Sarepta and Hansa End Partnership, Halting AAV Gene Therapy Trial for Antibody-Positive DMD Patients

BOSTON, MA – November 21, 2025- Sarepta Therapeutics has terminated a Phase I clinical trial, a setback in efforts to expand the patient pool eligible for its Duchenne Muscular Dystrophy (DMD) AAV gene therapy, Elevidys (delandistrogene moxeparvovec). The study, which was evaluating a combination with Hansa Biosciences’ Idefirix (imlifidase), was stopped due to a “business decision,” according to the ClinicalTrials.gov listing (NCT06241950).

The trial’s goal was to explore whether pre-treatment with Idefirix—an antibody-cleaving enzyme—could reduce pre-existing IgG antibodies against the AAV vector, allowing patients otherwise ineligible for the one-time AAV gene therapy to receive Elevidys.

The inability to re-dose or treat patients with pre-existing antibodies remains a significant challenge for the entire AAV gene therapy field. Elevidys, which utilizes the AAVrh74 serotype to deliver a micro-dystrophin gene, requires patients to have low or undetectable levels of anti-AAV antibodies to ensure the viral vector successfully transduces muscle cells.

Hansa had presented promising data in August 2025 from three patients in the trial, demonstrating that treatment with Idefirix led to a rapid reduction of IgG antibodies to levels $\geq$95% less than baseline. This “clearing” mechanism would typically open the door for AAV dosing.

However, despite successful AAV-mediated transduction and micro-dystrophin expression at 12 weeks post-Elevidys treatment in these pre-treated patients, the expression levels were reported as lower compared to other patient populations at the same time point. This potential signal of sub-optimal efficacy, alongside broader business considerations, may have factored into Sarepta’s decision.

The termination voids the 2020 agreement between the two companies. Hansa had received an upfront payment of $\$10$ million and was eligible for substantial development, regulatory, and sales milestones potentially totaling up to $\$397.5$ million. Hansa would have retained all Idefirix sales and tiered royalties up to the mid-teens on incremental AAV gene therapy sales resulting from treating antibody-positive patients enabled by the pre-treatment.

This partnership termination is the latest in a series of setbacks for Sarepta’s AAV portfolio in 2025.

• Elevidys Safety and Labeling: The US Food and Drug Administration (FDA) has placed multiple pauses on the company’s trials involving the DMD AAV therapy. Most notably, the agency temporarily halted sales and added a black box label to Elevidys following the deaths of two patients attributed to acute liver failure. The label has since been restricted to ambulatory patients.

• Pipeline Cuts: Sarepta has also culled other pipeline candidates after a 51-year-old man with limb-girdle muscular dystrophy (LGMD) type 2D/R3 died following treatment with the investigational AAV gene therapy candidate SRP-9004 in a Phase I trial, another event that led to an FDA hold on the company’s LGMD AAV trials.

• Efficacy Miss: Separately, a pivotal trial of two of its exon-skipping drugs, AMONDYS 45 (casimersen) and VYONDYS 53 (golodirsen), failed to show a statistical benefit compared to placebo in the primary endpoint. Sarepta, however, plans to meet with the FDA to discuss converting their accelerated approval to traditional approval based on numerical trends favoring treatment and a favorable safety profile.

The termination of the Idefirix collaboration underscores the current turbulence surrounding Sarepta’s AAV gene therapy platform as the company navigates significant regulatory and clinical challenges across its entire pipeline.