Regeneron anticipates EU approval for lymphoma drug after US rejection

On Monday, the European Commission approved Regeneron’s Ordspono (odronextamab), marking it the second CD20xCD3-targeting bispecific antibody to receive such approval this month for patients with specific types of non-Hodgkin lymphoma (NHL). This decision follows the earlier approval of AbbVie and Genmab's Tepkinly (epcoritamab). Both medications are now sanctioned to treat relapsed or refractory follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) after patients have undergone at least two lines of systemic therapy. The approvals were supported by positive recommendations from the European Medicines Agency's drug advisory panel in June.

The advent of these bispecific antibodies reflects an evolving treatment landscape for NHL, with experts indicating these drugs are becoming significant in treatment protocols, especially for patients who are either not eligible for CAR-T cell therapy or relapse post-CAR-T treatment. However, some key opinion leaders (KOLs) have shown cautious optimism towards Ordspono, attributing it to its late entry into the market and its lack of distinct advantage in treating DLBCL compared to existing therapies.

AbbVie and Genmab’s drug, marketed in the U.S. as Epkinly (epcoritamab-bysp) for both FL and DLBCL, has already established a commercial presence in the region. In contrast, Regeneron's Ordspono has not yet succeeded in the U.S. market. Earlier this year, the FDA declined Ordspono’s application for accelerated approval, citing the incomplete status of confirmatory trials.

The European Commission's approval of Ordspono was bolstered by data from the Phase II ELM-2 trial and a 60-person cohort from the Phase I ELM-1 study involving DLBCL patients who had progressed after CAR-T therapy. In the Phase I trial, Ordspono exhibited an overall response rate (ORR) of 48%, with the median duration of response (DOR) being 15 months.

The pivotal ELM-2 study included two cohorts: one consisting of 128 FL patients, and another involving 127 DLBCL patients who had not undergone CAR-T therapy. In FL patients, Ordspono achieved an ORR of 80%, with 73% of these patients experiencing a complete response, and a median DOR of 25 months. The DLBCL arm showed a 52% ORR, with 31% achieving a complete response and a median DOR of 18 months.

Adverse reactions were common across both studies, with more than half of the patients experiencing cytokine release syndrome. Other frequent adverse effects included neutropenia (41%), pyrexia (39%), anemia (38%), thrombocytopenia (27%), and diarrhea (24%).

The approval of these bispecific antibodies indicates significant progress in the treatment options available for NHL, particularly for patients who have limited alternatives due to eligibility or relapse. While Ordspono faces stiff competition and has not yet penetrated the U.S. market, its approval in Europe is a crucial step in expanding treatment possibilities for NHL patients.