8-K: Avidity Biosciences Announces Positive Long-Term Data for Del-desiran in Myotonic Dystrophy Type 1 and Plans Phase 3 Trial

Avidity Biosciences reported positive long-term data from the MARINA-OLE trial showing reversal of disease progression in patients with myotonic dystrophy type 1 (DM1) and announced plans to initiate a Phase 3 trial in the second quarter of 2024.

Summary

• Avidity Biosciences hosted an investor and analyst event on March 4, 2024, to discuss new data for delpacibart etedesiran (del-desiran) from the MARINA-OLE trial in patients with myotonic dystrophy type 1 (DM1).
• The MARINA-OLE trial demonstrated long-term efficacy of del-desiran, with improvements in myotonia, muscle strength, and activities of daily living in 12 participants on 4 mg/kg of the drug.
• The data showed a reversal of disease progression compared to a natural history study called END-DM1, which tracked the disease's progression over one year.
• Del-desiran showed a favorable safety and tolerability profile, with all adverse events considered mild or moderate, no study drug related serious adverse events, and no discontinuations in the MARINA-OLE trial.
• The company plans to initiate its Phase 3 HARBOR trial of del-desiran in the second quarter of 2024, using the same key endpoints as the MARINA-OLE trial and the END-DM1 study.
• The Phase 3 HARBOR trial will enroll 150 participants aged 16 and older, with a 1:1 randomization to del-desiran or placebo, and a primary analysis at week 30.

Sentiment

Score: 8

Explanation: The document presents very positive clinical trial results and a clear path forward with a Phase 3 trial. The long-term efficacy and safety data are encouraging, and patient testimonials add a human element. However, the partial clinical hold and the inherent risks of drug development temper the overall sentiment slightly.

Positives

• Del-desiran demonstrated long-term efficacy in improving myotonia, muscle strength, and activities of daily living in DM1 patients.
• The drug showed a reversal of disease progression compared to natural disease progression.
• The safety and tolerability profile of del-desiran was favorable, with no serious drug-related adverse events or discontinuations.
• The company is on track to initiate the Phase 3 HARBOR trial in Q2 2024.
• Patient testimonials highlighted significant improvements in daily activities and overall well-being.

Negatives

• The company is still working to resolve a partial clinical hold related to a serious adverse event from the Phase 1/2 MARINA trial.
• There is a risk that additional data may be inconsistent with current findings.
• The company is early in its development efforts and the AOC platform is unproven.

Risks

• The partial clinical hold related to a serious adverse event in the Phase 1/2 MARINA trial could delay the clinical development of del-desiran.
• Additional participant data may be inconsistent with the current data, potentially leading to different conclusions.
• Unexpected adverse side effects or inadequate efficacy of the product candidates could delay or limit their development, regulatory approval, and commercialization.
• The company's approach to drug development using the AOC platform is unproven.
• There are potential delays in the commencement, enrollment, data readouts, and completion of clinical trials.
• The company is dependent on third parties for preclinical and clinical testing and product manufacturing.

Future Outlook

Avidity plans to initiate the Phase 3 HARBOR trial of del-desiran in the second quarter of 2024, with the same key endpoints as the MARINA-OLE trial and the END-DM1 study. The company anticipates Phase 1/2 FORTITUDE preliminary data in ~half of participants in Q2 2024 and Phase 1/2 EXPLORE44 patient data in 2H 2024.

Management Comments

• Avidity's management team, including CEO Sarah Boyce and CMO Steve Hughes, presented the data and plans for the Phase 3 trial.
• John W. Day, M.D., Ph.D., from Stanford University, provided expert commentary on the data and the disease.

Industry Context

This announcement is significant in the context of the rare disease space, particularly for myotonic dystrophy type 1, where there are limited treatment options. The positive data and planned Phase 3 trial could position Avidity as a leader in developing RNA therapeutics for this condition.

Comparison to Industry Standards

• The END-DM1 natural history study provides a contemporary data set based upon standard of care, allowing for a direct comparison of del-desiran's efficacy against the natural progression of the disease.
• The use of endpoints such as video hand opening time (vHOT), hand grip, quantitative muscle testing (QMT), and DM1-Activ aligns with industry standards for assessing myotonic dystrophy.
• The design of the Phase 3 HARBOR trial, with a placebo-controlled period and an open-label extension, is consistent with common practices in clinical trials for rare diseases.
• The long-term data from the MARINA-OLE trial, with over 61 patient-years of exposure, provides a robust dataset for assessing the safety and efficacy of del-desiran.

Stakeholder Impact

• Shareholders may react positively to the positive clinical trial data and the advancement to Phase 3.
• Patients with DM1 and their families may have increased hope for a potential treatment.
• Employees of Avidity Biosciences may be motivated by the progress of the drug development program.
• The medical community may be interested in the potential of del-desiran as a treatment for DM1.

Next Steps

• Initiate the Phase 3 HARBOR trial in the second quarter of 2024.
• Continue to analyze data from the MARINA-OLE trial.
• Present the MARINA-OLE data at the MDA Conference.
• Resolve the partial clinical hold related to the serious adverse event.

Key Dates

Keywords

Myotonic Dystrophy Type 1, DM1, delpacibart etedesiran, del-desiran, AOC 1001, RNA therapeutics, MARINA-OLE trial, HARBOR trial, muscle strength, myotonia, clinical trial, rare disease