FDA blocks approval of Regeneron's blood cancer drug over confirmatory trial enrollment

Regeneron may have gotten ahead of itself with the early filing of bispecific antibody odronextamab to regulators. In a move that might not surprise keen FDA watchers, the agency has issued two complete response letters over the timelines of ongoing phase 3 confirmatory trials for the drug.

Regeneron submitted an approval application in September 2023 for odronextamab to treat patients with relapsed/refractory (R/R) follicular lymphoma (FL) or R/R diffuse large B-cell lymphoma (DLBCL), who have progressed after at least two prior systemic therapies. The application was supported by data from the phase 1 ELM-1 study and the phase 2 ELM-2 study.

While the application was assessed by the FDA for an anticipated accelerated approval decision on March 31, Regeneron’s plan was to continue to enroll patients in various confirmatory phase 3 lymphoma trials that formed part of the wide-ranging Olympia program. Enrollment in the dose-finding portion of these trials has already began, but the FDA decided that “the confirmatory portions of these trials should be underway and that the timelines to completion be agreed prior to resubmission” of the applications, according to Regeneron.

A critical facet of the accelerated approval process is confirmatory trials that are meant to ultimately prove that the surrogate endpoint will translate to genuine clinical benefit. FDA Commissioner Robert Califf, M.D., has successfully advocated to have those trials underway before companies get accelerated approval, with the FDA's Center for Biologics Evaluation and Research Director Peter Marks, M.D., Ph.D., telling Fierce Biotech last year that this policy was a "work in progress."

A meeting of the agency's oncologic drugs advisory committee in November 2023 also served as a reminder to cancer drug developers that the FDA is keeping a close eye on accelerated approvals.

For now, Regeneron only said that updates on the enrollment and regulatory timelines will be shared “later this year.”

Still, it could have been worse. Regeneron was keen to stress in the release that the FDA “did not identify any approvability issues” with odronextamab’s clinical efficacy, safety, trial design, labeling or manufacturing.

This is not the first regulatory setback for odronextamab, which was hit with a partial clinical hold back in 2020 over safety concerns. But since the hold was lifted in May 2021, the drug’s prospects had looked good, with the latest readout from ELM-2 in December 2023 showing objective and complete response rates of 52% and 31%, respectively.

The CD20xCD3 bispecific antibody is designed to bridge CD20 on cancer cells with CD3-expressing T cells to facilitate local T-cell activation and cancer-cell killing.