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The FDA has rejected Scholar Rock's application for approval of spinal muscular atrophy treatment apitegromab, citing issues with a third-party manufacturing site now owned by Novo Nordisk. Scholar Rock’s bid to become the first company to win FDA approval for a muscle-targeted treatment for spinal muscular atrophy (SMA) has been tripped up by a manufacturing issue.The FDA sent a complete response letter (CRL) to the Massachusetts biotech, rejecting its application for approval of apitegromab. The U.S. regulator cited observations stemming from a general site inspection of a third-party contract manufacturing facility in Indiana, which Novo Nordisk acquired from Catalent as part of its parent company's acquisition of the CDMO last year.The issues that were identified were not specific to the production of apitegromab, Scholar Rock said, adding that the CRL did not cite any FDA concerns relating to the efficacy or safety of the drug, which is an infused monoclonal antibody treatment. During its second quarter earnings presentation last month, Scholar Rock warned investors of the likelihood of an FDA rejection, citing issues at two third-party contract manufacturers, including one that was unnamed and performs drug substance manufacturing of apitegromab. On Tuesday, Scholar Rock said that the CRL did not identify any problems with that portion of apitegromab’s production.In early August, the facility, which Scholar Rock referred to as Catalent Indiana, submitted a response seeking to address the FDA's concerns. Following that submission, the site has continued to take corrective action and update the FDA accordingly, Scholar Rock said. When the issues are resolved, Scholar Rock will resubmit its Biologics License Application (BLA), with the expectation that the U.S. regulator will “act expeditiously,” the company said. The original target date for the FDA decision was Monday. “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,” David Hallal, Scholar Rock’s chairman and CEO, said in a release.Problems with Novo Nordisk’s large-scale fill-finish facility, which is in Bloomington, Indiana, are nothing new. In 2023, an FDA decision on Regeneron’s high-dose version of Eylea was delayed for two months because of issues at the plant.Last month, during its second quarter presentation, Regeneron said that two more FDA decisions relating to Eylea were being held up because of problems uncovered at the Bloomington facility in a July inspection. The company also cited the issues as the reason for an FDA rejection of its blood cancer bispecific odronextamab.In a $16.5 billion deal that was completed in December of last year, Novo Nordisk's parent Novo Holdings bought out Catalent. The transaction included Novo Holdings’ sale of three Catalent plants—one of them the Bloomington site—to Novo Nordisk for $11 billion.As for Scholar Rock, the delay affects an asset that it hopes to convert into its first marketed product. The 13-year-old company reported a cash balance of $295 million as of June 30, with its runway extending into 2027.Regulators in Europe also are reviewing an application for approval of apitegromab, with Scholar Rock expecting to launch there in 2026. Jefferies analyst Amy Li projects peak sales for the anti-myostatin drug to reach $1.8 billion.Because of its ability to preserve muscle loss, apitegromab is seen as a potential treatment to pair with obesity drugs. In June, Scholar Rock presented results from a phase 2 proof-of-concept study that showed that combining apitegromab with Eli Lilly’s tirzepatide provided a 15% loss of muscle compared to a 30% loss for patients using tirzepatide and placebo after 24 weeks. Apitegromab has been shown to improve motor function in SMA patients who are also receiving treatments that prevent motor neuron loss associated with the disease but do not directly address muscle deterioration. These medicines, all blockbusters, include Novartis’ Zolgensma, Biogen’s Spinraza and Roche’s Evrysdi.“Muscle strength and motor function are significant unmet needs for many in the SMA community and are fundamental to independence,” Kenneth Hobby, President of Cure SMA, said in the release. “A gain in motor function can allow someone to participate in important activities of daily living from self-care to work and social interactions, and as such, we urgently await the availability of the first-ever treatment with the potential to address the muscular component of SMA.”