FDA Decisions and Clinical Trials Shape Q4 Pharmaceutical Landscape

As the pharmaceutical industry enters the final quarter of 2025, a series of highly anticipated FDA decisions and clinical trial results are poised to significantly impact treatment landscapes across multiple therapeutic areas. From potential comebacks to groundbreaking firsts, Q4 promises to be a pivotal period for several key players in the sector.

Regeneron Awaits Verdict on High-Dose Eylea

Regeneron Pharmaceuticals is anticipating FDA decisions on two applications for its high-dose formulation of Eylea (aflibercept) in the fourth quarter. The company is seeking approval for macular edema after retinal vein occlusion (RVO) and a monthly dosing regimen across all approved indications.

The regulatory review was extended due to manufacturing issues at a third-party facility previously owned by Catalent, which was acquired by Novo Nordisk's parent company in February 2024. Despite these setbacks, Regeneron remains optimistic about a favorable outcome, with CEO Leonard Schleifer stating, "We are expecting, once the resolution of the filling issues has occurred, to receive favorable action, we hope, from the FDA."

The high-dose Eylea application is supported by data from the Phase III QUASAR study, which demonstrated non-inferiority to the standard-dose version in treating macular edema after RVO.

GSK's Blenrep Seeks Market Return

By October 23, the FDA is expected to decide on GSK's application to reintroduce Blenrep (belantamab mafodotin) as a second-line treatment for relapsed/refractory multiple myeloma. Blenrep, an antibody-drug conjugate targeting CD38, was originally approved in August 2020 but was withdrawn from the market in November 2022 after failing its confirmatory Phase III study.

GSK's comeback bid is supported by data from two Phase III trials, DREAMM-7 and DREAMM-8. DREAMM-7 showed a 59% reduction in the risk of death or disease progression compared to a regimen using Johnson & Johnson's Darzalex, while DREAMM-8 demonstrated significantly better progression-free survival versus Takeda's Velcade.

However, the FDA's internal reviewers have raised concerns about high rates of ocular toxicity and dose modifications in both trials. An external advisory committee voted 7-1 against Blenrep in July, citing an unfavorable benefit-risk profile.

Potential Firsts in CAR-T and RNAi Therapies

Bristol Myers Squibb's CAR-T therapy Breyanzi (lisocabtagene maraleucel) could become the first in its class approved for marginal zone lymphoma (MZL), with an FDA decision expected by December 5. The application is based on the Phase II TRANSCEND FL study, which showed a 95.5% overall response rate in MZL patients.

Meanwhile, Arrowhead Pharmaceuticals is awaiting a November 18 decision on plozasiran, an RNA interference therapeutic for familial chylomicronemia syndrome (FCS). If approved, it would be the first treatment specifically indicated for this ultra-rare genetic disorder. The Phase III PALISADE trial demonstrated an 80% reduction in triglyceride levels with the proposed commercial dose of plozasiran.

These potential approvals underscore the ongoing innovation in cell and gene therapies, as well as the industry's focus on addressing rare and ultra-rare diseases with high unmet medical needs.