Arrowhead Begins ARO-DM1 Phase 1/2a Trial for DM1

Arrowhead Pharmaceuticals has initiated a Phase 1/2a clinical trial for its RNA interference therapeutic, ARO-DM1, targeting type 1 myotonic dystrophy (DM1), a prevalent form of adult-onset muscular dystrophy. The study, involving up to 48 participants, is designed to assess the safety, tolerability, and pharmacodynamics of ARO-DM1 through single and multiple ascending doses in a double-blind, placebo-controlled setting.

DM1 is characterized by progressive muscle weakness, myotonia, cataracts, and potential cardiac issues, often leading to physical disability and a reduced life expectancy. Currently, there is no cure or disease-modifying treatment available; management focuses on alleviating symptoms through physical therapy and supportive devices.

The ARO-DM1 therapy is engineered to decrease the activity of the dystrophia myotonica protein kinase (DMPK) gene in muscles. The condition arises from an expanded CUG repeat sequence in the DMPK gene, causing disruptions in RNA splicing, a phenomenon known as spliceopathy, which is linked to the disease's clinical features.

Encouraging preclinical results were presented at the 2024 Muscular Dystrophy Association's Clinical & Scientific Conference. The data indicated that ARO-DM1 achieved over 80% reduction in DMPK levels in skeletal muscles of nonhuman primates, with the effect lasting more than 85 days. In a mouse model with a DMPK transgene, a modified version of ARO-DM1, S-ARO-DM1, was successful in lowering DMPK-CUG expression and correcting spliceopathies.

Arrowhead Pharmaceuticals is dedicated to developing medicines that silence disease-causing genes using RNAi technology. Their therapies aim to trigger rapid and sustained suppression of target genes, leveraging the body's natural gene-silencing mechanism.