Regeneron tries again with lymphoma bispecific in US

A year after the FDA rejected its marketing application for CD20xCD3 bispecific antibody odronextamab to treat two common forms of non-Hodgkin lymphoma (NHL), Regeneron has refiled the drug for just one of them.

The FDA has accepted and begun its review of odronextamab for relapsed or refractory follicular lymphoma (FL) after two or more lines of systemic therapy and is due to deliver a verdict on the application by 30th July.

Regeneron had originally submitted odronextamab for accelerated approval as a third-line therapy for both FL and relapsed/refractory diffuse large B-cell lymphoma (DLBCL), but both filings were turned down by the FDA in March 2024 due to the status of trials that would be needed to convert those to full approvals. FL and DLBCL are the two most common subtypes of B-cell NHL.

In a statement, Regeneron said the resubmission of the bispecific in FL comes after it achieved an enrolment target in the phase 3 OLYMPIA-1 trial, which is comparing odronextamab to standard treatment with rituximab and chemotherapy in previously untreated FL.

In December, Regeneron presented initial results from the safety lead-in portion of OLYMPIA-1 at the American Society of Haematology meeting, showing that odronextamab monotherapy achieved complete responses (CR) in all 12 evaluable patients, while rituximab/chemo typically achieves CR in around two-thirds of patients.

A few months after the FDA rejection, odronextamab was cleared in the EU under the Ordspono trade name as a third-line therapy for both FL and DLBCL, based on data from the phase 2 ELM-1 and ELM-2 trials, which revealed an 80% overall response rate (ORR) with the drug in FL and 50% in DLBCL. So far, however, it has not been approved in any other world market.

Ordspono is one of a handful of CD20xCD3 bispecifics being rolled out for NHL, alongside Johnson & Johnson/Genmab and AbbVie's Epkinly/Tepkinly (epcoritamab) and Roche's Lunsumio (mosunetuzumab) and Columvi (glofitamab).

In the US, Epkinly is approved as a third-line therapy for FL and DLBCL, while Lunsumio and Columvi are cleared for third-line treatment of FL and DLBCL, respectively.

All of the drugs are being positioned as off-the-shelf alternatives to CAR-T cell therapies for NHL, such as Gilead Sciences' Yescarta (axicabtagene ciloleucel), Novartis' Kymriah (tisagenlecleucel), and Bristol-Myers Squibb's Breyanzi (lisocabtagene maraleucel), which have complex manufacturing and administration procedures and require in-hospital care.

They can also be options for the post-CAR-T setting as the cell therapies move earlier in the treatment pathway.