RARE Daily

FDA Grants Fulcrum Fast Track for FSHD Drug

May 12, 2021

The U.S. Food and Drug Administration granted Fast Track designation to Fulcrum Therapeutics’ losmapimod for the potential treatment of facioscapulohumeral muscular dystrophy.

Photo: Judith Dunn, Fulcrum’s president of research and development

Facioscapulohumeral muscular dystrophy (FSHD) is a rare, progressive, and disabling disease for which there are no approved treatments. FSHD is caused by aberrant expression of DUX4 in skeletal muscle, resulting in the inappropriate presence of the DUX4 protein, which causes the death of muscle and its replacement by fat.

Losmapimod is a selective p38α/β mitogen activated protein kinase (MAPK) inhibitor that was exclusively in-licensed from GSK by Fulcrum Therapeutics following Fulcrum’s discovery of the role of p38α/β inhibitors in the reduction of DUX4 expression and an extensive review of known compounds. Utilizing its internal product engine, Fulcrum discovered that inhibition of p38α/β reduced expression of the DUX4 gene in muscle cells derived from patients with FSHD.

Fast Track designation is intended to facilitate development and expedite the review of drugs that treat serious conditions so an approved product can reach the market expeditiously. It enables the company to have more frequent interactions with the FDA throughout the drug development process and allows for eligibility for priority review and accelerated approval in certain cases, as well as a rolling review.

Although losmapimod has never previously been explored in muscular dystrophies, it has been evaluated in more than 3,600 subjects in clinical trials across FSHD and multiple other indications, including in several phase 2 trials and a phase 3 trial. No safety signals were attributed to losmapimod in any of these trials. Fulcrum is currently conducting phase 2 trials investigating the safety, tolerability, and efficacy of losmapimod to treat the root cause of FSHD.

The company is on track to report full data from ReDUX4, a phase 2b randomized, double-blind, placebo-controlled trial of losmapimod in FSHD patients, at the virtual FSHD International Research Congress taking place June 24-25, 2021. Data will include the primary endpoint, reduction from baseline of DUX4-driven gene expression, as well as a pre-specified sensitivity analysis assessing biopsies with the highest pre-treatment level of DUX4-driven gene expression. Additional data to be reported include secondary endpoints evaluating disease progression via skeletal muscle MRI, exploratory endpoints assessing muscle function measures and patient reported outcomes.

“There are no approved therapies to treat patients with FSHD, and losmapimod is currently the only drug in clinical development for this serious and debilitating disease,” said Judith Dunn, Fulcrum’s president of research and development.

She said the FDA’s decision to grant Fast Track designation “demonstrates the potential for losmapimod to address unmet medical needs for people living with FSHD.”

Author: Rare Daily Staff

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