Revolutionizing RNA therapeutics - Avidity Biosciences

What It Covers

Sarah Boyce, CEO of Avidity Biosciences, explains how the company solved RNA delivery to skeletal muscle and cardiac tissue using antibody-conjugated therapeutics. She details clinical development strategies for myotonic dystrophy and FSHD programs, FDA negotiations for accelerated approval pathways, and building a platform technology company targeting rare genetic diseases.

Key Questions Answered

• •Antibody-Conjugated RNA Delivery: Avidity uses antibodies to target RNA therapeutics to specific cell types outside the liver, solving a fundamental delivery challenge. The platform enables siRNA delivery to skeletal muscle and cardiac tissue, with three neuromuscular programs in late-stage development for populations of 30,000-40,000 patients each in the US, opening entirely new therapeutic spaces.
• •VHUD Primary Endpoint Strategy: Avidity negotiated with FDA to use Video-recorded Home-based Unified Dystrophy assessment as the primary endpoint for myotonic dystrophy phase 3 trials, with hand grip strength, quantitative muscle testing, and quality of life as key secondaries. The 30-week submission timeline creates an accelerated full approval pathway, establishing precedent for other rare disease programs.
• •Biomarker-Driven Acceleration for FSHD: The FORTITUDE study design includes parallel cohorts: Cohort C uses circulating biomarkers and plasma creatine kinase for potential accelerated approval, while Cohort D runs simultaneously as a functional study for full approval. This dual-track approach minimizes time risk if accelerated pathway fails, with both cohorts enrolling under one umbrella protocol for efficiency.
• •FDA Center Inconsistency Challenge: CDER and CBER apply different standards for rare disease approvals, creating up to one-year market access differences for similar drugs. Congress and Senate appropriations language now addresses this disparity. Platform technology companies can potentially leverage safety and efficacy data across programs, though consistent regulatory frameworks remain under development across centers.
• •Reachable Workspace Clinical Meaningfulness: The endpoint measures arm movement range, directly correlating to daily activities like brushing teeth, washing hair, or reaching cupboards. FSHD patients in their 20s-30s lose these capabilities as the disease progresses. Four-month data showed functional improvements earlier than the anticipated 12-month timeline, with downstream DUX4-regulated genes demonstrating reduced inflammation and cellular apoptosis markers.