Avidity Biosciences Pursues Potential Accelerated Approval Path with Initiation of Biomarker Cohort in FORTITUDE™ Trial for Delpacibart Braxlosiran (del-brax/AOC 1020) in People Living with Facioscapulohumeral Muscular Dystrophy
Avidity Biosciences has initiated a biomarker cohort in the Phase 1/2 FORTITUDE™ trial of delpacibart braxlosiran (del-brax) for facioscapulohumeral muscular dystrophy (FSHD). The company is pursuing an accelerated approval path, with enrollment expected to complete in 1H 2025. Initial data showed del-brax 2 mg/kg administered every six weeks achieved >50% reductions in DUX4 regulated genes, ≥25% decreases in novel circulating biomarker and creatine kinase, with trends of functional improvement. The biomarker cohort will assess del-brax's impact on patients aged 16-70, focusing on changes in DUX4 regulated gene expression and biomarkers. Del-brax is the first potential therapy targeting DUX4, the disease-causing gene in FSHD.
Avidity Biosciences ha avviato una coorte di biomarcatori nella fase 1/2 del trial FORTITUDE™ di delpacibart braxlosiran (del-brax) per la distrofia muscolare facioscapoloumerale (FSHD). L'azienda sta perseguendo un percorso di approvazione accelerata, con un completamento delle iscrizioni previsto entro la prima metà del 2025. I dati iniziali hanno mostrato che del-brax 2 mg/kg somministrato ogni sei settimane ha raggiunto riduzioni superiori al 50% nei geni regolati da DUX4, diminuzioni ≥25% di biomarker circolanti nuovi e della creatina chinasi, con tendenze di miglioramento funzionale. La coorte di biomarcatori valuterà l'impatto del del-brax su pazienti di età compresa tra 16 e 70 anni, concentrandosi sui cambiamenti nell'espressione genica regolata da DUX4 e sui biomarcatori. Del-brax è la prima terapia potenziale che mira a DUX4, il gene responsabile della malattia nella FSHD.
Avidity Biosciences ha iniciado una cohorte de biomarcadores en el ensayo FORTITUDE™ de fase 1/2 de delpacibart braxlosiran (del-brax) para la distrofia muscular facioscapulohumeral (FSHD). La compañía está buscando un camino de aprobación acelerada, con la inscripción que se espera completar en la primera mitad de 2025. Los datos iniciales mostraron que del-brax 2 mg/kg administrado cada seis semanas logró reducciones de >50% en los genes regulados por DUX4, disminuciones ≥25% en un nuevo biomarcador circulante y creatina quinasa, con tendencias de mejora funcional. La cohorte de biomarcadores evaluará el impacto de del-brax en pacientes de 16 a 70 años, enfocándose en los cambios en la expresión génica regulada por DUX4 y en los biomarcadores. Del-brax es la primera terapia potencial que se dirige a DUX4, el gen causante de la enfermedad en la FSHD.
Avidity Biosciences는 delpacibart braxlosiran (del-brax)의 facioscapulohumeral 근육 위축증 (FSHD)에 대한 1/2상 FORTITUDE™ 시험에서 바이오마커 코호트를 시작했습니다. 이 회사는 가속 승인 경로를 추구하며, 등록 완료는 2025년 상반기 중으로 예상됩니다. 초기 데이터에 따르면, 2 mg/kg의 del-brax가 6주마다 투여되었을 때 DUX4 조절 유전자에서 50% 이상의 감소, 새로운 순환 바이오마커 및 크레아틴 키나제에서 25% 이상의 감소를 달성했으며, 기능 개선 경향이 보였습니다. 이 바이오마커 코호트는 DUX4 조절 유전자 발현 및 바이오마커의 변화에 초점을 맞추어 16세에서 70세까지의 환자에 대한 del-brax의 영향을 평가할 것입니다. Del-brax는 FSHD의 질병 유발 유전자 DUX4를 목표로 하는 첫 번째 잠재적 치료제입니다.
Avidity Biosciences a lancé une cohorte de biomarqueurs dans l'essai FORTITUDE™ de phase 1/2 de delpacibart braxlosiran (del-brax) pour la dystrophie musculaire facioscapulohumérale (FSHD). L'entreprise suit un chemin d'approbation accélérée, avec une inscription prévue pour se terminer au premier semestre 2025. Les données initiales ont montré que del-brax 2 mg/kg administré toutes les six semaines a permis d'atteindre des réductions de plus de 50 % des gènes régulés par DUX4, des diminutions ≥25 % des nouveaux biomarqueurs circulants et de la créatine kinase, avec des tendances montrant une amélioration fonctionnelle. La cohorte de biomarqueurs évaluera l'impact de del-brax sur des patients âgés de 16 à 70 ans, en se concentrant sur les changements dans l'expression des gènes régulés par DUX4 et les biomarqueurs. Del-brax est la première thérapie potentielle ciblant DUX4, le gène responsable de la maladie dans la FSHD.
Avidity Biosciences hat eine Biomarker-Kohorte in der Phase 1/2 der FORTITUDE™-Studie von delpacibart braxlosiran (del-brax) zur facioscapulohumeralen Muskeldystrophie (FSHD) initiiert. Das Unternehmen verfolgt einen beschleunigten Genehmigungsweg, wobei die Einschreibung voraussichtlich in der ersten Jahreshälfte 2025 abgeschlossen sein wird. Erste Daten zeigen, dass del-brax 2 mg/kg, der alle sechs Wochen verabreicht wird, >50% Reduktionen in DUX4-regulierten Genen, ≥25% Rückgänge bei neuartigen zirkulierenden Biomarkern und Kreatinkinase erreicht hat, mit Tendenzen zur funktionellen Verbesserung. Die Biomarker-Kohorte wird die Auswirkungen von del-brax auf Patienten im Alter von 16 bis 70 Jahren bewerten, wobei der Fokus auf Veränderungen der DUX4-regulierten Genexpression und Biomarkern liegt. Del-brax ist die erste potenzielle Therapie, die auf DUX4 abzielt, das krankheitsverursachende Gen bei FSHD.
- Initial trial data showed >50% reduction in DUX4 regulated genes
- Demonstrated ≥25% decrease in circulating biomarker and creatine kinase
- Potential for accelerated approval pathway
- First therapy targeting the underlying cause of FSHD (DUX4)
- Favorable safety and tolerability profile in initial data
- None.
Insights
The initiation of a biomarker cohort for delpacibart braxlosiran (del-brax) represents a significant milestone in FSHD drug development. The unprecedented >50% reduction in DUX4 regulated genes and
The selection of the 2 mg/kg dosing every six weeks is strategically sound, showing similar efficacy to higher doses while potentially offering better long-term tolerability. The pursuit of accelerated approval through biomarker-based evidence could significantly expedite the drug's path to market, addressing a critical unmet need in FSHD treatment.
The dual-cohort approach (biomarker and functional) strengthens the clinical development strategy, potentially providing both mechanistic validation and clinical benefit evidence. This comprehensive approach increases the likelihood of regulatory success.
This development positions Avidity Biosciences favorably in the rare disease space, particularly as they advance the first-ever treatment targeting DUX4 in FSHD. The accelerated approval strategy could significantly reduce time-to-market, potentially leading to earlier revenue generation. With no approved treatments for FSHD, del-brax could capture a valuable market position.
The positive initial data and strategic trial design enhance the probability of successful commercialization. The every-six-weeks dosing schedule could provide a competitive advantage in terms of patient compliance and market adoption. The ongoing enrollment in both the biomarker cohort and open-label extension study indicates strong execution of clinical development plans, which typically correlates with increased investor confidence.
Biomarker cohort for delpacibart braxlosiran (del-brax), the first potential therapy to target DUX4, is measuring changes in DUX4 regulated biomarkers; del-brax 2 mg/kg will be administered every six weeks
Enrollment in the del-brax biomarker cohort expected to be completed in 1H 2025; on track to initiate del-brax functional cohort in 1H 2025
In previously reported initial data, del-brax 2 mg/kg every six weeks showed unprecedented and consistent reductions of DUX4 regulated genes, significant decreases in novel circulating biomarker and creatine kinase, and trends of functional improvement at the four-month timepoint
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 function, significant pain, fatigue, and progressive disability.
"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," said Steve Hughes, M.D., chief medical officer at Avidity. "We are very pleased with the del-brax 2 mg/kg data which showed unprecedented and consistent reductions of DUX4-regulated genes, significant decreases in novel circulating biomarker and creatine kinase, and trends of functional improvement with favorable safety and tolerability at the four-month timepoint. 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."
The biomarker cohort in the FORTITUDE trial will assess the impact of del-brax 2 mg/kg every six weeks in people living with FSHD, ages 16-70. The primary endpoints of the study are changes in DUX4 regulated gene expression and DUX4 regulated circulating biomarker.
For people living with FSHD it is important to maintain suppression of DUX4 at all times as aberrant gene expression is toxic to the muscles. Favorable safety and tolerability, as well as decreases in circulating biomarker and creatine kinase levels were similar for patients treated with 2mg/kg or 4mg/kg of del-brax. Due to this similarity, Avidity selected 2 mg/kg of del-brax to be administered every six weeks, designed to ensure continuous suppression of DUX4 for the biomarker and functional cohorts.
In June of this year, 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 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 (AOC 1020) in approximately 100 participants with facioscapulohumeral muscular dystrophy (FSHD). FORTITUDE will evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of del-brax administered intravenously. Activity of del-brax will be 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 will explore the clinical activity of del-brax including measures of mobility and muscle strength as well as patient reported outcomes and quality of life measures. Participants will have the option to enroll in FORTITUDE-OLE, an open-label extension study once participation in the FORTITUDE study is complete. 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 (AOC 1020) in participants with facioscapulohumeral muscular dystrophy (FSHD) who were previously enrolled in the FORTITUDE Phase 1/2 trial. This trial will continue to evaluate the safety, tolerability, PK, PD, and efficacy of del-brax in participants that 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 (AOC 1020)
Del-brax (AOC 1020) 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 muscle diseases: myotonic dystrophy type 1 (DM1), Duchenne muscular dystrophy (DMD) and facioscapulohumeral muscular dystrophy (FSHD). Avidity is broadening the reach of AOCs with its advancing and expanding pipeline including programs in cardiology and immunology through internal discovery efforts and 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.
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: the primary endpoints, design, goals and other details related to the FORTITUDE™ trial and each of its cohorts; the status and clinical development of del-brax, including any potential accelerated approval; Avidity's plans for the FORTITUDE-OLE™ study and the timing thereof; the characterization of safety, tolerability and functional data associated with del-brax from the Phase 1/2 FORTITUDE trial; the impact of such data on the advancement of del-brax; the plans and timing of adding a functional cohort for the FORTITUDE trial and the biomarker and functional cohorts potentially serving as the basis for registration; the potential of Avidity's product candidates to treat rare diseases and Avidity's efforts to bring them to people suffering from applicable diseases; and the potential of AOCs to target a range of different cells and tissues beyond the liver, and to treat cardiac and immunological diseases.
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 those beyond its control, including, without limitation: preliminary results of a clinical trial are not necessarily indicative of final results and additional participant data related to del-brax that continues to become available may be inconsistent with the data produced as of the date hereof, and further analysis of existing data and analysis of new data may lead to conclusions different from those established as of the data cutoff; unexpected adverse side effects to, or inadequate efficacy of, Avidity's product candidates that may delay or limit their development, regulatory approval and/or commercialization, or may result in clinical holds which may not be timely lifted, recalls or product liability claims; Avidity's current and planned cohorts in the FORTITUDE trial may not support the registration of del-brax; Avidity is early in its development efforts; Avidity's approach to the discovery and development of product candidates based on its AOC platform is unproven, and the company does not know whether it will be able to develop any products of commercial value; potential delays in the commencement, enrollment, data readouts and completion of preclinical studies or clinical trials; Avidity's dependence on third parties in connection with preclinical and clinical testing and product manufacturing; regulatory developments in
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SOURCE Avidity Biosciences, Inc.
FAQ
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