Phase 1/2 trial of del-brax enrolling new, possibly pivotal FSHD group
Intent is to collect biomarker data that could support FDA accelerated approval
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A new patient group is being enrolled in a Phase 1/2 trial of delpacibart braxlosiran (del-brax), an experimental and potentially disease-modifying therapy for facioscapulohumeral muscular dystrophy (FSHD), its developer, Avidity Biosciences, announced.
The additional trial cohort, which is expected to be recruited in full early next year, aims to evaluate the effects of del-brax on disease biomarkers of FSHD. Assuming results are positive, Avidity is planning to use trial results as a basis to apply for accelerated approval of del-brax.
“The initiation of the biomarker cohort marks a key step in our strategy to pursue a potential accelerated approval path for del-brax, the first potential treatment to directly target the root cause of FSHD,” Steve Hughes, MD, Avidity’s chief medical officer, said in a company press release.
FORTITUDE clinical trial is enrolling at sites in Canada, US, and UK
Accelerated approval is a pathway allowing the U.S. Food and Drug Administration (FDA) to conditionally approve a therapy based on early biological data suggesting the treatment can benefit patients. When therapies are granted accelerated approval, developers are required to conduct additional studies to prove the treatment actually does offer clinical benefits. Since trials to establish such benefit usually take much longer than biomarker studies, this pathway allows the FDA to make promising new medicines available more quickly to patients.
New group enrollment in the Phase 1/2 FORTITUDE clinical trial (NCT05747924) is open to people with FSHD ages 16 through 70. Recruitment of about 40 patients is ongoing at several locations across the U.S., U.K., and Canada.
“We are advancing our clinical studies for del-brax as quickly as possible as we understand the urgency to bring a potential new treatment to people living with FSHD who have no treatment options,” Hughes said.
FSHD is caused by a mutation that leads to production of the protein DUX4 in cells where this protein normally is not produced. This is believed to be toxic to cells and to ultimately drive disease symptoms.
Del-brax aims to lower DUX4 levels by targeting the protein’s production
Del-brax, previously known as AOC 1020, is designed to reduce production of the DUX4 protein by targeting its messenger RNA, an intermediary molecule that’s used when the DUX4 gene is “read” to make the protein. The therapy contains an antibody that binds to the transferrin receptor 1 in muscle cells, along with a small interfering RNA to reduce DUX4 messenger RNA.
FORTITUDE’s biomarker cohort essentially will help scientists assess del-brax’s effects on DUX4-regulated biomarkers. The trial’s primary goals are to evaluate alterations in the levels of DUX4 protein circulating in the blood, and in the activity of genes that are regulated by the DUX4 protein.
People in the group will be given del-brax by infusion into the bloodstream at a dose of 2 mg/kg every six weeks. Early FORTITUDE findings presented by Avidity this year showed that three doses of del-brax at 2 mg/kg led to reductions in DUX4-regulated gene activity relative to a placebo group. Early results also showed trends toward improved muscle function after four months on therapy, and no major safety issues were reported.
The FDA has granted del-brax fast track and orphan drug designations, which are designed to incentivize and speed the development of promising new therapies.
FORTITUDE is expected to conclude in April 2027. Patients who finish the main trial are being invited to enroll in its open-label extension study, the Phase 2 FORTITUDE-OLE trial (NCT06547216), assessing del-brax’s safety, tolerability, and efficacy over about two years of treatment.
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