FDA Rejects Two Spinal Muscular Atrophy Therapies, Citing Manufacturing Concerns

The U.S. Food and Drug Administration (FDA) has dealt a double blow to the spinal muscular atrophy (SMA) treatment landscape, rejecting two therapies on the same day due to manufacturing issues. Biogen's high-dose formulation of Spinraza and Scholar Rock's apitegromab both received complete response letters from the regulatory agency, highlighting the importance of robust manufacturing processes in drug development.

Biogen's Spinraza Setback

Biogen faced an unexpected hurdle in its efforts to expand the treatment options for SMA patients when the FDA denied approval for a higher-dose formulation of Spinraza (nusinersen). The company reported that the rejection was based on the need for updated technical information in the chemistry manufacturing and controls (CMC) portion of the application. Importantly, the FDA did not raise concerns about the clinical data package for high-dose Spinraza.

The proposed higher-dose formulation aimed to simplify the treatment regimen, offering two 50-mg intrathecal injections for initiation, followed by 28-mg maintenance doses. This contrasts with the current approved regimen of 12-mg doses with four loading doses. Biogen supported its application with data from the Phase II/III DEVOTE study, which demonstrated significantly higher improvements in motor skills compared to a sham control.

Despite the setback, BMO Capital Markets analysts view this as a "quickly resolvable" issue, predicting no significant obstacles to the ultimate approval of high-dose nusinersen. Biogen has stated its intention to address the FDA's requests promptly and refile the application.

Scholar Rock's Apitegromab Faces Similar Fate

In a parallel development, Scholar Rock received a complete response letter for its myostatin inhibitor apitegromab, also targeting SMA treatment. The FDA's concerns centered on manufacturing issues at a third-party fill-finish site managed by Novo Nordisk. A public report released last month highlighted persistent bacterial contamination and pest infestations at the facility.

Impact on the SMA Treatment Landscape

These regulatory actions underscore the FDA's stringent requirements for manufacturing processes, even when clinical data appears promising. The rejections may temporarily limit new treatment options for SMA patients, a rare genetic disorder characterized by muscle weakness and atrophy.

Spinraza, first approved in 2016, has been a cornerstone of SMA treatment, working by promoting the production of the SMN protein, which is typically deficient in SMA patients. The higher-dose formulation aimed to build on this success, potentially offering improved efficacy and a more convenient dosing schedule.

As both Biogen and Scholar Rock work to address the FDA's concerns, the SMA community awaits updates on the timeline for potential resubmissions and approvals. These developments highlight the complex interplay between drug efficacy, safety, and manufacturing quality in the pharmaceutical industry's pursuit of innovative therapies for rare diseases.