The U.S. Food and Drug Administration (FDA) is poised to make several key decisions in the first quarter of 2025 that could significantly impact treatment paradigms across various medical fields. These include potential approvals for new therapies targeting Alzheimer's disease, breast cancer, acute pain, and rare genetic disorders.
Leqembi's Monthly Maintenance Dose Awaits FDA Nod
Biogen and Eisai are awaiting the FDA's decision on a monthly intravenous (IV) maintenance regimen for their Alzheimer's disease therapy, Leqembi (lecanemab), with a PDUFA date set for January 25. Leqembi, already approved for patients with mild cognitive impairment or mild dementia, is currently administered bi-weekly. The proposed monthly regimen aims to sustain therapeutic levels of the drug, targeting toxic protofibrils to prevent nerve damage even after amyloid-beta plaque clearance. This application is supported by data from Phase IIb Study 201, its open-label extension, and the Phase III Clarity AD trial. Eisai lowered its full fiscal year sales forecast for Leqembi to $280 million, citing infrastructure challenges. Despite this, demand remains strong, with approximately 6,000 patients awaiting initiation on the therapy.
Dato-DXd for Breast Cancer Faces Regulatory Review
AstraZeneca and Daiichi Sankyo anticipate an FDA decision by January 29 regarding their Biologics License Application (BLA) for datopotamab deruxtecan (Dato-DXd), an antibody-drug conjugate (ADC) intended for metastatic, HR-positive, HER2-negative breast cancer. Phase III TROPION-Breast01 study data showed a 37% reduction in the risk of death or disease progression compared to chemotherapy. However, follow-up data indicated no significant overall survival benefit. Dato-DXd targets the TROP2 protein, delivering an exatecan derivative payload directly to cancer cells. The most common grade 3 or higher side effects included neutropenia, fatigue, and anemia.
Vertex's Non-Opioid Painkiller Seeks Approval
Vertex Pharmaceuticals is advancing suzetrigine, a non-opioid analgesic, for moderate-to-severe acute pain, with an FDA decision expected by January 30. Suzetrigine selectively inhibits the NaV1.8 voltage-gated sodium channel, a pain target found on peripheral neurons involved in pain signaling. Phase II and III trials, including NAVIGATE 1 and NAVIGATE 2, demonstrated statistically significant pain score improvements in patients undergoing bunionectomy and abdominoplasty. Specifically, pain scores improved by 48.4 points after abdominoplasty and 29.3 points after bunionectomy compared to placebo. If approved, suzetrigine would be the first new drug class for acute pain in over two decades.
Alnylam's Amvuttra for Transthyretin Amyloid Cardiomyopathy
Alnylam is seeking to expand the indication of Amvuttra to include transthyretin amyloid cardiomyopathy (ATTR-CM), with a decision expected by March 23. Amvuttra, an RNA interference treatment, reduces TTR protein levels, thereby decreasing TTR deposits in the heart. Phase III HELIOS-B study data showed favorable effects on survival, cardiovascular events, functional capacity, and quality of life in ATTR-CM patients, with a 28% reduction in the composite outcome of all-cause mortality and recurrent cardiovascular events.
SpringWorks' Mirdametinib for Neurofibromatosis
SpringWorks Therapeutics' mirdametinib is under priority review for the treatment of adult and pediatric patients with neurofibromatosis type 1-associated plexiform neurofibromas (NF1-PN), with a decision due on February 28. Mirdametinib, a MEK inhibitor, demonstrated a 41% objective response rate in adults and 52% in pediatric patients in the Phase 2b ReNeu trial. The drug is administered orally in 28-day cycles. Neurofibromatosis type 1 (NF1) is a rare genetic disorder of the nervous system causing tumors to grow on nerves. These tumors can lead to significant disfigurement and often cause chronic, debilitating pain. Individuals with NF1 may also face a reduced life expectancy, typically 8 to 15 years shorter than that of the general population, due to the complications associated with the condition.
Other Key FDA Decisions
Several other notable FDA decisions are anticipated in early 2025, including Supernus Pharmaceuticals' SPN-830 for Parkinson's disease, Indivior's SUBLOCADE label expansion for opioid use disorder, GSK's 5-in-1 MenABCWY vaccine for invasive meningococcal disease, and Ono Pharmaceutical's Vimseltinib for tenosynovial giant cell tumor.
