FDA Sets Review Date for Odronextamab to Treat Blood Cancers

The FDA has granted priority review for Regeneron’s biologics license application (BLA) for odronextamab to treat adult patients with relapsed/refractory follicular lymphoma (FL) or R/R diffuse large B-cell lymphoma (DLBCL). The target action date for the FDA decision is March 31, 2024.

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.

The BLA was supported by data from a phase 1 and pivotal phase 2 trial (ELM-1 and ELM-2). Results from these studies investigating odronextamab in both FL and DLBCL were presented lst year at the American Society of Hematology Annual Meeting.

In the phase 2 trial, 121 patients with follicular lymphoma were treated with a step-up regimen of odronextamab in the first cycle to help mitigate the risk of cytokine release syndrome before receiving the full dose of 80 mg. odronextamab resulted in a 82% objective response rate (ORR), with 75% achieving a complete response. The median duration of complete response. was 20.5 months. Median progression-free survival was 20 months.

Cytokine release syndrome was the most common adverse event and 68% of the cases were mild. Discontinuations due to an adverse events occurred in 11.5% of patients, and there were three deaths due to pneumonia, progressive multifocal leukoencephalopathy and systemic mycosis.

Additionally, the phase 2 enrolled 130 with diffuse large B-cell lymphoma who had not received prior CAR-T therapy. In these patients, odronextamab resulted in a 49% objective response rate, with 31% achieving a complete response. The median duration of complete response (mDOCR) was 18 months.

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.

Based on these data from the phase 2 trial, Regeneron has initiated a phase 3 program in earlier lines of therapy.