Avidity Reports Positive Data for Experimental DM1 Therapy

Rare Daily Staff

Avidity Biosciences reported positive topline data from the phase 1/2 MARINA clinical trial of antibody oligonucleotide conjugate AOC 1001 for the treatment of myotonic dystrophy type 1, a rare neuromuscular disease.

Myotonic dystrophy type 1 (DM1) is an underrecognized, progressive, and often fatal disease caused by a triplet-repeat in the DMPK gene, resulting in a toxic gain of function mRNA. The disease is highly variable with respect to severity, presentation, and age of onset, however all forms of DM1 are associated with high levels of disease burden and may cause premature mortality. DM1 primarily affects skeletal and cardiac muscle, however patients can suffer from a constellation of manifestations including myotonia and muscle weakness, respiratory problems, fatigue, hypersomnia, cardiac abnormalities, severe gastrointestinal complications, and cognitive and behavioral impairment. Currently, there are no approved treatments for people living with DM1.

AOC 1001, Avidity’s lead product candidate utilizing its AOC platform, is designed to address the root cause of DM1 by reducing levels of a disease-related mRNA called DMPK. AOC 1001 consists of a proprietary monoclonal antibody that binds to the transferrin receptor 1 (TfR1) conjugated with a siRNA targeting DMPK mRNA. In preclinical studies, AOC 1001 successfully delivered siRNAs to muscle cells, resulting in durable, dose-dependent reductions of DMPK RNA across a broad range of muscles including skeletal, cardiac, and smooth muscles. AOC 1001 is currently in phase 1/2 development with the ongoing MARINA trial in adults with DM1.

The MARINA trial is a randomized, double-blind, placebo-controlled, phase 1/2 clinical trial that enrolled 38 adults with DM1. The primary objective of this study was to evaluate the safety and tolerability of single and multiple ascending doses of AOC 1001 administered intravenously. The MARINA trial assessed the activity of AOC 1001 across key biomarkers, including spliceopathy, an important biomarker for DM1, and knockdown of DMPK mRNA.

Though the phase 1/2 trial was not powered to assess functional benefit, it explored the clinical activity of AOC 1001 in multiple measures of muscle function including myotonia, muscle strength, measures of mobility as well as patient reported outcomes and quality of life measures. Patients have the option to enroll in MARINA-OLE, an open label extension study, at the end of the post-treatment period.

The topline results demonstrate 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 Annual Meeting in Boston.

“Data from MARINA exceeded our expectations and delivered a robust data package to support advancement into a pivotal study,” said Sarah Boyce, president and CEO of Avidity. “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.”

Photo: Sarah Boyce, president and CEO of Avidity