PUBLICATIONS

Neuromuscular 

January 21, 2026

Medication insights: onasemnogene abeparvovec-brve (Itvisma), apitegromab, nusinersen-high dose 

The U.S. Food and Drug Administration (FDA) approved onasemnogene abeparvovec-brve (Itvisma) in November 2025 for the treatment of spinal muscular atrophy (SMA) in adult and pediatric patients 2 years of age and older with confirmed mutation in the survival motor neuron 1 (SMN1) gene.¹˒² Itvisma’s active ingredient is identical to onasemnogene abeparvovec-xioi (Zolgensma) but formulated at a different concentration.² Prime Therapeutics (Prime) sought insight from key opinion leader(s) (KOLs) within our Expert Clinical Network (ECN) who specialize in neuromuscular disorders, as the approval of Itvisma will expand treatment options available to patients with SMA older than 2 years of age.² This month’s newsletter summarizes KOL feedback on this single-dose, intrathecal (IT) adeno-associated virus (AAV) vector-based gene therapy for SMA¹˒² and commentary on the recent market events within the SMA landscape, including developments for two pipeline agents for SMA, apitegromab and nusinersen-high dose (HD). 
Patient experience 

Zolgensma, which was FDA approved in May 2019, is administered as an intravenous (IV) infusion, with dosing based on patient weight, in pediatric patients under 2 years of age with SMA caused by bi-allelic mutations in the SMN1 gene.²˒³ In contrast, Itvisma is delivered as a smaller-volume formulation via a single IT injection directly into the central nervous system (CNS), independent of patient weight. With its approval, there is now the availability of a gene therapy treatment option for patients with SMA who are older than 2 years of age.² According to Prime KOLs, IT administration of Itvisma enables patients to receive a smaller dose and minimizes the side effects associated with high doses of viral vector. They note that it has yet to be determined if IT administration confers greater benefit than IV administration.  

The prescribing information for Itvisma states to consider sedation if indicated by the patient’s clinical status.¹ Prime KOLs emphasize that the decision to use sedation or anesthesia for Itvisma IT administration should be made by the treating physician but note that many of their SMA patients are able to receive nusinersen (Spinraza) intrathecally without the need for sedation or anesthesia. Furthermore, they draw attention to the fact that most centers that will administer Itvisma likely already administer Spinraza and believe that the impact on treatment logistics is likely negligible. Prime KOLs observe that aside from differences in pharmacy handling and the safeguards for the administering physician, there are no significant differences between the IT administration of Spinraza and the anticipated approach for Itvisma. 

Efficacy and safety

Given the age differences in the FDA-approved labeling and the natural, relentless progression of SMA, our KOLs indicate that Zolgensma is not a direct competitor for Itvisma. Unlike Spinraza and risdiplam (Evrysdi), Itvisma is a one-time, theoretically lifelong therapy. Prime KOLs see the potential for Itvisma to provide true stabilization of the disease, although this has not yet been proven. If its efficacy is similar to that of Spinraza and Evrysdi, Prime KOLs assert that the convenience of one-time treatment could be a decisive factor for many patients and caregivers considering a switch. Itvisma has an appealing mechanism of action and has shown a positive effect on function in clinical trials. Prime KOLs point out that given the current trial data, it is difficult to make comparisons between Itvisma and agents such as Spinraza or Evrysdi. Both Spinraza and Evrysdi showed early increases in strength and function in clinical trials; however, over time, most patients continued to decline. Our KOLs call out that Spinraza offers greater protection against functional decline as compared to Evrysdi. Whether Itvisma will prove superior to Spinraza in flattening the disease progression curve remains to be seen. 

Recent market events and pipeline 

In addition to the approval of Itvisma, there have been other notable developments within the SMA landscape. One such development pertains to apitegromab, an investigational myostatin inhibitor designed to improve motor function for patients with SMA who are already receiving Spinraza or Evrysdi. If approved, apitegromab will introduce a new mechanism of action for treating SMA. On September 23, 2025, the manufacturer, Scholar Rock, announced that the FDA issued a complete response letter (CRL) for the apitegromab Biologics License Application (BLA) for the treatment of patients with SMA. The CRL was related to observations identified during a routine general site inspection of a third-party fill-finish facility. Of note, the CRL was not specific to apitegromab, and no other approvability concerns were cited.⁴ Scholar Rock has announced it anticipates resubmitting the BLA in 2026.⁵ However, Prime KOLs comment that if approved, apitegromab will serve as an add-on agent and will likely have limited efficacy. 

Another important investigational, late-stage pipeline agent within this space is nusinersen-HD. This investigational regimen features a faster loading phase, which for treatment-naïve patients, consists of two 50 mg doses administered 14 days apart followed by a higher maintenance dose of 28 mg every 4 months compared to the approved Spinraza regimen.⁶ Biogen, the manufacturer, also announced on September 23, 2025, that a CRL was issued for the supplemental New Drug Application (sNDA) for the nusinersen-HD regimen for the treatment of SMA. The FDA requested an update to the technical information be included in the Chemistry Manufacturing and Controls (CMC) module of the sNDA. No deficiencies in the clinical data were cited.⁷ Biogen then announced in November 2025 that the nusinersen-HD regimen is currently under FDA review, with a decision expected by April 3, 2026.⁶ According to Prime KOLs, nusinersen-HD has the potential to prevent existing nusinersen patients from needing to switch to Itvisma, encouraging continued treatment with nusinersen-HD. Though less likely to occur, Prime KOLs note that patients on Evrysdi who are dissatisfied with their current treatment may also be more motivated to switch to nusinersen-HD. These innovations underscore the continued evolution of the SMA pipeline, which Prime will continue to monitor closely.

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References  
  1. Itvisma [package insert]. Bannockburn, IL; Novartis Gene Therapies; November 2025. 
  2. FDA approves gene therapy for treatment of spinal muscular atrophy. November 24, 2025. Accessed December 3, 2025. https://www.fda.gov/news-events/press-announcements/fda-approves-gene-therapy-treatment-spinal-muscular-atrophy. 
  3. Zolgensma [package insert]. Bannockburn, IL; Novartis Gene Therapies; February 2025. 
  4. FDA issues complete response letter (CRL) for apitegromab as a treatment for patients with spinal muscular atrophy (SMA) solely related to observations identified at Catalent Indiana LLC fill-finish facility. Scholar Rock, Inc. September 23, 2025. Accessed December 3, 2025. https://investors.scholarrock.com/news-releases/news-release-details/fda-issues-complete-response-letter-crl-apitegromab-treatment. 
  5. Scholar rock reports third quarter 2025 financial results and recent business highlights. Scholar Rock, Inc. November 14, 2025. Accessed December 3, 2025. https://investors.scholarrock.com/news-releases/news-release-details/scholar-rock-reports-third-quarter-2025-financial-results-and. 
  6. High dose regimen of nusinersen receives positive CHMP opinion for the treatment of spinal muscular atrophy. Biogen. November 17, 2025. Accessed December 9, 2025. https://investors.biogen.com/news-releases/news-release-details/high-dose-regimen-nusinersen-receives-positive-chmp-opinion. 
  7. Biogen provides regulatory update on high dose regimen of nusinersen. Biogen. September 23, 2025. Accessed December 3, 2025. https://investors.biogen.com/news-releases/news-release-details/biogen-provides-regulatory-update-high-dose-regimen-nusinersen.
The information contained in this report is intended for educational purposes only and is not intended to define a standard of care or exclusive course of treatment, nor be a substitute for treatment. All brand names are property of their respective owners.