FDA approval of Regeneron’s myeloma drug delayed due to manufacturing issues

Regeneron submitted​ linvoseltamab, a bispecific antibody treatment for relapsed/refractory multiple myeloma, for FDA priority review in February this year.

The drug works to destroy cancer cells by binding to both a cancer protein, BCMA, and the CD3 receptor on a patient’s T cells. The antibody has been tested in a phase 1/2 trial and after a median of 14 months follow-up the objective and complete response rates to the therapy were 71% and 50%, respectively.

The FDA issued​ a Complete Response Letter to the biologics licensing application this week stating that the decision on approval of the therapy has been delayed due to “findings from a pre-approval inspection at a third-party fill/finish manufacturer for another company’s product candidate.” The company in question is also involved with manufacturing and preparing linvoseltamab for patient use.

The third-party company was not named by Regeneron, but the US-based pharma company said in a press statement that it believes the issues found during the FDA inspection have “been resolved” and that the facility involved is waiting a new inspection by the regulator that it expects to happen soon.

The announcement was not unexpected, as Regeneron had already mentioned in a call about second quarter 2024 earnings that the regulator had warned the company of a possible delay in approval of linvoseltamab.

“While we now believe these findings have been resolved, a reinspection will be required and therefore, we anticipate any potential FDA approval for linvoseltamab is likely to be delayed beyond the August 22 PDUFA date,” said Leonard Schleifer, Regeneron Pharmaceuticals CEO, during the earlier call​.

“The FDA has not informed us of any approvability issues for linvoseltamab related to safety, efficacy, or the status of our ongoing confirmatory trial.”

The antibody is currently under review for the same indication by the European Medicines Agency.

Matching up to the competition ​

Multiple myeloma is the second most common blood cancer and has a 5-year survival rate of around 54% in the US. It is treatable, but many people relapse after initial therapy.

If it achieves approval, linvoseltamab will have to compete with both Pfizer and Johnson & Johnson’s bispecific antibody treatments for multiple myeloma.

Other recent treatments for the blood cancer include chimeric antigen receptor (CAR) T-cell therapy, which can be very effective but can also be expensive and time consuming to produce and can cause serious adverse events.

J&J’s teclistamab (sold as Tecvayli) is also a BCMA/CD3 antibody and won accelerated FDA approval in 2022. Pfizer’s elranatamab (sold as Elrexfio) also targets the same two receptors and was given accelerated approval by the FDA last year. Both these therapies are only approved as fifth line therapies.

Regeneron has applied for approval of linvoseltamab as a third-line therapy, which could give it an edge over its bispecific competitors. Results also suggest that linvoseltamab might be slightly more effective and have a better side effect profile than that of competitors, although side effects such as cytokine release syndrome seem to be common with all the bispecific antibody therapies. It is also difficult to make any true comparisons with other antibodies without direct head-to-head trial results.