Avidity Biosciences Completes Enrollment in Biomarker Cohort in Phase 1/2 FORTITUDE™ Trial for Delpacibart Braxlosiran (del-brax) in People Living with Facioscapulohumeral Muscular Dystrophy
Avidity Biosciences (Nasdaq: RNA) has completed enrollment of 51 participants in the biomarker cohort of its Phase 1/2 FORTITUDE™ trial for delpacibart braxlosiran (del-brax), targeting facioscapulohumeral muscular dystrophy (FSHD). The company aims to be first to market with an approved FSHD treatment.
Del-brax, at 2 mg/kg dosage, has shown promising results including:
- Unprecedented reductions in DUX4-regulated genes
- Significant decreases in novel circulating biomarker and creatine kinase
- Trends of functional improvement
- Favorable safety and tolerability
Key Q2 2025 milestones include:
- Updates on potential U.S. accelerated approval pathway
- Global Phase 3 trial design alignment and initiation
- Topline data from FORTITUDE dose escalation cohorts
Avidity Biosciences (Nasdaq: RNA) ha completato l'arruolamento di 51 partecipanti nella coorte di biomarcatori del suo trial FORTITUDE™ di fase 1/2 per delpacibart braxlosiran (del-brax), mirato alla distrofia muscolare facioscapoloumerale (FSHD). L'azienda punta a essere la prima a commercializzare un trattamento approvato per la FSHD.
Del-brax, alla dose di 2 mg/kg, ha mostrato risultati promettenti, tra cui:
- Riduzioni senza precedenti nei geni regolati da DUX4
- Significative diminuzioni di un nuovo biomarcatore circolante e della creatina chinasi
- Tendenze di miglioramento funzionale
- Sicurezza e tollerabilità favorevoli
Le principali scadenze per il secondo trimestre del 2025 includono:
- Aggiornamenti sul potenziale percorso di approvazione accelerata negli Stati Uniti
- Allineamento e avvio del design del trial globale di fase 3
- Dati preliminari dalle coorti di escalation della dose FORTITUDE
Avidity Biosciences (Nasdaq: RNA) ha completado la inscripción de 51 participantes en la cohorte de biomarcadores de su ensayo FORTITUDE™ de fase 1/2 para delpacibart braxlosiran (del-brax), dirigido a la distrofia muscular facioscapulohumeral (FSHD). La empresa tiene como objetivo ser la primera en comercializar un tratamiento aprobado para la FSHD.
Del-brax, a una dosis de 2 mg/kg, ha mostrado resultados prometedores, que incluyen:
- Reducciones sin precedentes en los genes regulados por DUX4
- Disminuciones significativas en un nuevo biomarcador circulante y en la creatina quinasa
- Tendencias de mejora funcional
- Seguridad y tolerabilidad favorables
Los hitos clave para el segundo trimestre de 2025 incluyen:
- Actualizaciones sobre el posible camino de aprobación acelerada en EE. UU.
- Alineación e inicio del diseño del ensayo global de fase 3
- Datos preliminares de las cohortes de escalada de dosis de FORTITUDE
Avidity Biosciences (Nasdaq: RNA)는 delpacibart braxlosiran (del-brax)의 1/2상 FORTITUDE™ 시험에서 바이오마커 코호트에 51명의 참가자 등록을 완료했습니다. 이 치료제는 안면견갑상완근육위축증(FSHD)을 목표로 하고 있습니다. 회사는 FSHD 치료제로 승인된 제품을 최초로 시장에 출시할 계획입니다.
del-brax는 2 mg/kg 용량에서 다음과 같은 유망한 결과를 보여주었습니다:
- DUX4에 의해 조절되는 유전자의 전례 없는 감소
- 새로운 순환 바이오마커 및 크레아틴 키나제의 유의미한 감소
- 기능적 개선의 경향
- 우호적인 안전성 및 내약성
2025년 2분기의 주요 이정표는 다음과 같습니다:
- 미국의 가속 승인 경로에 대한 업데이트
- 글로벌 3상 시험 설계 조정 및 시작
- FORTITUDE 용량 증가 코호트의 주요 데이터
Avidity Biosciences (Nasdaq: RNA) a terminé l'inscription de 51 participants dans la cohorte de biomarqueurs de son essai FORTITUDE™ de phase 1/2 pour delpacibart braxlosiran (del-brax), visant la dystrophie musculaire facioscapulohumérale (FSHD). L'entreprise vise à être la première à commercialiser un traitement approuvé pour la FSHD.
Del-brax, à une posologie de 2 mg/kg, a montré des résultats prometteurs, notamment:
- Des réductions sans précédent des gènes régulés par DUX4
- Des diminutions significatives d'un nouveau biomarqueur circulant et de la créatine kinase
- Des tendances d'amélioration fonctionnelle
- Une sécurité et une tolérance favorables
Les principales étapes clés pour le deuxième trimestre 2025 comprennent:
- Mises à jour sur le potentiel chemin d'approbation accéléré aux États-Unis
- Alignement et lancement du design de l'essai mondial de phase 3
- Données préliminaires des cohortes d'escalade de dose de FORTITUDE
Avidity Biosciences (Nasdaq: RNA) hat die Rekrutierung von 51 Teilnehmern in der Biomarker-Kohorte seiner Phase 1/2 FORTITUDE™-Studie für delpacibart braxlosiran (del-brax) abgeschlossen, die auf die facioscapulohumerale Muskelatrophie (FSHD) abzielt. Das Unternehmen strebt an, der Erste zu sein, der ein genehmigtes FSHD-Medikament auf den Markt bringt.
Del-brax hat bei einer Dosierung von 2 mg/kg vielversprechende Ergebnisse gezeigt, darunter:
- Ohnegleichen Rückgänge bei DUX4-regulierten Genen
- Signifikante Abnahmen eines neuen zirkulierenden Biomarkers und der Kreatinkinase
- Tendenzen zur funktionalen Verbesserung
- Günstige Sicherheit und Verträglichkeit
Wichtige Meilensteine im 2. Quartal 2025 umfassen:
- Aktualisierungen zum möglichen beschleunigten Genehmigungsweg in den USA
- Ausrichtung und Initiierung des globalen Phase-3-Studien-Designs
- Erste Daten aus den Dosissteigerungskohorten von FORTITUDE
- Completed enrollment of 51 participants in FORTITUDE biomarker cohort
- Demonstrated strong efficacy with unprecedented DUX4-regulated gene reductions
- Potential accelerated approval pathway in the U.S.
- First-to-market opportunity with no current approved treatments
- Significant addressable market of 45,000-87,000 patients in US/EU
- Phase 3 trial yet to begin
- Regulatory approvals still pending
- Competition may emerge before final approval
Insights
The completion of enrollment in the biomarker cohort of Avidity's Phase 1/2 FORTITUDE trial represents a significant milestone in the development of delpacibart braxlosiran (del-brax) for FSHD. With 51 participants enrolled, this biomarker cohort is specifically designed to support a potential accelerated approval pathway, which could substantially shorten the time to market for this first-in-class therapy.
The preliminary efficacy signals are particularly encouraging. The 2 mg/kg dose has demonstrated consistent reductions in DUX4-regulated genes (the disease-causing protein in FSHD), decreases in circulating biomarkers and creatine kinase (indicating reduced muscle damage), and trends toward functional improvement. This molecular target engagement coupled with initial clinical signals provides a strong foundation for the accelerated approval strategy.
Most importantly, Avidity has aligned their development timeline with multiple key readouts in Q2 2025: regulatory feedback on the accelerated approval path, Phase 3 trial design finalization, trial initiation, and topline data from dose escalation cohorts. For a rare disease affecting 45,000-87,000 patients in the US and EU with no approved therapies, this represents a potentially transformative advance.
The biomarker-based approach is particularly relevant for FSHD, where disease progression is slow and variable. If successful, this could become a model for efficient development in other rare neuromuscular conditions while potentially validating Avidity's broader AOC platform technology.
Avidity's announcement marks a critical inflection point in their FSHD program development timeline. Completing enrollment in the biomarker cohort designed for potential accelerated approval is strategically significant as it positions del-brax as the leading candidate to become the first approved therapy for this debilitating rare neuromuscular disease.
The clustering of multiple catalysts in Q2 2025 creates a highly concentrated period of potential value creation. These include regulatory feedback on accelerated approval, Phase 3 trial design finalization and initiation, plus topline data from dose escalation cohorts. This convergence of milestones in a single quarter represents an unusually rich period of developmental progress for a clinical-stage biotech.
Early efficacy signals at the 2 mg/kg dose demonstrating target engagement (DUX4 reduction) alongside favorable safety provide increasing confidence in the program's potential. The biomarker strategy aligns with FDA's increased receptivity to surrogate endpoints in areas of high unmet need, potentially allowing Avidity to leapfrog traditional development timelines.
For a rare disease affecting 45,000-87,000 patients with no approved therapies, securing first-mover advantage could establish del-brax as the standard of care before competitors reach market. With this progress, Avidity continues building evidence supporting their novel Antibody Oligonucleotide Conjugate platform, which has implications beyond this single indication and could transform RNA therapeutic delivery more broadly.
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
"Completing enrollment in the FORTITUDE biomarker cohort is an important milestone as we pursue a potential accelerated approval path in the
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
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
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.clinicaltrials.gov and search for NCT05747924.
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.clinicaltrials.gov and search for NCT06547216.
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
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
Forward-Looking Statements
Avidity cautions readers that statements contained in this press release regarding matters that are not historical facts are forward-looking statements. These statements are based on the company's current beliefs and expectations. Such forward-looking statements include, but are not limited to, statements regarding: Avidity's plans to present topline data from the dose escalation cohorts of the FORTITUDE study and the timing thereof; Avidity's plans to pursue an accelerated approval path for del-brax and the anticipation of regulatory alignment with such plans; the status of the FORTITUDE trial and cohorts therein, including but not limited to initiation, enrollment, design and goals; the ability for del-brax to achieve accelerated approval; the characterization of data associated with del-brax and the FORTITUDE trial, the conclusions drawn therefrom, the impact of such data on the advancement of del-brax and its abilities to treat FSHD; and the possibility of del-brax becoming the first globally approved drug for FSHD.
The inclusion of forward-looking statements should not be regarded as a representation by Avidity that any of these plans will be achieved. Actual results may differ from those set forth in this press release due to the risks and uncertainties inherent in Avidity's business and beyond its control, including, without limitation: the data and results produced in the FORTITUDE trial and FORTITUDE-OLE as of the most recent respective cutoff dates may not be indicative of final results, may not support BLA submissions or accelerated approvals, may not be satisfactory to the FDA and other regulators, and new analyses of existing data and results may produce different conclusions than established as of the date hereof; even if approved, Avidity may not be able to execute a successful product launch for del-brax; unexpected adverse side effects to, or inadequate efficacy of, del-brax that may delay or limit its development, regulatory approval and/or commercialization; later developments with the FDA and other global regulators that could be inconsistent with the feedback received to date; Avidity's approach to the discovery and development of product candidates based on its AOC™ platform is unproven and may not produce any products of commercial value; potential delays in the commencement, enrollment, data readouts and completion of clinical trials; Avidity's dependence on third parties in connection with clinical testing and product manufacturing; legislative, judicial and regulatory developments in
Investor Contact:
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investors@aviditybio.com
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SOURCE Avidity Biosciences, Inc.
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