European Commission Approves Regeneron's Ordspono for Lymphoma Treatment

The European Commission has granted approval for Ordspono (odronextamab), a new treatment developed by Regeneron, for adults with relapsed or refractory follicular lymphoma (FL) or diffuse large B-cell lymphoma (DLBCL) who have progressed after at least two prior systemic therapies. This approval comes just days after a competing therapy from Johnson & Johnson received the green light in the EU for the same indication.

Ordspono marks a significant milestone for Regeneron as it is the first bispecific antibody the company has introduced to the market. This drug is leading a pipeline of over a dozen clinical prospects for the biotech giant. The new medication joins a growing list of CD20xCD3 bispecific antibodies approved in Europe, including Tepkinly (epcoritamab) from Johnson & Johnson and Genmab, which was approved by the EU on August 19. Other CD20xCD3 bispecifics like Roche's Lunsumio (mosunetuzumab) and Columvi (glofitamab) received approvals in 2022 and 2023, respectively, for third-line treatments of FL and DLBCL.

These bispecific antibodies, including Gilead Sciences' Yescarta (axicabtagene ciloleucel), Novartis' Kymriah (tisagenlecleucel), and Bristol-Myers Squibb's Breyanzi (lisocabtagene maraleucel), are being positioned as alternatives to CAR-T cell therapies for non-Hodgkin lymphoma (NHL). Unlike CAR-T therapies, which involve complex production and administration processes and require in-hospital treatment, these new options could simplify treatment pathways for patients.

As cell therapies continue to advance along the treatment pathway, they may also emerge as viable options in post-CAR-T scenarios.

Ordspono's EU approval was based on results from the ELM-1 and ELM-2 clinical trials, which demonstrated an 80% overall response rate (ORR) among FL patients, with 73% achieving complete responses. In DLBCL patients, the ORR was approximately 50%, with about one-third of patients achieving a full recovery. Regeneron is also investigating odronextamab in other lymphoma types, including mantle cell lymphoma (MCL) and marginal zone lymphoma (MZL), and in combination with a CD22xCD28 bispecific antibody, REGN5837, in aggressive B-cell NHL.

Despite the recent European approval, the FDA rejected Regeneron's application for odronextamab earlier this year, citing that the company had not yet initiated the necessary trials to confirm accelerated approvals for the two applications. Regeneron emphasized that there were no issues related to "clinical efficacy or safety, trial design, labeling, or manufacturing," suggesting that the delay might not be prolonged.

Industry analysts from Jefferies have previously indicated that Epkinly (epcoritamab) from Johnson & Johnson is expected to lead the CD20xCD3 bispecific class, with projected annual sales of $2.75 billion. In comparison, Roche's combined sales for its two medications are expected to reach approximately $2 billion. Odronextamab is seen as lagging behind its competitors, partly due to its delayed market entry, association with some treatment-related fatalities during clinical trials, a period of clinical hold during its development, and comparatively modest DLBCL data.

FL and DLBCL are the most common subtypes of B-cell non-Hodgkin lymphoma (NHL), with approximately 163,000 DLBCL cases and 120,000 FL cases diagnosed annually in Europe.

George Yancopoulos, Regeneron's Chief Scientific Officer, expressed optimism about the approval and the future of Ordspono, stating, "Building upon this approval, we are excited about our OLYMPIA program, which includes multiple phase 3 trials investigating Ordspono as a monotherapy and in various combinations, in earlier lines of therapy."