Avidity Announces Unprecedented AOC 1020 Data from Phase 1/2 FORTITUDE™ Trial Demonstrating Greater Than 50 Percent Reduction in DUX4 Regulated Genes and Trends of Functional Improvement in People Living with Facioscapulohumeral Muscular Dystrophy
Avidity Biosciences announced positive results from its Phase 1/2 FORTITUDE trial for AOC 1020 (delpacibart braxlosiran), targeting facioscapulohumeral muscular dystrophy (FSHD). The therapy showed over 50% reduction in DUX4 regulated genes and improvements in muscle strength and function after four months at a 2 mg/kg dose. All adverse events were mild or moderate. The company plans to accelerate the registrational cohorts of the trial. Delpacibart braxlosiran directly targets the root cause of FSHD, a rare genetic disorder with no approved treatments. The data will be presented at the FSHD Society International Research Congress. The company also hosted a virtual investor event to discuss these findings.
- Over 50% reduction in DUX4 regulated genes observed.
- Improvements in muscle strength and function noted.
- All adverse events were mild or moderate.
- Plans to accelerate registrational cohorts.
- Data to be presented at a major research congress.
- First investigational therapy targeting the root cause of FSHD.
- No serious adverse events reported.
- Data currently to a small cohort of 39 participants.
- Long-term safety and efficacy remain unproven.
- No serious adverse events but mild to moderate ones could still be of concern.
- No existing approved therapies to draw comparative conclusions.
Insights
The initial data from the Phase 1/2 FORTITUDE™ trial for delpacibart braxlosiran (del-brax) is highly significant for both the medical community and investors. The observed greater than 50% reduction in DUX4 regulated genes is unprecedented in treatments for Facioscapulohumeral Muscular Dystrophy (FSHD), a condition with no current approved therapies. This not only sets a new benchmark but also demonstrates the viability of Avidity’s Antibody Oligonucleotide Conjugates (AOCs™) as a therapeutic platform.
The trial’s preliminary results also indicated positive trends in muscle strength and function improvements in patients, suggesting that del-brax may not just slow down the progression of FSHD but potentially improve the quality of life for patients. For a condition marked by progressive muscle weakness, these trends could eventually lead to more significant functional gains if sustained or improved in later trials.
Safety data is another critical aspect here. All adverse events reported were mild or moderate, with no serious adverse events or discontinuations. This favorable safety profile is important for advancing to later-phase trials, giving confidence to stakeholders and regulatory bodies alike.
For investors, the positive initial data from the FORTITUDE™ trial has substantial implications. First, the performance of del-brax in reducing DUX4 regulated genes by over
The decision to expedite the initiation of registrational cohorts is a strategic move that could accelerate the path to market, benefiting shareholders by potentially shortening the time horizon for generating revenue. Moreover, Avidity’s data strengthens its overall value proposition, showcasing the robustness of its AOC platform, which could attract partnerships or acquisition interest from larger pharmaceutical companies.
In terms of financial metrics, the favorable safety and tolerability profile reported reduces the risk of costly late-stage trial failures and supports a positive risk-reward profile for the stock. Investors should monitor upcoming milestones closely, as these could serve as key catalysts for stock price movements.
The announcement is poised to have a ripple effect in the market, particularly among companies focused on rare genetic disorders. Del-brax’s promising data not only sets a new standard in FSHD treatment but also enhances Avidity’s competitive positioning. By being the first to demonstrate significant reductions in DUX4 regulated genes, Avidity could solidify a leadership position in RNA therapeutics for muscle diseases.
This development also highlights the growing importance of addressing unmet medical needs in rare diseases. The potential market for FSHD treatments, while niche, represents a high-value segment due to the lack of existing therapies. The broader market implication is a likely increase in investor interest in companies pursuing similar innovative therapies, potentially driving up valuations in this space.
Moreover, the favorable initial data and strategic acceleration in trial phases could set a precedent for other biotech firms in terms of rapidly advancing promising candidates through development pipelines. This could influence market dynamics, where speed to market becomes as important as efficacy and safety in drug development strategies.
Avidity plans to accelerate the initiation of registrational cohorts in FORTITUDE™ trial
Delpacibart braxlosiran (AOC 1020), the first investigational therapy to target the underlying cause of FSHD, provided greater than
Trends of functional improvement including muscle strength, reachable workspace, and positive trends in patient and clinician reported outcomes demonstrated in people treated with delpacibart braxlosiran 2 mg/kg at four months
Delpacibart braxlosiran data demonstrate favorable safety and tolerability with all adverse events mild or moderate
Volume 9 of virtual investor and analyst series today, Wednesday, June 12 at 8:00 a.m. ET
Del-brax is the first investigational therapy designed to treat the underlying cause of FSHD, which is caused by the abnormal expression of a gene called double homeobox 4 or DUX4. FSHD is a rare, hereditary disorder marked by life-long, relentless loss of muscle function, significant pain, fatigue, and progressive disability. Currently, there are no approved therapies for the treatment of FSHD.
"As the first therapy to directly target DUX4, it is very encouraging to see that the del-brax data demonstrate consistent reductions in DUX4 regulated genes and provided trends of functional improvement in patients with FSHD at the four-month timepoint. These early data would support the notion that del-brax has the potential to change the course of disease for people living with FSHD," said Jeffrey M. Statland, M.D., Professor of Neurology, University of Kansas Medical Center, and FORTITUDE™ trial investigator. "Early data showing trends in del-brax to improve muscle strength and function are very encouraging for patients with FSHD who are in need of treatments to prevent the muscle weakness and disability that is associated with this relentlessly, progressive disease."
The AOC 1020 initial data will be highlighted in an oral presentation at the 31st Annual FSHD Society International Research Congress, being held June 13-14, 2024, in
"With the unprecedented del-brax data from the FORTITUDE trial, we are now focused on accelerating our registrational plans as we understand the urgency to develop a treatment for people living with FSHD who have no treatment options," said Sarah Boyce, president and chief executive officer at Avidity. "By directly targeting the root cause of FSHD, we believe that del-brax has the potential to be a first-in-class, best-in-class therapy for people living with FSHD. This is our third rare muscle disease program to show delivery to muscle and target engagement and second therapy to provide signs of functional improvement in patients with rare neuromuscular diseases, further reinforcing the promise of our AOC platform to profoundly improve people's lives by revolutionizing the delivery of RNA therapeutics."
The initial assessment from the randomized, double-blind, placebo-controlled Phase 1/2 FORTITUDE trial of del-brax provides a four-month look at the safety and tolerability for all 39 participants across two dose levels (2 mg/kg and 4 mg/kg). For the four-month assessment in the 2 mg/kg cohort, participants received a single-dose of 1 mg/kg del-brax followed by two doses of 2 mg/kg del-brax (siRNA dose), or placebo. Data on DUX4 regulated genes, circulating biomarkers and muscle strength and function were assessed from 12 participants in the 2 mg/kg cohort.
In the Phase 1/2 FORTITUDE study, del-brax demonstrated:
- Greater than
50% mean reductions in DUX4 regulated genes across multiple panels for DUX4 regulated gene expression in muscle - All participants treated with del-brax showed reductions greater than
20% in DUX4 regulated genes - Mean reductions of
25% or greater in novel circulating biomarker and creatine kinase - Trends of functional improvements including increased strength in upper and lower limb muscles, and muscle function as measured by reachable workspace (RWS) compared to placebo and the ReSolve natural history study
- Trends of improvement in patient and clinician reported outcomes
- Favorable safety and tolerability with all adverse events (AEs) mild or moderate, no serious adverse events and no discontinuations
"Data from the FORTITUDE trial are very promising for people living with FSHD as the progression of the disease can make it increasingly difficult to perform critical day-to-day activities, pursue work and can affect many aspects of life, including family and social life," said Mark Stone, president and chief executive officer of FSHD Society. "FSHD is one of the most prevalent forms of muscular dystrophy and currently, there are no treatment options. The initial del-brax data offers real hope for those living with the disease, their families, and their caregivers, who are desperately waiting for a treatment."
Video Webcast Information
The company is hosting Volume 9 of its investor and analyst event series on June 12, 2024, beginning at 8:00 a.m. ET to discuss the initial data from the FORTITUDE™ trial of del-brax in people living with 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.
The management team will be joined by Jeffrey M. Statland, M.D., Professor of Neurology, University of Kansas Medical Center, and FORTITUDE™ trial investigator. Dr. Statland is one of the principal investigators in the ReSolve study, an ongoing natural history study being led by the FSHD Clinical Trial Research Network (CTRN).
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 39 adult participants with facioscapulohumeral muscular dystrophy (FSHD). FORTITUDE will evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of del-brax administered intravenously, with the primary objective being the safety and tolerability of del-brax in FSHD patients. Activity of del-brax will be assessed using key biomarkers, including 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 an open-label extension study at the end of the treatment period in the FORTITUDE study. For more information about the FORTITUDE trial, visit the FORTITUDE study website or visit http://www.clinicaltrials.gov and search for NCT05747924.
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. In preclinical studies, a single intravenous dose with the murine version of del-brax prevented development of muscle weakness demonstrated by three functional assays - treadmill running, in vivo force and compound muscle action potential. Del-brax is currently in Phase 1/2 development as part of the FORTITUDE™ trial in adults with FSHD. The
About Facioscapulohumeral Muscular Dystrophy (FSHD)
Facioscapulohumeral muscular dystrophy (FSHD) is a rare, progressive, and variable hereditary muscle-weakening condition marked by significant pain, fatigue, and 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 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 cohorts for the FORTITUDE trial and such cohorts potentially serving as the basis for registration; the status and potential of del-brax as a first-in-class, best-in-class treatment for FSHD; 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. This press release also contains estimates and other statistical data made by independent parties and by us. This data involves a number of assumptions and limitations, and the reader is cautioned not to give undue weight to such estimates.
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 additional clinical holds which may not be timely lifted, recalls or product liability claims; Avidity's planned additional 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
Investor Contact:
Geoffrey Grande, CFA
(619) 837-5014
investors@aviditybio.com
Media Contact:
Navjot Rai
(619) 837-5016
media@aviditybio.com
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SOURCE Avidity Biosciences, Inc.
FAQ
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