FDA Issues Complete Response Letter for Apitegromab in Spinal Muscular Atrophy

The Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) to Scholar Rock regarding the Biologics License Application (BLA) for apitegromab for the treatment of spinal muscular atrophy (SMA). 

Apitegromab, a fully human monoclonal antibody, works by selectively binding to the pro- and latent forms of myostatin in order to inhibit myostatin activation. This binding is expected to improve motor function in SMA patients.

The CRL was related to observations, not specific to apitegromab, reported during a routine site inspection of Catalent Indiana, a third-party fill-finish facility. The letter did not mention any concerns regarding apitegromab’s efficacy or safety, or the third-party drug substance manufacturer. 

To address the issues, Catalent Indiana submitted a detailed response in early August 2025. According to Scholar Rock, the resubmission of the BLA for apitegromab will be initiated once the manufacturing issues get resolved. 

The BLA submission included data from the phase 3 SAPPHIRE trial (ClinicalTrials.gov Identifier: NCT05156320) as well as supportive data from the phase 2 TOPAZ trial (ClinicalTrials.gov Identifier: NCT03921528) and the long-term extension ONYX trial (ClinicalTrials.gov Identifier: NCT05626855). 

Findings from the pivotal SAPPHIRE trial showed that patients treated with apitegromab saw a statistically significant and clinically meaningful improvement in motor function compared with placebo (P =.0192). These improvements were also seen in the pooled population across various subgroups and geographic regions. 

Commenting on the letter, David L. Halal, Chairman and Chief Executive Officer of Scholar Rock said, “We are continuing to work closely with Catalent Indiana on the FDA’s manufacturing observations so that we can resubmit the apitegromab BLA as soon as possible. We remain focused on working hand-in-hand with the FDA to pursue approval of the first and only muscle-targeted treatment for people living with SMA.”

This article originally appeared on MPR