Case Study: Rapid Startup Phase 1 Cardiomyopathy CRISPR Gene Therapy

By Alexis Hobbins-White

Hereditary transthyretin amyloidosis (ATTRv) is a very rare genetic disorder, affecting about 1 in 100,000 people in Europe and the U.S.. This first-in-human Phase 1 trial tested an in vivo CRISPR/Cas9 non-viral therapy to reduce mutant transthyretin and slow cardiomyopathy progression. The study had two open-label phases: single-ascending dose and dose expansion. It faced challenges, including strict regulatory review, dispersed patients, and evolving data needs due to frequent protocol changes and safety analyses. Precision Medicine accelerated site activation by shifting investigator focus from neurologists to cardiologists at amyloid centers, improving recruitment.

Key lessons include preparing for intense regulatory scrutiny, selecting investigators based on feasibility, and maintaining agile data and cohort management. These approaches highlight Precision Medicine’s expertise in conducting complex gene-therapy trials for rare diseases.