Avidity Biosciences Announces Positive Topline Phase 1/2 FORTITUDE™ Data Demonstrating Consistent Improvement Across Multiple Functional Measures Compared to Placebo in Del-Brax Treated FSHD Participants
• Avidity Biosciences, Inc. (Nasdaq: RNA), a biopharmaceutical company committed to delivering a new class of RNA therapeutics called Antibody Oligonucleotide Conjugates (AOCs™) to profoundly improve people's lives, today announced positive topline data from the dose escalation cohorts of the delpacibart braxlosiran (del-brax) Phase 1/2 FORTITUDE™ program in Facioscapulohumeral Muscular Dystrophy (FSHD).
• These data as well as research supporting KHDC1L as a novel DUX4 regulated circulating biomarker will be presented in oral and poster presentations at the 32nd Annual FSHD Society International Research Congress (IRC), being held June 12-13, 2025, in Amsterdam, the Netherlands.
• Del-brax is the first investigational therapy designed to treat the underlying cause of FSHD by directly targeting 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 strength and function, significant pain, fatigue, and progressive disability.
• FSHD affects approximately 45,000 to 87,000 people in the United States and Europe.
• "The positive topline del-brax results from FORTITUDE being presented at FSHD IRC this week are remarkable and consistent across multiple functional measures as well as biomarkers,"" said Sarah Boyce, president and chief executive officer at Avidity.
• "Based on these unprecedented data, we are rapidly advancing del-brax as we pursue accelerated approval and prepare to submit a BLA in the second half of 2026. We are incredibly grateful for the continued trust and support from study participants, their caregivers, investigators and their staff, which are paramount to the success of this program."
Phase 3 FORWARD™ study beginning- Avidity today also announced that the accelerated approval regulatory pathway in the U.S. is open for del-brax and that the company has initiated the global, confirmatory Phase 3 FORWARD™ study in FSHD.
• "Del-brax data from the FORTITUDE study continue to demonstrate consistent reductions in a novel circulating biomarker across two cohorts at 12 months. I am particularly encouraged that del-brax shows favorable safety and tolerability with early and consistent trends towards benefit with del-brax compared to placebo across multiple functional and participant-reported outcome measures,"" said Jeffrey M. Statland, M.D., Professor of Neurology, University of Kansas Medical Center, and FORTITUDE trial investigator.
• "These data indicate that by directly targeting DUX4, del-brax may be able to improve the lives of patients with FSHD and potentially meaningfully control their disease. I look forward to continued evaluation of del-brax in the FORWARD Phase 3 study and remain hopeful that it is on track to become the potentially first approved drug for FSHD.""
Study Overview
• Randomized, placebo-controlled, double-blind Phase 1/2 clinical trial assessing multiple doses of del-brax.
• Includes an open-label extension study (FORTITUDE-OLE™) for long-term evaluation.
• 39 participants received 2 mg/kg or 4 mg/kg of del-brax vs placebo over 12 months.
• Del-brax was given every six weeks for three months, then every 13 weeks thereafter.
• Improved functional mobility & muscle strength, measured by:
• 10-Meter Walk-Run Test (10MWRT)
• Timed Up and Go (TUG)
• Quantitative Muscle Testing (QMT)
• Better quality of life per patient-reported outcomes.
• Significant reductions in KHDC1L & creatine kinase (muscle damage biomarkers).
• Favorable long-term safety, with most mild/moderate adverse events (AEs) and no serious or severe drug-related events.
• Fully enrolled Phase 1/2 FORTITUDE biomarker cohort topline data expected Q2 2026.
• Primary endpoint: Reduction of KHDC1L, a DUX4-regulated circulating biomarker.
• Developed in collaboration with Dr. Stephen Tapscott, Fred Hutchinson Cancer Center.
• The Company is hosting an investor and analyst event today, June 9, 2025 at 8:00 a.m. ET. Avidity management will be joined by Jeffrey M. Statland, M.D., Professor of Neurology, University of Kansas Medical Center, and FORTITUDE™ trial investigator, to discuss these updates relating to del-brax in FSHD.
• The virtual event will be available via a live video webcast and can be accessed here or from the ""Events and Presentations"" page in the ""Investors"" section of Avidity's website.
• A replay of the webcast will be archived on Avidity's website following the event.
About the Phase 1/2 FORTITUDE™ and Phase 2 FORTITUDE-OLE™ trials
• Randomized, placebo-controlled, double-blind Phase 1/2 clinical trial with 90 participants.
• Assesses safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of intravenous del-brax.
• Measures DUX4-regulated muscle biomarkers, MRI muscle volume/composition, and functional mobility.
• Explores patient-reported outcomes and quality of life measures.
Three cohorts:
• Dose escalation cohorts (2 mg/kg & 4 mg/kg vs placebo) assessed safety and dosing for future studies.
• Biomarker cohort (ongoing): 2 mg/kg every six weeks vs placebo for 12 months (ages 16-70).
• Avidity identified 2 mg/kg every six weeks as the preferred dose for future trials.
Primary Endpoints & Biomarker Assessment
Primary endpoint: Reduction of KHDC1L, a DUX4-regulated circulating biomarker.
Enrollment complete, blinded treatment is ongoing.
Participants completing FORTITUDE™ may enroll in FORTITUDE-OLE™ to assess long-term safety and tolerability.
More details available on ClinicalTrials.gov
FORTITUDE trial (NCT05747924)
FORTITUDE-OLE trial (NCT06547216)
• 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.
• Del-brax is currently in registrational-stage studies including FORTITUDE biomarker cohort and the global, confirmatory, Phase 3 FORWARD 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.
• 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.
• 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.com and engage with us on LinkedIn and X.
The press release contains forward-looking statements, based on Avidity's current beliefs and expectations. Key forward-looking statements include:
• Plans for BLA filing for del-brax and its accelerated FDA approval timeline.
• Regulatory status of accelerated approval as a pathway for del-brax.
• Biomarker selection, topline data from the FORTITUDE™ trial, and global approval efforts.
• Potential impact of del-brax on FSHD patients.
• Progress of the FORTITUDE and FORWARD™ trials, including design, enrollment, and dosage details.
Cautionary Risks & Uncertainties:
• Results from the FORTITUDE trial may not support BLA submission or approval.
• FDA may reject accelerated approval due to biomarker validity concerns.
• Regulatory feedback may evolve, altering initial expectations.
• Potential delays in clinical trials, product development, and manufacturing.
• Avidity's financial challenges, including possible depletion of capital resources.
• External judicial, legislative, and market developments could impact progress.
SEC Filings & Disclosure:
• Risks are detailed in Avidity's Annual Report on Form 10-K (2024) and subsequent filings.
• The company does not guarantee future results and is not obligated to update forward-looking statements.
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