FDA Rejects Two Spinal Muscular Atrophy Therapies Over Manufacturing Concerns

In a surprising turn of events, the U.S. Food and Drug Administration (FDA) has denied approval for two spinal muscular atrophy (SMA) therapies on the same day, citing manufacturing issues in both cases. The rejections have sent ripples through the pharmaceutical industry, highlighting the critical importance of manufacturing processes in drug development and approval.

Biogen's High-Dose Spinraza Faces Setback

Biogen, a leading player in the SMA treatment landscape, received an unexpected rejection from the FDA for its higher-dose formulation of Spinraza (nusinersen). The regulatory agency is requesting updated technical information in the chemistry manufacturing and controls (CMC) portion of the application. Importantly, the FDA did not identify any problems with Biogen's clinical data package for the high-dose version of the drug.

Spinraza, which contains the active ingredient nusinersen, works by promoting the production of the SMN protein, typically deficient in SMA patients. The current approved regimen involves a 12-mg dose with an induction schedule of four loading doses. Biogen's proposed higher-dose formulation aims to simplify the treatment process with two 50-mg intrathecal injections for initiation, followed by 28-mg maintenance doses.

The company supported its application with data from the Phase II/III DEVOTE study, which demonstrated that the investigational formulation of Spinraza elicited significantly higher improvements in motor skills compared to a sham control. The higher-dose formulation also showed improved motor function over the standard dose, although this effect did not reach statistical significance.

Biogen has stated that it is working to address the FDA's requests and plans to refile the application "promptly." Despite the setback, BMO Capital Markets analysts remain optimistic, describing the issue as a "quickly resolvable setback" and predicting no significant obstacles to the ultimate approval of high-dose nusinersen.

Scholar Rock's Apitegromab Also Faces Rejection

In a parallel development, Scholar Rock received a complete response letter from the FDA for its myostatin inhibitor, apitegromab, also intended for SMA treatment. The rejection similarly stemmed from manufacturing concerns, specifically issues at a third-party fill-finish site managed by Novo Nordisk.

The FDA's observations, detailed in a report made public last month, included persistent bacterial contamination and pest infestations at the manufacturing facility. These issues underscore the stringent quality control measures required in pharmaceutical production and the potential consequences of relying on third-party manufacturers.

The dual rejections in the SMA space on a single day highlight the complex landscape of drug development and approval, where clinical efficacy alone is not sufficient to secure regulatory green lights. As both Biogen and Scholar Rock work to address these manufacturing-related concerns, the SMA patient community and investors alike will be closely watching for updates on the path forward for these potentially groundbreaking therapies.