The regulatory action marks the second rejection for a spinal muscular atrophy therapy this week after Scholar Rock’s apitegromab was issued a complete response letter on Tuesday, similarly on manufacturing grounds.
The FDA has denied approval for a higher-dose formulation of Biogen’s antisense oligonucleotide Spinraza, marking the second time in the same day that manufacturing issues led to the rejection of a medicine for spinal muscular atrophy.
BMO Capital Markets labeled the rejection as a surprise, with just a technicality holding back the approval.
Biogen’s news release on Tuesday was thin on details, with the company noting only that the regulator is asking for updated technical information in the chemistry manufacturing and controls portion of the application. The FDA did not identify problems with Biogen’s clinical data package for high-dose Spinraza. Biogen is working to address the agency’s requests and plans to refile the application “promptly,” according to the announcement.
“Given the limited scope of updates required and lack of efficacy concerns raised, we see no true concerns to high-dose nusinersen’s ultimate approval,” BMO Capital Markets told investors in a Tuesday note, adding that the FDA’s issues pose a “quickly resolvable setback” for Biogen. Still, given that investors were not anticipating a delay, the rejection could result in a “minor downside” to the company’s shares.
Shares of Biogen were steady at $138.41 in pre-market trading Wednesday.
Spinraza’s rejection was the second regulatory defeat for the spinal muscular atrophy space on Tuesday. Earlier in the day, the FDA also handed a complete response letter to Scholar Rock’s myostatin inhibitor apitegromab—likewise over manufacturing concerns. In particular, the regulator pointed to certain issues at a third-party fill-finish site managed by Novo Nordisk. Among the observations, outlined in a report made public last month, were persistent bacterial contamination and pest infestations.
Spinraza, which contains the active ingredient nusinersen, works by promoting the production of the SMN protein, which is typically deficient in patients with spinal muscular atrophy. The drug was approved in 2016 for this condition, though its current regimen involves a 12-mg dose with an induction schedule involving four loading doses. Biogen’s proposed higher-dose formulation uses two 50-mg intrathecal injections for initiation, followed by 28-mg maintenance doses.
Biogen backed its higher-dose application with data from the Phase II/III DEVOTE study, which showed that the investigational formulation of Spinraza elicited significantly higher improvements in motor skills as compared with a sham control. Higher-dose Spinraza also outperformed the standard-dose formulation in terms of motor function, though the effect fell short of significance.
