Odronextamab Gains FDA Review for Hard-to-Treat Relapsed/Refractory Follicular Lymphoma

Regeneron Pharmaceuticals, announced that the US FDA accepted its resubmitted Biologics License Application for odronextamab, a CD20xCD3 bispecific antibody, relapsed/refractory (R/R) follicular lymphoma (FL) after two or more lines of systemic therapy. Clinical trials (ELM-1, ELM-2) reported high response rates but serious adverse events. Confirmatory Phase 3 trials, including OLYMPIA-1, aim to verify effectiveness. The decision is expected by July, 2025 and approval could broaden treatment options.

Overcoming Earlier Hurdles

Last year, the FDA sent the company what is known as a “complete response letter,” which flags outstanding issues to address before approval can be granted. According to Regeneron, the only obstacle highlighted was a requirement that enough people be enrolled in a confirmatory trial of odronextamab. This trial, called OLYMPIA-1, has now met its enrolment target, allowing the application to move forward.

Strong Early Data

The BLA resubmission is supported by data from the Phase 1 and pivotal Phase 2 trials (ELM-1 and ELM-2), which demonstrated an overall response rate of 80% (n=103), with 74% (n=95) achieving a complete response.

However, serious adverse events occurred in 67% of patients, with cytokine release syndrome, COVID-19, and pneumonia each affecting 10% or more of those involved. Despite these risks, experts hope that odronextamab could offer a fresh option to patients who have few remaining treatment avenues.

European Approval Already Secured

Odronextamab, known as Ordspono™ in the European Union, is already approved there to treat R/R follicular lymphoma or diffuse large B-cell lymphoma (DLBCL). Its full safety and effectiveness in other regions, including the US, are still under review.

How Odronextamab Works

Odronextamab is a CD20xCD3 bispecific antibody, designed to “bridge” two critical cells:

• CD20 on cancer cells
• CD3 on T cells (a key component of the immune system)

By linking these targets, the drug aims to help T cells recognize and destroy malignant B cells more efficiently.

Ongoing Trials and Future Plans

Beyond the ELM-1 and ELM-2 studies, odronextamab is undergoing extensive testing in other B-cell malignancies. These include:

• OLYMPIA-1, a Phase 3 trial comparing odronextamab alone with rituximab plus chemotherapy, which also serves as the confirmatory study for FDA approval in FL.
• OLYMPIA-2, a Phase 3 trial assessing odronextamab in combination with chemotherapy against rituximab-based standard-of-care treatments.

Should odronextamab secure approval later this year, oncologists say it could add a valuable tool for people with limited treatment options.