of small cell lung cancer (SCLC) that has proven to be hard to treat or has worsened despite platinum-based chemotherapy. Imdelltra is expected to bring in annual sales of US$ 975 million by 2030.View New Drug Approvals in H1 2024 with Estimated Sales (Free Excel Available) Infectious disease drugs from Basilea, Merck, rare disease med from Ipsen bag approvalsAfter oncology, infections and infectious diseases, and rare diseases were the two therapeutic areas that saw the second and third most approvals, respectively. FDA approved Basilea Pharmaceutica’s Zevtera (ceftobiprole medocaril sodium for injection), an antibiotic for bacterial infections including multidrug-resistant strains.The US agency also approved Merck’s next-generation vaccine designed to protect adults from pneumococcus bacteria that causes serious illnesses and pneumonia. The jab, known as Capvaxive, helped produce an immune response against all 21 variations (serotypes) of the bacteria that it targeted. These 21 strains account for about 85 percent of invasive pneumococcal disease cases in adults aged 65 and above. FDA also approved Moderna’s mRESVIA, a messenger RNA-based (mRNA) respiratory syncytial virus (RSV) vaccine, to protect adults aged 60 years and older from lower respiratory tract disease caused by the syncytial virus. This is the first non-Covid mRNA vaccine to be approved in the US.The agency granted accelerated approval to Ipsen’s Iqirvo (elafibranor) to treat primary biliary cholangitis (PBC), a rare liver disease. This is the first new medicine approved in nearly a decade for the treatment of PBC. Orchard Therapeutics’ Lenmeldy secured FDA approval to become the first gene therapy in the US for a rare pediatric disorder, known as metachromatic leukodystrophy (MLD). The debilitating hereditary disease affects the brain and the nervous system and causes loss of cognitive and motor functions and early death.View New Drug Approvals in H1 2024 with Estimated Sales (Free Excel Available) Our viewThe increased momentum of drug approvals witnessed after the pandemic appears to have slowed down, but what’s encouraging is the increase in first-in-class therapies, cancer drugs and promising new treatment options for a range of conditions such as PAH, NASH, and COPD.The second half has already kicked off with the approval of Lilly’s donanemab. And there are several pathbreaking drugs likely to be approved soon, such as Karuna Therapeutics’ schizophrenia drug KarXT and BridgeBio’s heart drug acoramidis. There is every possibility that new drug approvals will spring back up in H2 2024.

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Pipeline Prospector Oct 2024: Lundbeck acquires Longboard for US$ 2.6 bn; molecular glue degrader tech witnesses dealmaking

In October, several pharma companies posted their third quarter (Q3) results. Drugmakers like Pfizer, BMS, Roche, Novartis, Sanofi, Merck and Incyte reported higher-than-expected Q3 earnings, beating analyst expectations. Despite these healthy results, pharma indices continued on their downward journey that had begun in September. The Nasdaq Biotechnology Index (NBI) dropped 2.6 percent from 4,771.85 to 4,650.07. The SPDR S&P Biotech ETF (XBI) fell 1.6 percent from 98.61 to 97.03, and the S&P Biotechnology Select Industry Index (SPSIBI) decreased 1.9 percent from 7,707.4 to 7,561.29. Access the Pipeline Prospector Dashboard for October 2024 Newsmakers (Free Excel) Lundbeck buys Longboard, AbbVie picks up Aliada, Merck acquires Modifi in US$ 1 bn+ deals In mergers and acquisitions, Denmark’s Lundbeck agreed to buy California-based Longboard Pharmaceuticals for US$ 2.6 billion. The acquisition centers around bexicaserin, a promising phase 3 candidate for rare epilepsies including Dravet syndrome and Lennox-Gastaut syndrome, with Lundbeck projecting potential peak sales of US$ 1.5 billion to US$ 2 billion for this asset. AbbVie acquired Boston-based Aliada Therapeutics for US$ 1.4 billion after reportedly outbidding at least three other drugmakers. The acquisition brings innovative blood-brain barrier technology to AbbVie’s portfolio, along with ALIA-1758, a phase 1 compound showing potential as a best-in-class therapy for Alzheimer’s disease. AbbVie also partnered with EvolveImmune Therapeutics in a potential US$ 1.4 billion deal (plus US$ 65 million upfront) to develop next-generation cancer biotherapeutics. The collaboration will leverage EvolveImmune’s innovative T-cell engager platform to create multispecific biologics targeting various oncology indications. Merck bolstered its oncology pipeline through the acquisition of Modifi Biosciences in a deal valued up to US$ 1.3 billion. The acquisition targets novel DNA modification therapeutics for challenging brain tumors, particularly glioblastomas. Merck also entered into a potential US$ 1.9 billion deal with Mestag Therapeutics to explore fibroblast therapies for inflammatory diseases, leveraging Mestag’s innovative platform. Access the Pipeline Prospector Dashboard for October 2024 Newsmakers (Free Excel) Pfizer, Novartis, Biogen sign molecular glue degrader deals; Astra in US$ 2 bn pact with CSPC There were at least three deals signed in October in the molecular glue degrader technology space. These degraders represent a novel therapeutic approach by facilitating the degradation of disease-causing proteins that are otherwise difficult to target with conventional drugs. First, Pfizer partnered Triana Biomedicines in a deal potentially exceeding US$ 1.5 billion, focusing on cancer applications. Second, Novartis committed US$ 150 million upfront to Monte Rosa Therapeutics in a deal worth up to US$ 2.25 billion. And Biogen tied up with Neomorph, pledging up to US$ 1.45 billion for neurological and immunological applications. Among other deals, AstraZeneca entered into a US$ 2 billion licensing agreement with CSPC Pharmaceutical Group for a novel lipid-lowering therapy, while Recordati acquired global rights to Sanofi’s Enjaymo for US$ 825 million upfront, with additional milestone payments of up to US$ 250 million. The Recordati-Sanofi deal focuses on cold agglutinin disease (CAD), a rare autoimmune disorder, and includes rights to sutimlimab, the first and only targeted therapy for CAD patients. Roche demonstrated its commitment to gene therapy advancement by expanding its collaboration with Dyno Therapeutics, committing over US$ 1 billion for adeno-associated virus (AAV) vector development, with an upfront payment of US$ 50 million. This expanded partnership builds on their initial 2020 collaboration and aims to accelerate the development of innovative gene therapies for neurological diseases. Access the Pipeline Prospector Dashboard for October 2024 Newsmakers (Free Excel) AbbVie wins FDA nod for subcutaneous Parkinson’s drug; Roche med okayed for breast cancer October marked significant advances in the treatment of several major diseases. FDA approved AbbVie’s Vyalev for advanced Parkinson’s disease. This innovative therapy, utilizing foscarbidopa and foslevodopa prodrugs, delivers round-the-clock symptom control through subcutaneous infusion. The treatment represents a major advancement in managing motor fluctuations in late-stage patients, with market analysts projecting peak sales exceeding US$ 2 billion. In the oncology space, a historic milestone was reached with FDA’s approval of Vyloy, the world’s first therapy targeting CLDN18.2 proteins in gastric cancer. Developed by Astellas, the drug was approved for use in combination with chemotherapy for treating advanced gastric or gastroesophageal junction adenocarcinoma in adults with HER2-negative, CLDN18.2-positive tumors. This approval validates Astellas’ strategic US$ 1.4 billion acquisition of Ganymed Pharmaceuticals in 2016. Roche strengthened its position in breast cancer treatment with the approval of Itovebi, an oral PI3K inhibitor for first-line treatment of advanced hormone receptor-positive, HER2-negative breast cancer with PIK3CA mutation. This approval positions Itovebi as a strong competitor to existing treatments like Novartis' Piqray and AstraZeneca's Truqap, with Roche projecting annual peak sales of US$ 2.3 billion. Novartis expanded the reach of its leukemia treatment Scemblix through an accelerated approval for newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase. This expansion significantly increases the eligible patient population by approximately four times, building on its existing approval as a third-line treatment. Pfizer expanded its presence in the respiratory syncytial virus (RSV) market as FDA broadened the approval of Abrysvo to include at risk adults aged 18 to 50 years, making it the first and only RSV vaccine authorized for this population. In hematology, Pfizer secured approval for Hympavzi marking its second hemophilia approval in six months. This approval follows the earlier authorization of Pfizer’s one-time gene therapy Beqvez for hemophilia B in April. Iterum Therapeutics received FDA approval for its new oral antibiotic, Orlynvah, designed to treat uncomplicated urinary tract infections (uUTIs) in adult women who have limited or no alternative oral antibacterial treatment options. This marks the first US approval for an oral penem antibiotic. Access the Pipeline Prospector Dashboard for October 2024 Newsmakers (Free Excel) Gilead withdraws Trodelvy, J&J discontinues late-stage study of its bladder cancer candidate In a notable development for bladder cancer treatment, Gilead Sciences announced the withdrawal of Trodelvy from the US market after the targeted therapy, which received accelerated FDA approval in 2021 for metastatic urothelial cancer, failed to demonstrate survival benefits in a crucial confirmatory study. Johnson & Johnson decided to discontinue the late-stage study of TAR-200, their investigational bladder cancer therapy, after interim analysis showed no superior benefits compared to standard chemo-radiation therapy. In neurology, Marinus Pharmaceuticals faced disappointment when their phase 3 trial of oral ganaxolone (Ztalmy) failed to meet its primary endpoint in reducing seizures associated with tuberous sclerosis complex (a genetic disorder). Marinus’ stock fell nearly 100 percent in October. Access the Pipeline Prospector Dashboard for October 2024 Newsmakers (Free Excel) Our view The last quarter was a good one for several drugmakers. Pfizer saw a surge in sales of its Covid drug Paxlovid to US$ 2.7 billion, encouraging it to up its guidance for Covid-related sales from US$ 8.5 billion to US$ 10.5 billion. For BMS, blockbusters like blood thinner Eliquis and cancer treatment Revlimid continued to bring in revenue. Merck’s growth was driven by the world’s top-selling drug, Keytruda, which saw revenue jump 17 percent compared to Q3 2023, beating analysts’ estimates. In a nutshell, the robust Q3 earnings of major pharma companies signals strong industry fundamentals, the volatility in pharma indices notwithstanding. Access the Pipeline Prospector Dashboard for October 2024 Newsmakers (Free Excel)

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