SMA Treatment Delays FAQ
Last Updated: 11/14/25
We know our community has many pressing questions related to the FDA approval delays of Scholar Rock’s apitegromab and Biogen’s high-dose Spinraza/nusinersen. This FAQ was developed to address the most common concerns and provide the latest updates as we continue to work closely with Scholar Rock, Biogen, and the FDA.
What is Cure SMA doing?
Cure SMA continues to regularly engage with and seek answers from the FDA and the companies regarding the treatment's next steps and timelines. We are also mapping out possible actions where we can have influence and impact, including elevating the urgent needs and goals of the SMA community. There has to be a formal response and resubmission from the company sponsor as a first step to address the issues raised by the regulator. While the FDA CRL decisions are final and cannot be undone or reversed, we are exploring opportunities to encourage the FDA to move swiftly to respond once the resubmissions occur. Please watch for future updates through Cure SMA. For more information on Cure SMA’s drug pipeline, please visit here.
Usually, after a CRL re-submission has been received (and accepted) by the FDA there is either a 2 month or a 6 month timeline for the FDA to decide on whether to approve. This is an area that Cure SMA will be working on now, to look for opportunities to get the FDA to work for a faster decision than the normal regulated periods.
We have recently conducted some direct advocacy initiatives with the new head of CDER at the FDA, along with several outreach efforts to legislative champions in the House and Senate. We expect to increase and broaden these efforts over the next weeks and months based on the decisions and timelines received back from the FDA on resubmissions.
Cure SMA was present and active at the Type A FDA meeting on Apitegromab to represent our community to ensure that the patient voice and the patient need were heard and factored into decisions. In particular stressing the urgency needed to address unmet needs across the entire age spectrum in SMA.
FDA History
References
August 2025
Cure SMA shares patient voice and needs with FDA
https://www.curesma.org/cure-sma-shares-patient-voice-and-needs-with-fda/
March 2025
SMA Community Risk Tolerance Update – Comparison of 2022 and 2017 SMA risk-Benefit Survey Data
https://www.curesma.org/sma-community-risk-tolerance-update-comparison-of-2022-and-2017-sma-risk-be…
https://www.curesma.org/wp-content/uploads/2025/02/SMA-Community-Risk-Tolerance-Update_02.25.pdf
July 2024
State of SMA Report (sent to FDA)
https://www.curesma.org/wp-content/uploads/2024/06/9042024_State-of-SMA_vWeb.pdf
August 2022
Cure SMA holds patient-led listening session with FDA
https://www.curesma.org/cure-sma-holds-patient-led-listening-session-with-fda/
If there are issues with the manufacturing - should those people who are on current dosage or through trials or EAP be concerned about the safety?
No, there are no current concerns with current approved product or product made for trials or EAP programs.
I would like to better understand what is meant by the reference to "unexpected manufacturing-related issues" in the context of FDA approval. My understanding is that capacity or supply chain limitations would not typically affect the FDA's decision to approve a pharmaceutical product. Should this instead be interpreted as concerns related to the quality, consistency, or sourcing of raw materials used in the manufacturing process?
This is correct that the FDA approvals are not linked to capacity items around making enough of new treatments. But they are involved in reviewing the quality and consistency of the manufacturing processes to make the new treatments. This is sometimes done in-person at the actual manufacturing sites and also with the documentation that tracks and details the specific manufacturing processes.
When will these drugs and others that are not available, finally be available to Type 1 young adults?
While the issues raised here from the FDA are not about any concerns with efficacy or safety (which is a good thing, as those would significantly slow or stop these programs), we do not have any new information yet on what the labels would be if and when they do get approved. However, we have been doing a lot of advocacy work over the last two years to reinforce the needs for approvals and labels to cover all with SMA, and especially those who are older in our community.
When is it realistic to expect approvals after this delay?
We do not know for certain, but based on past FDA actions, an approval decision on a re-submitted application could occur as soon as 3 to 5 months (under a shorter re-review process) or within 9 to 12 months (under a longer re-review process)
High Dose Spinraza from Biogen
The following responses are being provided to address your questions and are aligned with the press release which you can find here.
You can also read Biogen's full community statement to the Cure SMA community here.
What is a CRL?
A CRL is a message sent from the FDA to a company to indicate that a new drug application is not ready for approval.
What additional information has the FDA asked for?
- The FDA requested an update to the technical information included in the Chemistry Manufacturing and Controls module of our application for the new
dose regimen of nusinersen. - The FDA has identified options for resolution, and Biogen is working diligently to resubmit the application based upon readily available information.
Is there any impact on the currently approved dose?
This does not impact use or availability of the currently approved dose, which can continue to be used according to the approved product label.
Did the CRL list any concerns with the clinical data in the application?
The letter did not cite any issues with the clinical data in the application of the new dose regimen.
Does this impact ongoing clinical studies and those participating in the studies?
No. There are no changes to any ongoing clinical studies with nusinersen.
How long will it take the FDA to review the resubmission?
The high dose nusinersen (SPINRAZA) was successfully resubmitted to the FDA, with an updated PDUFA date of April 3, 2026.
Apitegromab from Scholar Rock
On September 23, 2025, Scholar Rock announced that the U.S. Food and Drug Administration (FDA) has delayed the approval with a Complete Response Letter (CRL) for the apitegromab Biologics License Application (BLA) for the treatment of people living with spinal muscular atrophy (SMA). To read Scholar Rock's initial community statement, please click here. To read Scholar Rock's updated community statement as of 10/29/25, please click here.
On November 12, 2025, Scholar Rock, alongside Cure SMA, held an in-person Type A meeting with the FDA to discuss next steps for BLA resubmission. To read Scholar Rock’s community statement on these latest BLA updates, please click here.
Below are answers from Scholar Rock addressing initial questions from the SMA community.
What was the decision by the FDA?
On September 22, Scholar Rock’s decision date, Scholar Rock received a Complete Response Letter (also known as a CRL) for the apitegromab Biologics License Application (BLA) for the treatment of patients with SMA. The CRL was solely related to observations noted by FDA during a general site inspection of a third-party vialing facility and none of the observations were specifically related to apitegromab.
What is a CRL?
A Complete Response Letter (CRL) is a decision by the U.S. Food & Drug Administration (FDA) on an application indicating that the application cannot be approved without changes. A CRL does not mean permanent rejection, and Scholar Rock is confident on a path forward for apitegromab.
Who is the manufacturer where the issues were identified?
The observations were identified at Novo Nordisk's Catalent Indiana LLC site, which is a third-party fill-finish manufacturing facility based in Bloomington, Indiana.
What is fill-finish?
This is one of the last steps in the manufacturing process (putting drug into vial).
What issues were identified at the finish-fill site?
The issues were related to Good Manufacturing Practices (GMP), which are rigorous rules that manufacturing facilities are bound to follow. These range from everything from the floor being clean to the type of safety gear that is worn. The inspection was a general site inspection and not specifically related to apitegromab.
While working with the FDA to resolve these issues, the site continues to produce commercial products for multiple other pharmaceutical companies that are administered to patients.
How is the third-party manufacturer responding?
Novo Nordisk's Catalent Indiana site has been extremely collaborative with Scholar Rock and the FDA. They have provided a comprehensive response to the FDA’s observations, which was submitted in early August, and they are working rapidly on the remediation activities.
On November 12, 2025, Catalent Indiana, LLC (part of Novo Nordisk), joined Scholar Rock, alongside Cure SMA, at the meeting and presented the progress in executing the remediation plan at the site and affirmed that it expects the facility to be ready for reinspection by the end of this year.
What are Scholar Rock’s next steps with the FDA?
- As mentioned, Scholar Rock held the Type A meeting with the FDA in-person alongside Cure SMA. The meeting reinforced that there are no other approvability concerns, including apitegromab’s efficacy and safety data. It remains clear that the CRL they received from FDA in September is based solely on Novo Nordisk’s Bloomington, Indiana site.
- Scholar Rock remains in close coordination with Novo Nordisk as it awaits meeting minutes from the FDA. After completion of necessary reviews by the FDA, communications with Novo Nordisk, and a successful site reinspection of their Bloomington, Indiana facility, Scholar Rock anticipates resubmission of the BLA and U.S. launch of apitegromab, pending FDA approval, in 2026.
What is a Type A meeting with the FDA?
A Type A meeting is a high-priority meeting between the FDA and a new drug applicant intended to resolve issues for regulatory approval. Of the meeting types that can follow a CRL, Type A meetings are treated with the strongest sense of urgency.
What was the outcome of the Type A meeting?
- The Type A meeting with FDA was constructive and collaborative. Coming out of the meeting, there is a shared understanding of the high unmet need for the SMA community and a sense of urgency to bring apitegromab to children and adults living with SMA.
- As mentioned, Novo Nordisk affirmed that the facility is on track to be ready for reinspection by the end of this year, and the meeting reinforced that there are no other approvability concerns, including apitegromab’s efficacy and safety data.
Why is Scholar Rock onboarding a new fill-finish facility? Does this mean the company doesn’t have confidence in the Novo Nordisk facility being fixed?
- During the Type A meeting, Novo Nordisk affirmed that its Bloomington, Indiana facility is on track to be ready for reinspection by the end of this year.
- While Scholar Rock had always planned to onboard a second fill-finish facility, they have now accelerated the process to bring a second facility online for apitegromab.
- Scholar Rock will continue to work closely with Novo Nordisk moving forward.
How long will it take to get up and running at a new fill-finish facility?
The process of technology transfer is underway, and commercial capacity has been reserved beginning in the first quarter of 2026. Technology transfer, often referred to as “tech transfer,” is the process of transferring knowledge, skills, and expertise from one facility to another.
When is it realistic to expect approvals after this delay?
Scholar Rock anticipates resubmission of the BLA and U.S. launch, pending FDA approval, for apitegromab in 2026.
Is the apitegromab drug supply utilized in the Scholar Rock clinical trials and Expanded Access Program (EAP) safe?
- Yes, it is safe.
- All apitegromab used, whether for clinical trials, early access program, or already manufactured commercial product, must clear numerous quality evaluations before being released for use.
- To date, apitegromab has been administered in more than 400 children and adults across all apitegromab clinical studies with over 700 patient years of experience in SMA alone.
- There are clinical trial patients who have been treated with apitegromab for over six consecutive years to date.
Is the product in the Expanded Access Program (EAP) manufactured at this site?
Apitegromab active pharmaceutical ingredient is not manufactured at this site. However, Novo Nordisk’s Catalent Indiana site is the site where apitegromab is put into the vial.
Will there be any impact on Scholar Rock Expanded Access Program (EAP) or trial participants?
No, there will be no impacts to currently enrolled EAP participants and clinical trial patients. All participants currently enrolled in the EAP or a clinical trial sponsored by Scholar Rock will continue to receive high quality apitegromab without interruption. The company received significant interest in its EAP and closed enrollment as of the company’s September PDUFA date. Scholar Rock is unable to reopen enrollment to its EAP at this time, as it works to bring apitegromab to as many SMA patients as possible.
Should people who are on either dosage through trials be concerned about the safety?
No, there is not a quality issue with either dose.
If Scholar Rock continues EAP, will they think about expanding the locations that have access to that program?
- The EAP continues for currently enrolled patients.
- The EAP was closed to new participants in anticipation of the decision date announcement. Scholar Rock is working to understand the impact of the CRL on apitegromab’s timelines for potential approval.
- The company remains hopeful the approval process will be expeditious.
My understanding is that capacity or supply chain limitations would not typically affect the FDA's decision to approve a pharmaceutical product. Should this instead be interpreted as concerns related to the quality, consistency, or sourcing of raw materials used in the manufacturing process?
- No, this is not related to the quality, consistency, or sourcing of raw materials for apitegromab.
- A typical FDA approval includes inspections not only of manufacturing but also of supply chain, trial sites, etc.
- At Scholar Rock, the company has a robust supply of commercial vials prepared which will be available upon FDA approval.
It is my understanding that this medication has been delayed several times without any formal announcement. It feels like there is a larger issue here.
There have been no previous delays up until this CRL for apitegromab.
What does the classification of Official Action Indicated (OAI) mean?
The inspection that led to Scholar Rock’s CRL is classified as Official Action Indicated (OAI). OAI classification typically means that FDA will require a satisfactory follow-up inspection of the facility before allowing any applications for new medicines manufactured at the facility to be approved for commercial use.
What does this mean for how quickly Scholar Rock can resubmit the BLA?
Scholar Rock anticipates resubmission of the BLA and U.S. launch, pending FDA approval, for apitegromab in 2026.
If the site is “not in a state of compliance,” is manufacturing still allowed?
Official Action Indicated (OAI) means that a site must make corrective actions, but it does not suspend manufacturing. The fill-finish process of apitegromab continues today under robust processes to ensure the quality and safety of current and ongoing apitegromab supply. Commercially approved medicines can continue to be vialed at the site and administered to patients.
What does Official Action Indicated (OAI) mean for product supply?
Scholar Rock does not expect disruptions to their current and ongoing apitegromab supply. Scholar Rock has adequate inventory and will continue robust oversight while the third-party manufacturing site addresses the FDA's observations.
What does Official Action Indicated (OAI) mean for product safety?
OAI is not related to apitegromab. Based on numerous reviews to date, there are no impacts to the quality or safety of the current and ongoing apitegromab supply.
Has Scholar Rock put extra controls in place to ensure product quality and safety?
Scholar Rock has robust processes to ensure all apitegromab product for EAP and clinical trials meets quality and safety standards.
Definitions:
Class 2 Resubmission review: The FDA’s standard six-month review timeline for a resubmission.
Class 1 Resubmission review: The FDA’s standard three-month review timeline for a resubmission
Complete Response Letter - CRL: The FDA’s way of saying “revise and resubmit” – aspects of the application need to be updated before FDA can complete its review and make a decision. The details of a CRL vary across drug applications. Receiving a CRL means that the review of the BLA or NDA has stopped and the FDA review will only continue when changes have been made and resubmitted. Once a BLA or NDA is resubmitted, a new review cycle starts.
CMC (Chemistry, Manufacturing, and Controls): What does CMC mean? In drug development, chemistry relates to the drug substance itself – its molecular structure, purity and stability. Manufacturing covers all the processes involved in producing the drug, from synthesizing the active ingredients to formulating the final product. Controls are the procedures put in place to guarantee that the drug consistently meets predefined quality standards throughout its entire lifecycle including determining its shelf life and storage conditions.