The US Food and Drug Administration (FDA) has issued Complete Response Letters (CRLs) for Regeneron's CD20xCD3 bispecific antibody odronextamab, declining to approve the therapy for two forms of non-Hodgkin lymphoma (NHL). The regulatory action impacts the company's applications for treating both relapsed/refractory follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) in patients who have progressed after at least two prior systemic therapies.
Regulatory Details and Impact
The FDA's decision centers specifically on the enrollment status of confirmatory trials that would support accelerated approval. Notably, Regeneron emphasized that the CRLs did not identify concerns regarding odronextamab's clinical efficacy, safety, trial design, labeling, or manufacturing processes.
The issue stems from the structure of Regeneron's OLYMPIA clinical trial program, which is investigating odronextamab across various NHL types and treatment lines. While dose-finding portions of these trials are ongoing, the FDA requires that confirmatory trial components also be actively enrolling, with agreed-upon completion timelines - a requirement aligned with the agency's Project Confirm initiative for accelerated approvals.
Market Context and Competition
The setback impacts Regeneron's strategy to establish odronextamab with the broadest label among CD20xCD3 bispecific antibodies. The current market landscape includes:
- Roche's Lunsumio (mosunetuzumab): Approved for third-line or later FL therapy
- Roche's Columvi (glofitamab): Indicated for DLBCL or large B-cell lymphoma arising from FL after two prior therapy lines
- AbbVie/Genmab's Epkinly (epcoritamab): Approved for DLBCL after two or more systemic therapies, with pending FL indication
Development Pipeline and Future Plans
Regeneron maintains an active development program for odronextamab, including:
- Ongoing trials in mantle cell lymphoma (MCL) and marginal zone lymphoma (MZL)
- Combination studies with CD22xCD28 bispecific REGN5837 in aggressive B-cell NHL
- European regulatory review currently in progress
The company plans to provide updated timeline information for resubmission later this year. Meanwhile, the CD20xCD3 therapeutic landscape continues to evolve, with all major players conducting trials to expand their respective drug indications across various NHL types and earlier treatment lines.
