The phase 1 ASCEND trial is testing a single intrathecal dose of the investigational AAV9 gene therapy INS1201 in young boys with Duchenne muscular dystrophy.
Insmed is enrolling ambulatory boys with Duchenne muscular dystrophy (DMD) in a phase 1 trial (NCT06817382) testing INS1201, an investigational AAV9-based micro-dystrophin gene therapy delivered as a single intrathecal injection into the cerebrospinal fluid (CSF) rather than through the intravenous infusion used by delandistrogene moxeparvovec (Elevidys; Sarepta), the only currently approved DMD gene therapy.1
Investigators presented the design of the trial, known as ASCEND, at the
ASCEND is a phase 1, open-label, multicenter, dose-escalation study evaluating up to 12 ambulatory boys with DMD, divided into 2 parts by age: Part 1 enrolls boys ages 3 to younger than 5 years, and Part 2 enrolls boys ages 2 to younger than 3 years. Each part includes 2 sequential dose cohorts of 3 participants each, receiving a single intrathecal dose of either 5.0x1014 or 1.0x1015 vector genomes of INS1201. All participants must carry a qualifying DMD variant within exons 18 through 58.1,2
Enrollment is staggered, with a 30-day safety observation period between each participant, and an independent data monitoring committee convenes after the last participant's observation period in each of the first 3 cohorts before the next cohort opens. The primary endpoint is the incidence and severity of treatment-emergent adverse events (AEs), AEs of special interest, and serious AEs.
Secondary endpoints include identification of a recommended phase 2 dose and change from baseline in muscle micro-dystrophin DNA and expression; exploratory endpoints include biodistribution and functional and caregiver-reported outcomes. Participants are followed for 96 weeks post-administration, followed by a 3-year safety extension study. As of June 2026, the trial was actively enrolling at 10 sites in the United States.
Elevidys,
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INS1201 instead uses an AAV9 capsid given as a single intrathecal injection into the CSF. In preclinical studies in mice and nonhuman primates scheduled for presentation at the 2027 MDA Clinical & Scientific Conference, Insmed researchers reported that CSF-delivered vector reached muscle groups throughout the body, including cardiac muscle, with limited distribution to the liver compared with systemic dosing. Good laboratory practice toxicology studies in both species over 3 months found the therapy well tolerated at all doses tested, with the no-observed-adverse-effect level reaching the highest dose tested in each study.4
Both therapies exclude patients with pre-existing immunity to their respective AAV capsid; ASCEND requires a total serum anti-AAV9 antibody titer no greater than 1:50 within 14 days of dosing, and also excludes boys with prior gene or cell-based therapy, recent exon-skipping or stop-codon readthrough treatment, or reduced cardiac function on screening echocardiogram.2
The FDA cleared Insmed's investigational new drug application for INS1201 in December 2024, the company's first gene therapy candidate to reach the clinic. Insmed has said it plans roughly 1 to 2 such filings per year from its gene therapy research platform, which also includes earlier-stage programs for amyotrophic lateral sclerosis (INS1202) and Stargardt disease (INS1203).3
With dose escalation ongoing across its 4 cohorts, ASCEND's independent data monitoring committee will continue to review safety data before each successive cohort begins dosing. Secondary and exploratory endpoints, including muscle dystrophin expression and functional outcomes, will be assessed through the 96-week primary follow-up period, with safety tracked for an additional 3 years.1,2
