FDA Setbacks for Biogen and Scholar Rock in SMA Treatment Development

In a series of unexpected developments, both Biogen and Scholar Rock have encountered regulatory hurdles in their pursuit of new treatments for spinal muscular atrophy (SMA). The U.S. Food and Drug Administration (FDA) has issued complete response letters (CRLs) to both companies, citing manufacturing-related concerns.

Biogen's High-Dose Spinraza Faces FDA Scrutiny

Biogen, a leader in SMA treatment, received a CRL from the FDA regarding its application for a high-dose regimen of Spinraza (nusinersen). The agency has requested updates to "technical information" in the chemistry, manufacturing, and controls portion of the filing. Notably, the FDA did not raise concerns about the clinical data supporting the high-dose regimen.

Dr. Priya Singhal, head of development at Biogen, expressed surprise at the outcome but reaffirmed the company's commitment to bringing the high-dose regimen to SMA patients. "We are working diligently to provide the necessary information to the FDA," Singhal stated.

The proposed high-dose regimen for Spinraza involves two 50-mg starter doses given 14 days apart, followed by a 28-mg monthly maintenance dose. This represents a significant increase from the currently approved regimen, which consists of 12-mg doses administered less frequently.

Biogen's application was based on positive results from the phase 2/3 Devote trial, which demonstrated significant improvements in patient mobility as measured by the CHOP-INTED scale. The company has already secured approval for the high-dose regimen in Japan and is awaiting a decision from European regulators.

Scholar Rock's Apitegromab Faces Similar Fate

In a parallel development, Scholar Rock announced that the FDA had rejected its application for apitegromab, a monoclonal antibody candidate for SMA treatment. The rejection stemmed from issues identified during an inspection of a third-party manufacturing site in Indiana, which was not specific to apitegromab production.

The manufacturing facility in question, formerly owned by Catalent and recently acquired by Novo Nordisk, has a history of regulatory challenges. This site has been implicated in multiple FDA rejections in recent months, highlighting ongoing concerns in pharmaceutical manufacturing processes.

Industry Implications and Next Steps

These regulatory setbacks underscore the complex landscape of drug development and approval, particularly in the realm of rare diseases like SMA. While both Biogen and Scholar Rock face delays, industry analysts remain optimistic about the eventual approval of these treatments.

Biogen has stated its intention to resubmit its Spinraza application "promptly," with City analysts predicting a relatively expedited resolution to the FDA's concerns. The outcome of these resubmissions will be closely watched by patients, healthcare providers, and industry stakeholders alike, as they could significantly impact the treatment options available for SMA patients in the near future.