Balancing Safety and Efficacy in Developing Therapeutic for Rare Neuromuscular Diseases: Douglas Sproule, MD, MSc

WATCH TIME: 5 minutes

"The challenge is how we design studies. We still have to meet the same thresholds and expectations as far as demonstrating the safety and efficacy of a potential therapy. Thus, our study is built around the premise of keeping patients stable and preventing further decline, which would be a tremendous advance for the field."

Limb-girdle muscular dystrophy type 2I/R9 (LGMD2I/R9), a rare neuromuscular disease, is a monogenic autosomal recessive condition that is caused because of partial loss of function mutations in the fukutin-related protein gene. These fukutin-related protein mutations impair glycosylation of αDG, an important protein that is associated with the stabilization of muscle cells. Despite the ongoing challenges that come with developing safe and effective therapies for rare diseases such as LGMD2I/R9, dedication to these efforts remains important.

BBP-418 (BridgeBio Pharma), an investigational treatment in development for patients with LGMD2I/R9, is currently being assessed on safety and efficacy in a randomized, double-blind, placebo-controlled study called FORTIFY (NCT05775848). Recently, BridgeBio Pharma announced the first patient dosed with BBP-418 in FORTIFY.¹ The trial has a planned interim analysis at 12 months to assess glycosylated αDG and will assess participants using the North Star Assessment for Dysferlinopathy along with many other secondary end points.

Douglas Sproule, MD, MSc, chief medical officer at ML Bio Solutions, an affiliate of BridgeBio, recently sat down with NeurologyLive® in an interview to discuss how the double-blind randomized controlled trial approach addresses challenges in rare disease drug development. He also talked about the primary end points and measures that are being used to evaluate potential treatment effect in FORTIFY. In addition, Sproule spoke about the reasons behind the trial, and why patient stability is considered a significant achievement when investigating potential treatments.

REFERENCES
1. BridgeBio pharma announces opportunity for accelerated approval pathway in limb-girdle muscular dystrophy type 2i (lgmd2i/r9) based on glycosylated alpha-dystroglycan (⍺dg) levels and announces first patient dosed in fortify phase 3 study. News Release. BridgeBio Pharma. Published July 31, 2023. Accessed September 15, 2023. https://investor.bridgebio.com/news-releases/news-release-details/bridgebio-pharma-announces-opportunity-accelerated-approval