Treatment with antibody oligonucleotide conjugate led to improved outcomes in DM1

Key takeaways:

• Patients saw significant improvements shown in hand grip strength, muscle strength and range of motion.
• All reported adverse events were mild or moderate, and none were related to the therapeutic.

Long-term treatment with IV administration of a novel therapeutic for those with myotonic dystrophy type 1 led to significant improvement in muscle strength and control and improved quality of life, data show.

“Myotonic dystrophy type 1 is a rare, autosomal-dominant, progressive neuromuscular disease caused by the expansion of the CTG repeat in the untranslated region of the DM1 protein kinase gene, leading to sequestration of RNA-regulating proteins, and consequently the mis-splicing of multiple downstream genes which results in multiorgan manifestations,” John W. Day, MD, PhD, a professor of neurology and pediatrics and director of the Division of Neuromuscular Medicine at Stanford University School of Medicine, and study co-authors wrote in a poster at the 2024 MDA Clinical & Scientific Conference.

Day and colleagues sought to evaluate long-term safety and tolerability of antibody oligonucleotide conjugate AOC 1001 in adults with myotonic dystrophy type 1 (DM1), for which no disease-modifying therapies currently exist.

Their phase 2 open-label extension of the MARINA study included 37 individuals out of the original 38 who completed the parent 6-month MARINA trial, in which AOC 1001 was administered intravenously at quarterly intervals over 24 months.

In the OLE, all those in the parent study initially given 2 mg/kg continued on the same dose, eventually escalating to 4 mg/kg, while those initially given 4 mg/kg remained on the same dose.

Primary outcomes for the extension were improvements at 1 year in myotonia as measured by the Video Hand Opening Time (vHOT), hand grip strength, muscle strength in extremities via the six-muscle Quantitative Muscle Testing (QMT) total score and improvement in activities of daily living measured by the DM1-Activ. Safety concerns were tracked by analysis of adverse events.

As of January, more than 265 infusions of AOC 1001 have occurred, resulting in 61.1 patient-years of exposure to the novel therapeutic.

Data showed continued significant improvement in mean change from the parent study to OLE in myotonia via vHOT hand grip strength, strength in extremities through QMT as well as daily living via DM1-Activ.

Adverse events were reported in 95% of the OLE population (35 of 37), with 9 of 37 connected to the study drug and 4 recorded serious adverse events. All were mild or moderate in nature. No serious adverse events were related to the therapeutic and there were no AEs leading to discontinuation or death.

"The favorable long-term safety data and consistent, durable improvement in myotonia, muscle strength and patient-reported outcomes measures show the potential of del-desiran to make a meaningful difference in the lives of DM1 patients,” Day said in a related release. “I am very encouraged by the prospect of del-desiran as a potential treatment for [myotonic dystrophy type 1]."

Reference:

Avidity Biosciences Announces Positive AOC 1001 Long-term Data Showing Reversal of Disease Progression in People Living with Myotonic Dystrophy Type 1 Across Multiple Endpoints; Same Key Endpoints Agreed for Phase 3 HARBOR Trial. https://aviditybiosciences.investorroom.com/2024-03-04-Avidity-Biosciences-Announces-Positive-AOC-1001-Long-term-Data-Showing-Reversal-of-Disease-Progression-in-People-Living-with-Myotonic-Dystrophy-Type-1-Across-Multiple-Endpoints-Same-Key-Endpoints-Agreed-for-Phase-3-HARBOR-TM-Trial. Published March 4, 2024. Accessed March 5, 2024.