Fulcrum Therapeutics Collaborates with Sanofi on Losmapimod for FSHD

Fulcrum Therapeutics, Inc. (Fulcrum), a clinical-stage biopharmaceutical company, has announced a significant collaboration and license agreement with Sanofi for the development and marketing of losmapimod. Losmapimod is an oral small molecule currently under investigation for the treatment of facioscapulohumeral muscular dystrophy (FSHD). This partnership grants Sanofi exclusive rights to commercialize losmapimod in all territories outside the United States, while Fulcrum retains commercialization rights within the U.S.

The deal entails an upfront payment of $80 million to Fulcrum, with potential milestone payments totaling up to $975 million. Additionally, Fulcrum will receive royalties on sales outside the U.S. Both companies will share the future global development costs equally.

FSHD is a genetic, progressive muscular disorder characterized by muscle cell death and fat infiltration into muscle tissue. Losmapimod is currently undergoing a global Phase 3 clinical trial to evaluate its efficacy in treating FSHD. Results from a previous Phase 2 clinical trial, known as ReDUX4, showed that losmapimod could slow disease progression and improve muscle health. Fulcrum anticipates reporting topline data from the Phase 3 trial, REACH, in the fourth quarter of 2024. Following successful results, Fulcrum and Sanofi plan to file marketing applications in the U.S., Europe, Japan, and other regions.

Alex C. Sapir, Fulcrum’s president and CEO, expressed enthusiasm for the partnership. He emphasized that Sanofi's proven track record in developing treatments for rare neuromuscular diseases makes them an ideal partner. This collaboration allows Fulcrum to concentrate on the U.S. market while leveraging Sanofi’s global commercial capabilities. Sapir highlighted the potential of losmapimod to become the first approved treatment for FSHD patients worldwide.

Sanofi’s Global Head of Rare Diseases, Burcu Eryilmaz, also commented on the partnership, noting that it expands Sanofi’s rare disease portfolio. Eryilmaz pointed out that losmapimod has demonstrated meaningful clinical benefits and significant potential to address the unmet need for a safe and effective treatment that slows FSHD progression. Sanofi looks forward to working closely with Fulcrum as losmapimod progresses through late-stage development.

Losmapimod is a selective inhibitor of p38α/β mitogen-activated protein kinase (MAPK). It was exclusively in-licensed by Fulcrum from GSK after Fulcrum discovered its role in reducing DUX4 expression, a key factor in FSHD. Phase 2 trial results indicated that losmapimod not only slowed disease progression but also improved upper extremity strength and functional measures. Despite not having been previously explored in muscular dystrophies, losmapimod has been evaluated in over 3,600 subjects across multiple indications without any significant safety concerns. It has received Fast Track and Orphan Drug designations from the U.S. FDA for FSHD treatment.

FSHD is a severe, rare, and progressive disease with no approved treatments. It leads to fat infiltration of skeletal muscle, causing muscular atrophy, especially in the face, shoulders, upper arms, and abdomen. This results in significant functional impairments, including loss of mobility and chronic pain. It is one of the most common forms of muscular dystrophy, affecting an estimated 30,000 people in the United States alone.

Fulcrum Therapeutics focuses on developing small molecules to treat genetically defined rare diseases. Besides losmapimod, Fulcrum is also developing pociredir for the treatment of sickle cell disease. The company uses proprietary technology to identify drug targets that can modulate gene expression, addressing the root cause of gene mis-expression.