5 FDA Decisions to Watch in Q1 2025

The FDA closed out a productive 2024 with 55 new drug approvals. Among the newly approved treatments were several with novel mechanisms, such as Bristol-Myers Squibb's Cobenfy, the first new mechanism drug for schizophrenia in over 30 years; the first biologic approved for chronic obstructive pulmonary disease (COPD), Dupixent from Sanofi and Regeneron; and Madrigal Pharmaceuticals' Rezdiffra, the first-ever treatment for metabolic dysfunction-related fatty liver disease. Additionally, Eli Lilly's Kisunla offers a much-needed alternative for treating Alzheimer's disease related to amyloid protein.

The gene therapy field also saw significant progress in 2024, including Pfizer's Beqvez for hemophilia B and PTC Therapeutics' Kebilidi, the first-ever gene therapy directly used in the brain to treat L-amino acid decarboxylase deficiency.

Looking ahead, the FDA is set to make several important regulatory decisions that could have profound implications for the industry and clinical practice. Below are the top five anticipated regulatory decisions for Q1 2025, summarized by BioSpace:

1. Leqembi

Developers: Biogen and Eisai

Indication: IV maintenance for early Alzheimer’s disease

PDUFA: January 25

Biogen and Eisai are awaiting FDA approval for the monthly IV maintenance regimen of Leqembi (lecanemab), their Alzheimer’s treatment. Leqembi is the first FDA-approved amyloid antibody treatment for Alzheimer’s disease, currently administered as an IV infusion every two weeks. The new monthly regimen aims to maintain drug levels in the body to inhibit toxic protofibrils that could cause neurological damage after β-amyloid plaque removal. Data from the Phase IIb 201 study and the Phase III ClarityAD study support this application. The companies are also progressing a subcutaneous formulation of Leqembi. However, the product has faced infrastructure and launch challenges, and its sales forecast has been revised down.

2. Dato-DXd

Developers: AstraZeneca and Daiichi Sankyo

Indication: Metastatic, HR-positive, HER2-negative breast cancer

PDUFA: January 29

The FDA is expected to announce its decision on the biologics license application (BLA) for datopotamab deruxtecan (Dato-DXd), an antibody-drug conjugate targeting the TROP2 protein, which is highly expressed in various cancers. Clinical results have shown mixed outcomes, with the ADC reducing the risk of death or disease progression by 37% in the TROPION-Breast01 trial compared to chemotherapy. However, follow-up data indicated no significant improvement in overall survival. The drug’s safety profile is generally favorable, with common adverse effects including neutropenia, fatigue, and anemia.

3. Suzetrigine

Developer: Vertex Pharmaceuticals

Indication: Moderate to severe acute pain

PDUFA: January 30

Vertex Pharmaceuticals is advancing suzetrigine, a non-opioid analgesic targeting the NaV1.8 voltage-gated sodium channel, for moderate to severe acute pain. This oral pain signal inhibitor has shown promising results in Phase III trials for postoperative pain, demonstrating significant pain reduction compared to placebo. Suzetrigine may offer an alternative to opioids, potentially providing pain relief without the risk of addiction.

4. Amvuttra

Developer: Alnylam Pharmaceuticals

Indication: Transthyretin amyloidosis cardiomyopathy (ATTR-CM)

PDUFA: March 23

Amvuttra, an RNA interference therapy, is designed to treat ATTR-CM, a condition caused by the accumulation of transthyretin (TTR) protein in organs. Amvuttra has shown favorable outcomes in clinical trials, reducing all-cause mortality and recurrent cardiovascular events by 28% in patients with ATTR-CM. If approved, it will become the first RNA interference therapy for this condition.

5. Fitusiran

Developer: Sanofi

Indication: Hemophilia A or B

PDUFA: March 28

Fitusiran, a targeted siRNA therapy developed by Sanofi and Alnylam, aims to reduce bleeding events in hemophilia A and B patients by decreasing the production of antithrombin, thereby restoring the balance between clotting factors and anticoagulant factors. Clinical trials have demonstrated a significant reduction in bleeding rates, and if approved, fitusiran could offer a new treatment option for hemophilia patients, with monthly subcutaneous injections providing convenient bleeding risk control.

Reference

[1] https://www.biospace.com/fda/5-fda-decisions-to-watch-in-q1