FDA refuses to approve Regeneron’s blood cancer medication

Regeneron’s hasty submission of the bispecific antibody odronextamab to regulatory authorities suggests they may have acted prematurely. This move, not unexpected by astute observers of the FDA, has resulted in the agency issuing two complete response letters regarding the timelines for ongoing phase 3 confirmatory trials of the drug.
In September 2023, Regeneron applied for approval of odronextamab to treat patients with relapsed/refractory follicular lymphoma (FL) or diffuse large B-cell lymphoma (DLBCL) who had undergone at least two prior systemic therapies. This application relied on data from the phase 1 ELM-1 study and the phase 2 ELM-2 study.

While awaiting an accelerated approval decision by March 31, Regeneron’s strategy included continuing patient enrollment in various confirmatory phase 3 lymphoma trials under the Olympia program. Although enrollment for the dose-finding segment of these trials had commenced, the FDA insisted that the confirmatory portions be in progress with agreed-upon completion timelines before the applications could be resubmitted.
A crucial aspect of the accelerated approval process involves confirmatory trials aimed at demonstrating that surrogate endpoints indeed lead to tangible clinical benefits. FDA Commissioner Robert Califf has been a proponent of having these trials underway before granting accelerated approvals, a sentiment echoed by FDA’s Center for Biologics Evaluation and Research Director Peter Marks, who referred to this policy as a work in progress.

The oncologic drugs advisory committee meeting in November 2023 served as a reminder to cancer drug developers of the FDA’s vigilant oversight of accelerated approvals.
Regeneron has stated that updates regarding enrollment and regulatory timelines will be provided “later this year.” Despite the setback, the company highlighted that the FDA did not raise any concerns regarding odronextamab’s clinical efficacy, safety, trial design, labeling, or manufacturing.
This is not the first time odronextamab has faced regulatory challenges; it previously encountered a partial clinical hold in 2020 due to safety concerns, which was lifted in May 2021. Subsequently, the drug showed promising outcomes, with the latest data from ELM-2 in December 2023 revealing objective and complete response rates of 52% and 31%, respectively.
The CD20xCD3 bispecific antibody’s mechanism of action involves bridging CD20 on cancer cells with CD3-expressing T cells, aiming to activate local T-cell responses and induce cancer cell death.