Regeneron to conduct confirmatory trials for odronextamab for FDA approval

With Regeneron’s desire to move its blood cancer medicine odronextamab from fifth line to first in some instances as treatment, the Food and Drug Administration (FDA) has now issued a complete response letter (CRL) to the company demanding that the current enrollment status of the confirmatory trials needs to be worked on.

Unless the aforementioned issues are fixed the agency has refused to approve the drug under the accelerated review pathway. When a submission was initially made to the agency it was supplemented by the phase 1 ELM-1 study and the phase 2 ELM-2 study.

In order to support the approval for the bispecific antibody in R/R diffuse large B-cell lymphoma and relapsed/refractory (R/R) follicular lymphoma the company is currently running 5 trials.

Andres Sirulnik who serves as the senior vice president, of translational and clinical sciences for hematology has downplayed these concerns by claiming that enrollment is coming along just fine and that the company is on teh cusp of satisfying the demands made by the FDA.

While randomization in trials hasn’t begun yet by the time Regeneron files for accelerated approval these matters will be dealt with.

Sirulnik was quick to clarify though that no concerns were raised by the regulatory agency when it came to the safety or efficacy of the drug, the only point of contention has been on the technical aspect of the trials.

Since the company wanted to move the treatment up in line the agency wanted a safety lead-in test to be conducted prior to the randomization process. Before proceeding any further, safety was a big priority for the FDA, therefore for each of the studies and indications mentioned, they wanted to see a small group of patients, Sirulnik explained. According to him, the only thing holding them back is that all the patients are in the safety lead-in in all these studies, as soon as the safety lead-in is clear, the company can begin the randomization phase.

The FDA’s emphasis on confirmatory trials is a new thing, in the past when based on a surrogate endpoint for conditions with an unmet need, certain drugs were approved on accelerated grounds. It was later these copies who had to conduct confirmatory trials to gain full approval.

Now though, the agency has tightened the nose around everyone’s neck and all companies are expected to have the studies “well underway” at the time of filing. This, however, has proved to be an issue since the definition of well underway has not been clarified by the agency.

While Regeneron has not announced when it will be submitting its application for the approval of odronextamab, representatives of the company are still hopeful that once back in the hands of the agency it will be reviewed under the accelerated pathway.