FDA Issues CRL for Odronextamab for Lymphoma Indications

The FDA has issued complete response letters (CRLs) for Regeneron’s biologics license application (BLA) for odronextamab in patients relapsed/refractory (R/R) follicular lymphoma (FL) and in R/R diffuse large B-cell lymphoma (DLBC).

Regeneron officials said in a press release that regulators want to address an issue related enrollment status of the confirmatory trial. The company has been actively enrolling patients in multiple phase 3 trials for odronextamab as part of the OLYMPIA program. The program both dose-finding and confirmatory portions. Enrollment in the dose-finding portion has begun, but the CRLs indicate that the confirmatory portions of these trials should be under way and that the timelines to completion be agreed prior to resubmission.

Follicular lymphoma and diffuse large B-cell lymphoma are the two most common subtypes of B-cell non-Hodgkin lymphoma. FL is a slow-growing subtype, and although many patients are responsive to initial treatment, about 20% are expected to relapse within two years. DLBCL is an aggressive subtype, with up to 50% of high-risk patients experiencing progression after first-line treatment.

Odronextamab is an investigational CD20xCD3 bispecific antibody designed to target both CD20 on cancer cells and CD3-expressing T cells.

Related: FDA Sets Review Date for Odronextamab to Treat Blood Cancers

FDA had set a target action date for March 31, 2024. The submission was based on data data from a phase 1 and pivotal phase 2 trial (ELM-1 and ELM-2). In the phase 2 trial with 121 patients with follicular lymphoma, odronextamab resulted in a 82% objective response rate, with 75% achieving a complete response. The phase 2 trial also enrolled 130 with diffuse large B-cell lymphoma. In these patients, odronextamab resulted in a 49% objective response rate, with 31% achieving a complete response.

Cytokine release syndrome was the most common adverse event, and 64% of cases were mild. Discontinuations due to an adverse event occurred in 10% of patients, and there were five deaths due to pneumonia, COVID-19 and pseudomonal sepsis.