Potential FDA Accelerated Approval for Limb-Girdle Muscular Dystrophy 2I/R9 Therapy: Douglas Sproule, MD, MSc

WATCH TIME: 3 minutes

"There's been a tremendous movement revolution over the last several months that's occurred as a result of some of the reforms that the FDA has been gently but very firmly advancing. We're cautiously optimistic that this is a valid pathway, and we're extremely excited at the changes in the increased flexibility the FDA seems to be following in their current guidance."

BBP-418, also known as ribitol, is designed to give supraphysiological levels of an endogenous substrate upstream of the mutant fukutin-related protein enzyme. This then helps drive residual activity of the enzyme to glycosylate α-dystroglycan (αDG) to stabilize the muscle cells during contraction, and potentially stopping any additional muscle damage caused by muscular dystrophies.

In March 2022, preliminary findings from a phase 2 trial (NCT04800874) showedBBP-418 increased glycosylation of αDG, signifying the oral therapy has the potential to address both the root cause of limb-girdle muscular dystrophy type 2I/R9 (LGMD2I/R9), and drive functional improvements for patients.^1,2 Then in recent news, BridgeBio Pharma announced the first patient dosed with BBP-418, an investigational treatment for patients living with LGMD2I/R9, in the randomized, double-blind, placebo-controlled FORTIFY trial (NCT05775848).³

Recently, Douglas Sproule, MD, MSc, chief medical officer at ML Bio Solutions, an affiliate of BridgeBio, sat down with NeurologyLive® in an interview to discuss how recent FDA reforms impacted the neuromuscular field and the agency’s approach to rare disease programs. He talked about the potential benefits and challenges associated with pursuing accelerated approvals such as for this LGMD 2I/R9 therapy. In addition, Sproule spoke about how the FDA plans to determine whether early data readouts provide sufficient evidence for accelerated approval of neuromuscular 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 18, 2023. https://investor.bridgebio.com/news-releases/news-release-details/bridgebio-pharma-announces-opportunity-accelerated-approval