BridgeBio announces opportunity for accelerated approval pathway in LGMD2I/R9

BridgeBio Pharma announced that, based on discussions with the U.S. Food and Drug Administration, there is a potential path to pursue accelerated approval in the U.S. for BBP-418, an investigational oral substrate supplementation therapy, in patients with limb-girdle muscular dystrophy type 2I. BridgeBio also announced that the first patient with LGMD2I/R9 has been dosed in its Phase 3 FORTIFY clinical trial of BBP-418. To date, the Company has activated over half the planned U.S. clinical sites and is in the process of opening sites in Europe and Australia to support global registration. The Phase 3 FORTIFY registrational study is a randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of BBP-418. FORTIFY has a planned interim analysis at 12 months focused on assessing glycosylated alphaDG as a surrogate endpoint to potentially support an accelerated approval. The North Star Assessment for Dysferlinopathy and secondary endpoints will be evaluated at 36 months, and results are expected to provide confirmatory clinical data. A novel, validated bioassay was developed by BridgeBio to directly measure glycosylated DG levels, which are central to LGMD2I/R9 disease, and may enable monitoring of responses to disease-modifying therapies in LGMD2I/R9 patients. BridgeBio is committed to collaborating with the FDA to address the challenges associated with LGMD2I/R9 drug development, including the potential use of a surrogate endpoint to support an accelerated approval. BBP-418 is designed to supply supraphysiological levels of an endogenous substrate upstream of the mutant FKRP enzyme to help drive residual activity of the enzyme to glycosylate alphaDG, with the goal of stabilizing muscle cells during contraction, and potentially halting further muscle damage. Data from an ongoing open-label Phase 2 study is consistent and encouraging, suggesting that BBP-418 may be well-tolerated and have a positive impact on key endpoints. Updated results on the Company’s novel bioassay and for the Phase 2 clinical trial will be presented at the Annual Congress of the World Muscle Society, taking place in Charleston, South Carolina on October 3 – 7, 2023. If approved, BridgeBio believes BBP-418 could be the first approved orally administered therapy for the treatment of patients with LGMD2I/R9.