Avidity Biosciences (RNA) Announces Positive Topline Data from AOC 1001 Phase 1/2 MARINA
Avidity Biosciences, Inc. (Nasdaq: RNA), a biopharmaceutical company committed to delivering a new class of RNA therapeutics called Antibody Oligonucleotide Conjugates (AOCs™), today announced positive topline data from the Phase 1/2 MARINA™ clinical trial of AOC 1001 for the treatment of myotonic dystrophy type 1 (DM1) demonstrating functional improvement, DMPK reduction, splicing improvements and a favorable safety and tolerability profile. The AOC 1001 topline data were highlighted in an oral presentation at the 75th American Academy of Neurology (AAN) Annual Meeting in Boston, Mass. AOC 1001, Avidity’s lead clinical program utilizing its AOC platform, is designed to address the root cause of DM1, an underrecognized, progressive and often fatal neuromuscular disease with no approved therapies.
“The AOC 1001 topline data demonstrated directional improvement across a variety of functional assessments in patients with DM1, including myotonia and muscle strength in a six-month period. This result is more than we could have anticipated in such a short time. These AOC 1001 data are remarkable and could make a real impact for people living with DM1,” said Nicholas E. Johnson, M.D., M.Sci., FAAN, associate professor and vice chair of research in the Department of Neurology at Virginia Commonwealth University, and lead investigator in the MARINA trial. “We know from the natural history study that these improvements do not happen without intervention. The AOC 1001 data are very encouraging for people with DM1 who need treatment options that can improve their ability to do necessary, everyday tasks that can be incredibly challenging when living with this disease.”
The Phase 1/2 MARINA trial is a randomized, double-blind, placebo-controlled study designed to evaluate the safety and tolerability of single and multiple ascending doses of AOC 1001 administered intravenously in adults with DM1. Topline data were assessed from a 3:1 randomized study with 38 participants, who were administered one dose of 1 mg/kg AOC 1001, three doses of either 2 mg/kg AOC 1001 or 4 mg/kg of AOC 1001 (reflected as siRNA dose), or placebo. AOC 1001 Phase 1/2 topline data demonstrated:
Directional improvement in multiple functional assessments including measures of myotonia, strength and mobility:Myotonia was measured by video hand opening time (vHOT) and is a hallmark of DM1 where relaxation of key muscle groups is impairedMeasures of strength included the Quantitative Muscle Testing (QMT) total score which is based on six muscle groups from both the upper and lower bodyMobility was assessed by the 10-meter walk run test (10mWRT) and the Timed Up and Go testThe endpoints used in MARINA measure important aspects of the disease and correspond to those utilized in the ongoing END-DM1 natural history studyMeaningful DMPK reduction and splicing changes in participants treated with AOC 1001Splicing changes followed by directional improvements in functional measures at 2 mg/kg and 4mg/kg doses of AOC 1001AOC 1001 demonstrated broad splicing improvements in more than a thousand genes impacted by DM1, confirming activity in the nucleusFavorable safety and tolerability profile of AOC 1001 with most adverse events mild or moderate
“The topline data from the MARINA trial reinforce our belief in the potential for AOC 1001 to be an effective treatment for people living with the devastating impact of DM1. Data from MARINA exceeded our expectations and delivered a robust data package to support advancement into a pivotal study. We are focused on designing the quickest path to bring AOC 1001 to patients and look forward to discussions with the FDA,” said Sarah Boyce, president and chief executive officer at Avidity. “Our vision is to profoundly improve people’s lives by revolutionizing the delivery of RNA therapeutics. These AOC 1001 data further demonstrate the broad and disruptive potential of our proprietary AOC platform to address targets and diseases previously unreachable with existing RNA therapies. We look forward to advancing all three of our clinical development programs while we continue to expand our pipeline in skeletal muscle, cardiology, immunology and other diseases.”
Avidity continues to work with the U.S. Food and Drug Administration (FDA) regarding the partial clinical hold on new participant enrollment in the AOC 1001 program. The company continues to dose the participants at both 2 mg/kg and 4 mg/kg of AOC 1001 in the MARINA open-label extension (MARINA-OLE™) study to evaluate the long-term safety and tolerability of AOC 1001 in participants with DM1 who were previously enrolled in the Phase 1/2 MARINA trial. Avidity remains on track to share a first look at the data from the MARINA-OLE study at the end of 2023.
In-person and Video Webcast InformationThe company is hosting Volume 7 of its investor and analyst event series today in Boston, beginning at 5:30 p.m. ET to discuss the topline safety, biomarker and functional data from the MARINA trial of AOC 1001. In-person registration for the event is accessible here. The event will also be available via a live video webcast and can be accessed on 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 Phase 1/2 MARINA topline presentation at the AAN Annual Meeting will be available on the “Publications” page on Avidity’s website.