FDA Approves Gene Therapy for Treatment of Spinal Muscular Atrophy

[From FDA.gov]

For Immediate Release:

November 24, 2025

The U.S. Food and Drug Administration today approved Itvisma (onasemnogene abeparvovec-brve) 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. Itvisma is an adeno-associated virus (AAV) vector-based gene therapy.

“Today’s approval shows the power of gene therapies and offers treatment to patients across the SMA disease spectrum, including patients at various ages, SMA symptoms, and motor functional levels,” said Vinay Prasad, M.D., M.P.H., the FDA’s Chief Medical and Scientific Officer and Director of the Center for Biologics Evaluation and Research. “This exciting area of science continues to change the lives of patients and the FDA is committed to expediting the development of products for unmet medical needs.”

SMA is an autosomal-recessive neurodegenerative disorder caused by mutations in the SMN1 gene, characterized by irreversible and progressive motor neuron loss, leading to progressive muscle atrophy and weakness, and subsequent paralysis and death in the most severe cases. SMA has an incidence of approximately 4-10 per 10,000 live births. Prior to the availability of effective treatment, SMA was considered one of the leading causes of infant mortality due to genetic disease in the U.S.

Itvisma demonstrated substantial evidence of effectiveness for the treatment of SMA in pediatric patients 2 years of age and older with a confirmed mutation in the SMN1 gene based on primary evidence of effectiveness from the adequate and well controlled Phase 3 study,  and the confirmatory evidence of effectiveness from data characterizing the mechanism of the product’s action, as well as efficacy findings from Zolgensma (onasemnogene abeparvovec-xioi) which contains the same active ingredient in an intravenous formulation. The applicant provided adequate justification to support expanding the indication beyond the pivotal study population to include adult patients with SMA, however, warnings and precautions are warranted due to the potentially increased risks of adverse events of special interest (e.g., hepatotoxicity and cardiotoxicity) in adult patients with preexisting chronic medical conditions.

The active ingredient (drug substance) in Itvisma is identical to Zolgensma but formulated at a different concentration. Zolgensma is administered intravenously based on patient weight to pediatric patients less than 2 years of age with SMA due to bi-allelic mutations in the SMN1 gene. Itvisma is a concentrated formulation in a smaller delivery volume, administered directly to the central nervous system via a single intrathecal injection independent of patient weight, which expands treatment options available to patients with SMA older than 2 years of age.

The direct administration of Itvisma into the cerebrospinal fluid surrounding the spinal cord (site of action) allows for delivery to motor neurons with a lower dose of vector, without the need to adjust for the patient’s body weight. This provides a treatment with rapid onset and direct targeting of the genetic root cause of SMA. By addressing the root cause of SMA, Itvisma restores SMN protein production and halts further disease progression.

The FDA review team worked collaboratively to leverage Zolgensma safety data and most of the side effects of Itvisma are consistent with identified risks associated with Zolgensma. Information from the hepatotoxicity boxed warning in the Zolgensma label is retained in the Itvisma label with appropriate modifications. This approach is supported by clinical data showing hepatotoxicity in Itvisma clinical studies.

“Significant unmet need remains in SMA, particularly for patients across various ages and motor function levels, predominantly those 2 years of age and older.” said Vijay Kumar M.D., Acting Director, Office of Therapeutic Products in the FDA’s Center for Biologics Evaluation and Research. “This approval shows our continued commitment to supporting and facilitating treatments for patients with rare diseases.”  

The FDA granted this application Fast Track, Breakthrough Therapy, and Priority Review designations. Itvisma also received Orphan Drug designation, which provides incentives to encourage the development of drugs for rare diseases. Itvisma is manufactured by Novartis Gene Therapies, Inc.

FDA Approves New Safety Warning and Revised Indication that Limits Use for Elevidys Following Reports of Fatal Liver Injury

[From FDA.gov]

For Immediate Release:

November 14, 2025

The U.S. Food and Drug Administration today announced it is taking action to approve new labeling submitted by the company that includes the addition of a Boxed Warning, the agency’s most prominent safety warning, to Elevidys (delandistrogene moxeparvovec-rokl), and that the indication section of the labeling limits the therapy’s indication to ambulatory patients four years of age and older with Duchenne muscular dystrophy (DMD). These actions follow reports of fatal acute liver failure in non-ambulatory patients treated with the product.  

Elevidys is an AAVrh74 adeno-associated virus (AAV) vector-based gene therapy approved for the treatment of DMD in certain patients. In June 2025, the FDA issued a CBER Safety Communication following two reports of fatal acute liver failure in non-ambulatory pediatric males with DMD after receiving Elevidys. In response, the manufacturer voluntarily paused distribution of Elevidys for use in non-ambulatory patients.  

In both fatal cases, patients developed markedly elevated liver enzymes and required hospitalization within two months of Elevidys infusion. An additional serious, non-fatal case of acute liver injury has involved complications such as mesenteric vein thrombosis, bowel ischemia and necrosis, and portal hypertension.  

After a comprehensive evaluation of the available safety data, FDA has now approved substantial labeling revisions for Elevidys, including:  

  • Addition of a Boxed Warning describing the risk of serious liver injury and acute liver failure, including fatal outcomes;  

  • Limiting the indication to ambulatory patients with DMD who are 4 years of age and older with a confirmed mutation in the DMD gene;  

  • Removal of the indication for non-ambulatory patients with DMD;  

  • Addition of a Limitations of Use statement to guide clinical decision-making;  

  • Updates to the Warnings and Precautions, Dosage and Administration, Adverse Reactions, Use in Specific Populations, Clinical Studies, and Patient Counseling Information sections; and  

  • Inclusion of a new Medication Guide for patients and caregivers.  

Key Safety Information for Patients and Health Care Providers  

The revised labeling includes specific safety information and monitoring recommendations:  

  • Liver monitoring: Weekly liver function tests are advised for at least three months after treatment. Patients should remain near an appropriate medical facility for at least two months post-infusion.  

  • Prompt medical attention: Patients should contact their health care provider immediately if they experience yellowing of the skin or eyes, if they miss or vomit corticosteroid doses, or if the patient experiences a change in mental status.  

  • Infection risk: Corticosteroid therapy may suppress immune function, increasing susceptibility to infections and serious complications including death.  

  • Cardiac monitoring: Weekly testing for cardiac injury (troponin-I) is advised for one month following treatment.  

  • Contraindications: Elevidys should not be used in patients with deletions involving DMD exons 8 and/or 9.   

  • Limitations of Use: Elevidys is not recommended in patients with preexisting liver impairment, recent vaccinations, or recent/active infections.  

Postmarketing Requirements  

The FDA is requiring the manufacturer to conduct a postmarketing observational study to further assess the risk of serious liver injury. The study will enroll approximately 200 patients with DMD and follow them for at least 12 months after administration of Elevidys, with periodic liver function assessments.  

Reporting Adverse Events  

Health care professionals and patients are encouraged to report adverse events, including cases of liver injury, to the FDA MedWatch program:  

Adverse events may also be reported to Sarepta Therapeutics, Inc. at 1-888-727-3782.  

The FDA remains committed to the continued evaluation of the safety and effectiveness of gene therapies and will provide updates as new information becomes available.