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FDA Approvals 2024 & Potential First-in-Class Therapies to Watch in 2025

Release time:2025/1/22 18:25:47
Author:Huateng Pharma

In this article, we will review the key highlights of FDA-approved therapies in 2024 and explore potential first-in-class…

Recently, the Center for Drug Evaluation and Research (CDER) released 2024 New Drug Approvals Report. In 2024, CDER approved a total of 50 innovative therapies, surpassing the 10-year average of 47 approvals. Notably, more than 50% of these new drugs were developed for the treatment of rare diseases and rare cancers, highlighting the FDA's commitment to addressing unmet medical needs in these areas. In this article, we will review the key highlights of FDA-approved therapies in 2024 and explore potential "first-in-class" therapies expected to gain approval in 2025.

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Figure 1. CDER's noval drug approvals by year

Among the 50 noval approvals, small molecule drugs dominated, with 32 approvals (64%), reaffirming their role as a key driver of innovation. Protein-based therapies accounted for 16 approvals (32%), including 10 (20%) novel monoclonal antibodies and 3 (6%) bispecific antibodies. Additionally, there were 2 (4%) oligonucleotide-based therapies.

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Figure 2. CDER approvals by modality

Cancer remains the leading focus of drug development, with 13 new anti-cancer therapies approved. Rare disease treatments have also gained significant attention, with 13 approvals accounting for 26%, reflecting a growing emphasis on addressing the needs of underserved patient populations. Additionally, the cardiovascular, dermatological, and immunological fields each saw five new drug approvals, demonstrating balanced progress across a range of therapeutic areas.

Of the 50 new drugs approved by CDER, 24 were first-in-class therapies, accounting for 48%. The growing number of first-in-class therapies continues to push the boundaries of traditional treatments, setting a clear direction for future innovation.

Three Breakthrough Therapies

Xanomeline & Trospium Chloride (Cobenfy): The First Novel Schizophrenia Treatment in Decades

Current antipsychotic medications primarily work by blocking dopamine receptors to manage symptoms such as hallucinations, delusions, and other effects of schizophrenia. However, these treatments often lead to severe motor and metabolic side effects, increasing risks of heart disease and diabetes.

Developed jointly by Karuna and Bristol Myers Squibb, the fixed-dose combination drug Xanomeline & Trospium Chloride introduces a novel approach to treating schizophrenia. This dual M1/M4 muscarinic acetylcholine receptor (mAChR) agonist represents a groundbreaking mechanism of action for the disease, marking the first approval of such an innovative therapy in decades. While the drug does pose notable risks, including gastrointestinal side effects and potential liver damage, its development potential is significant. This was underscored by Bristol Myers Squibb's $14 billion acquisition of Karuna and KarXTin in 2024, signaling strong confidence in its future.

Resmetirom (Rezdiffra): The First FDA-Approved Therapy for NASH

Nonalcoholic steatohepatitis (NASH) is characterized by excessive fat accumulation in the liver, accompanied by inflammation that can lead to scarring and, in severe cases, liver failure.

Resmetirom (Rezdiffra), developed by Madrigal Pharmaceuticals, is the first therapy approved for NASH, now also referred to as Metabolic Dysfunction-Associated Steatohepatitis (MASH), with associated liver fibrosis. Resmetirom is an oral thyroid hormone receptor-beta (THR-β) agonist that addresses the metabolic underpinnings of the disease. It regulates lipid metabolism by lowering LDL cholesterol, triglycerides, and atherogenic lipoproteins. Additionally, it reduces liver fat by promoting fatty acid breakdown and stimulating mitochondrial biogenesis, thereby improving liver function and mitigating lipotoxicity.

This approval marks a major milestone in the NASH/MASH field, offering a groundbreaking therapeutic option for a condition with high unmet medical needs.

Lifileucel (Amtagvi): The First T-Cell Therapy for Solid Tumors

On February 16, 2024, the U.S. FDA granted accelerated approval to Amtagvi (lifileucel), a tumor-infiltrating lymphocyte (TIL) therapy developed by Iovance Biotherapeutics, for the treatment of advanced melanoma.

Amtagvi represents a significant milestone in cell therapy as the first approved TIL therapy and the first T-cell therapy approved for solid tumors. This breakthrough underscores the potential of cell-based treatments in addressing previously challenging cancer types, paving the way for further innovations in oncology.

Potential "First-in-Class" Therapies to Watch in 2025

Donidalorsen (Ionis Pharmaceuticals)

Target Indication: Hereditary Angioedema (HAE)

Donidalorsen is an RNA investigational LIgand-Conjugated Antisense (LICA) medicine designed to precisely target and silence the production of prekallikrein (PKK), interrupting the pathway that leads to HAE attacks.

In the Phase 3 clinical trial OASIS-HAE, patients with HAE were treated with donidalorsen (80 mg) via subcutaneous injection every four weeks (Q4W) (n=45) or every eight weeks (Q8W) (n=23), or placebo (n=22), over 24 weeks. The result demonstrate that 81% lower monthly HAE attack rate with donidalorsen Q4W compared to placebo over weeks one to 25 (p<0.001), and 55% reduction with Q8W (p=0.004).

Fitusiran (Sanofi, Alnylam Pharmaceuticals)

Target Indication: Hemophilia A and Hemophilia B

Fitusiran is an RNA interference (RNAi) therapy designed to prevent bleeding episodes in patients with Hemophilia A or B, regardless of whether they have developed clotting factor inhibitors, by working through a mechanism that lowers the production of antithrombin, a natural anticoagulant, thereby promoting better blood clotting.

In two Phase 3 clinical studies, patients treated with monthly subcutaneous injections of fitusiran experienced a 90% reduction in annualized bleeding rates compared to the control group.

Mirdametinib (SpringWorks Therapeutics)

Target Indication: Plexiform Neurofibromas Associated with Neurofibromatosis Type 1 (NF1-PN)

Mirdametinib is an oral allosteric small-molecule MEK inhibitor that targets MEK1 and MEK2. The U.S. FDA has accepted a New Drug Application (NDA) for mirdametinib in adults and children with NF1-PN. The NDA was granted Priority Review designation and has been given a Prescription Drug User Fee Act (PDUFA) action date of February 28, 2025.

In the pivotal Phase 2b ReNeu clinical trial, mirdametinib treatment showed an objective response rate of 52% in pediatric patients and 41% in adult patients. Both pediatric and adult patients in the ReNeu trial demonstrated statistically significant improvements in pain, quality of life, and physical function compared to baseline.

Plozasiran (Arrowhead Pharmaceuticals)

Target Indication: Familial Chylomicronemia Syndrome

Plozasiran is a potential "first-in-class" RNAi therapy designed to specifically target and reduce the production of apolipoprotein C-III (APOC3). APOC3 is expressed in liver and intestine and regulates triglyceride-rich lipoprotein (TRL) catabolism and anabolism. APOC3 increases plasma triglyceride levels by inhibiting LPL activity and increases both triglycerides and cholesterol by interfering with the clearance of TRLs and their remnants by hepatic LDLR and LRP1.  Plozasiran works by reducing the production of APOC3, thereby enabling the liver to increase its clearance of triglycerides and other fats.

Plozasiran has shown promising results in multiple clinical trials, particularly in the PALISADE study, where it reduced median triglyceride levels by 80% and acute pancreatitis by 83% compared to placebo, making it a potential game-changer for familial chylomicronemia syndrome (FCS).

Suzetrigine (Vertex Pharmaceuticals)

Target Indication: Moderate to Severe Acute Pain

Suzetrigine is an investigational oral, highly selective pain signal inhibitor that is selective for NaV1.8 relative to other NaV channels. NaV1.8 is a voltage-gated sodium channel primarily found in peripheral sensory neurons, and due to its significant role in transmitting pain signals, it is considered a key target for developing new pain treatments, validated by genetic studies linking its dysfunction to pain conditions.

Vertex Pharmaceuticals aims to develop a new class of drugs by selectively inhibiting NaV1.8. Compared to opioids, these drugs may provide effective pain relief while avoiding side effects such as addiction. The FDA has granted suzetrigine priority review and assigned a Prescription Drug User Fee Act (PDUFA) target action date of January 30, 2025.  .

Telisotuzumab Vedotin (AbbVie)

Target Indication: C-Met Overexpressing, Previously Treated Locally Advanced or Metastatic Non-Squamous Non-Small Cell Lung Cancer (NSCLC)

Telisotuzumab vedotin is an antibody-drug conjugate targeting c-Met, with the microtubule inhibitor MMAE as its cytotoxic payload. AbbVie has submitted a biologics license application (BLA) to the U.S. FDA, seeking accelerated approval for telisotuzumab vedotin to treat adult patients with locally advanced or metastatic non-squamous NSCLC who have c-Met overexpression and a wild-type epidermal growth factor receptor (EGFR). Data from a previously reported Phase 2 clinical trial showed an overall response rate of 35% in patients with high c-Met expression and 23% in those with moderate c-Met expression.

UGN-102 (UroGen Pharma)

Target Indication: Low-Grade, Intermediate-Risk Non-Muscle Invasive Bladder Cancer

UGN-102 is an innovative mitomycin-based bladder instillation therapy. It uses UroGen's proprietary RTGel technology, a hydrogel-based sustained release formulation that allows bladder tissue to remain exposed to mitomycin for a longer period, enabling non-surgical treatment of the tumor. In a Phase 3 clinical trial, patients treated with UGN-102 achieved a complete response rate of 79.6% (95% CI: 73.9-84.5) three months after the first instillation. The FDA is expected to announce its review results by June 13 of this year.

UX111 (Ultragenyx Pharmaceutical)

Target Indication: Type IIIA Mucopolysaccharidosis

UX111 is a novel in vivo gene therapy designed to treat Type IIIA Mucopolysaccharidosis. It aims to deliver a one-time intravenous dose using an AAV9 vector to transfer a transgene that expresses N-sulfoglucosamine sulfohydrolase (SGSH) to cells.

Ultragenyx Pharmaceutical has submitted a BLA to the U.S. FDA, seeking accelerated approval for UX111. Data from the pivotal Transpher A study showed that following treatment with UX111, patients experienced a rapid and sustained reduction in heparan sulfate (HS) levels in cerebrospinal fluid, and this sustained biomarker reduction was associated with improvements in long-term cognitive development.

 

References:
[1] Advancing Health Through Innovation: New Drug Therapy Approvals 2024. Retrieved January 20, 2025, from
https://www.fda.gov/media/184967/download?attachment
[2] Ten first-in-class drugs on track for FDA approval in 2025. Retrieved January 20, 2025, from https://www.labiotech.eu/best-biotech/first-in-class-drugs-to-watch-2025/