Del-brax FORTITUDE biomarker cohort designed for potential accelerated approval; plan to share regulatory update in Q2 2025
Regulatory alignment on global Phase 3 del-brax trial design and study initiation anticipated in Q2 2025
Plan to present topline data from FORTITUDE dose escalation cohorts in Q2 2025
On track to be first globally approved drug for FSHD
SAN DIEGO, Calif. — Avidity Biosciences, Inc. (Nasdaq: RNA), a biopharmaceutical company committed to delivering a new class of RNA therapeutics called Antibody Oligonucleotide Conjugates (AOCs™), today announced the completion of enrollment in the biomarker cohort in the Phase 1/2 FORTITUDE™ clinical trial of delpacibart braxlosiran (del-brax) in people living with facioscapulohumeral muscular dystrophy (FSHD). A total of 51 participants were enrolled in the FORTITUDE biomarker cohort.
“Completing enrollment in the FORTITUDE biomarker cohort is an important milestone as we pursue a potential accelerated approval path in the U.S. for del-brax and work to bring the first approved drug to people living with this rare, devastating neuromuscular disease who have no treatment options as quickly as possible,” said Steve Hughes, M.D., chief medical officer at Avidity. “We are very encouraged by the del-brax 2 mg/kg data thus far, demonstrating unprecedented and consistent reductions in DUX4-regulated genes, significant decreases in novel circulating biomarker and creatine kinase, trends of functional improvement, and favorable safety and tolerability, and look forward to sharing additional data as well as other key milestones in the second quarter of this year.”
Avidity is on track to deliver multiple updates from the del-brax program in Q2 including:
- Regulatory alignment on a potential accelerated approval path in the U.S. for the ongoing FORTITUDE biomarker cohort;
- Regulatory alignment on the design of the global Phase 3 trial as well as initiation of the trial; and
- Topline data from the dose escalation cohorts in the FORTITUDE trial.
Del-brax is the first investigational therapy designed to treat the underlying cause of FSHD by directly targeting the mRNA transcript of the disease-causing gene, double homeobox 4 (DUX4). Currently, there are no approved therapies for the treatment of FSHD, a rare, hereditary disorder marked by life-long, relentless loss of muscle function, significant pain, fatigue, and progressive disability. FSHD affects approximately 45,000 to 87,000 people in the United States and European Union.
About the Phase 1/2 FORTITUDE™ trial
The FORTITUDE™ trial is a randomized, placebo-controlled, double-blind, Phase 1/2 clinical trial designed to evaluate single and multiple doses of delpacibart braxlosiran or del-brax in 90 participants with facioscapulohumeral muscular dystrophy (FSHD). FORTITUDE is evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of del-brax administered intravenously. Activity of del-brax is being assessed using key biomarkers, including DUX4-regulated muscle and circulating biomarkers and magnetic resonance imaging (MRI) measures of muscle volume and composition. Though the Phase 1/2 trial is not statistically powered to assess functional benefit, it explores the clinical activity of del-brax including measures of mobility and muscle strength as well as patient reported outcomes and quality of life measures.
The trial has a total of three dose cohorts. The first two dose escalation cohorts evaluated 2 mg/kg or 4 mg/kg of del-brax versus placebo and were designed to assess safety as well as inform the dose and dose regimen of del-brax for additional studies. Avidity has completed enrollment in the dose escalation cohorts and identified 2 mg/kg every six weeks of del-brax as the dose for future clinical trials.
The third, ongoing biomarker cohort in the FORTITUDE trial is designed for a potential accelerated approval path in the U.S. It is assessing the impact of del-brax 2 mg/kg every six weeks versus placebo for 12 months in people living with FSHD, ages 16-70. The primary endpoints of the study cohort are changes in DUX4-regulated gene expression and DUX4-regulated circulating biomarker. Enrollment in the biomarker cohort is complete.
Participants who complete FORTITUDE have the option to enroll in the ongoing FORTITUDE open-label extension (FORTITUDE-OLE™) study evaluating the long-term safety and tolerability of del-brax in participants living with FSHD. For more information about the FORTITUDE trial, visit the FORTITUDE study website or visit http://www.
About the Phase 2 FORTITUDE-OLE™ trial
FORTITUDE-OLE™ is an open-label, multi-center trial designed to evaluate the long-term safety and tolerability of delpacibart braxlosiran or del-brax in participants with facioscapulohumeral muscular dystrophy (FSHD) who were previously enrolled in the Phase 1/2 FORTITUDE™ trial. This trial will continue to evaluate the safety, tolerability, PK, PD, and efficacy of del-brax in participants who enrolled in the randomized, placebo-controlled, Phase 1/2 FORTITUDE clinical trial. Participants who enroll in the FORTITUDE-OLE study will receive del-brax regardless of whether they received active treatment or placebo in the FORTITUDE study. The total duration of active treatment with del-brax in the FORTITUDE-OLE is approximately 24 months. Avidity may extend active treatment beyond 24 months at a future timepoint. For more information on the FORTITUDE-OLE study click here or visit http://www.
About Del-brax
Del-brax is designed to treat the underlying cause of FSHD, which is caused by the abnormal expression of a gene called double homeobox 4 or DUX4. The abnormal expression of DUX4 protein leads to changes in gene expression in muscle cells that are associated with the life-long, progressive loss of muscle function in patients with FSHD. Del-brax aims to reduce the expression of DUX4 mRNA and DUX4 protein in muscles in people with FSHD. Del-brax consists of a proprietary monoclonal antibody that binds to the transferrin receptor 1 (TfR1) conjugated with a siRNA targeting DUX4 mRNA. Avidity reported positive initial del-brax 2 mg/kg data at four months from the Phase 1/2 FORTITUDE™ trial demonstrating unprecedented and consistent reductions of greater than 50% in DUX4 regulated genes, trends of functional improvement, and favorable safety and tolerability in people living with FSHD. Del-brax is currently in Phase 1/2 development as part of the FORTITUDE trial in individuals with FSHD. The U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have granted Orphan designation for del-brax and the FDA has granted del-brax Fast Track designation.
About Facioscapulohumeral Muscular Dystrophy (FSHD)
Facioscapulohumeral muscular dystrophy (FSHD) is a rare, progressive, and variable hereditary muscle-weakening condition marked by life-long, relentless loss of muscle function, significant pain, fatigue, and progressive disability. It is characterized by progressive and often asymmetric skeletal muscle loss that initially causes weakness in muscles in the face, shoulders, arms and trunk and progresses to weakness in muscles in the lower body. FSHD is an autosomal dominant disease caused by the aberrant expression of the DUX4 (double homeobox 4) gene in the skeletal muscle, which activates genes that are toxic to muscle cells and leads to a series of downstream events that result in skeletal muscle wasting and compromised muscle function. Skeletal muscle weakness results in physical limitations throughout the whole body, including an inability to lift arms for more than a few seconds, loss of ability to show facial expressions and serious speech impediments. These symptoms cause many people affected by FSHD to become dependent on the use of a wheelchair for mobility. Currently, there are no approved treatments for people living with FSHD.
About Avidity
Avidity Biosciences, Inc.’s mission is to profoundly improve people’s lives by delivering a new class of RNA therapeutics – Antibody Oligonucleotide Conjugates (AOCs™). Avidity is revolutionizing the field of RNA with its proprietary AOCs, which are designed to combine the specificity of monoclonal antibodies with the precision of oligonucleotide therapies to address targets and diseases previously unreachable with existing RNA therapies. Utilizing its proprietary AOC platform, Avidity demonstrated the first-ever successful targeted delivery of RNA into muscle and is leading the field with clinical development programs for three rare neuromuscular diseases: myotonic dystrophy type 1 (DM1), Duchenne muscular dystrophy (DMD) and facioscapulohumeral muscular dystrophy (FSHD). Avidity is also advancing two wholly-owned precision cardiology development candidates addressing rare genetic cardiomyopathies. In addition, Avidity is broadening the reach of AOCs with its advancing and expanding pipeline including programs in cardiology and immunology through key partnerships. Avidity is headquartered in San Diego, CA. For more information about our AOC platform, clinical development pipeline and people, please visit www.aviditybiosciences.
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