Sanofi invests $80M in Fulcrum drug for phase 3 rare disease pipeline

Sanofi has agreed to invest $80 million upfront on a drug previously shelved by GSK, with an additional commitment of up to $975 million in milestone payments. The drug, a p38 inhibitor known as losmapimod, is being developed for the treatment of facioscapulohumeral muscular dystrophy (FSHD), a progressive muscle-wasting disorder. Fulcrum Therapeutics, which secured the rights to losmapimod from GSK in 2019, will retain U.S. rights while Sanofi acquires rights outside the U.S.

Fulcrum is conducting a phase 3 clinical trial involving 260 participants to determine the efficacy of losmapimod for FSHD, with results expected in the fourth quarter. The company aims to gain approval for the drug both in the U.S. and internationally. Sanofi plans to seek regulatory approval in Europe, Japan, and other regions if the trial results are positive.

If approved, losmapimod could become the first treatment for FSHD, which affects approximately 30,000 individuals in the U.S. alone. This would position Fulcrum ahead of Roche, which is also developing a treatment for FSHD. Fulcrum's CEO, Alex Sapir, mentioned that losmapimod has a two- to three-year lead over Roche’s myostatin inhibitor. Other companies like Avidity and Arrowhead Pharmaceuticals are also working on potential treatments for FSHD, using antibody-oligonucleotide complexes.

The potential market for FSHD treatments is considered lucrative, partly due to the larger patient population compared to other neuromuscular diseases like Friedreich's ataxia. Fulcrum believes that losmapimod could be priced comparably to Biogen’s Skyclarys, a treatment for Friedreich's ataxia which costs $370,000 annually.

The upcoming phase 3 data will be crucial in determining whether losmapimod can achieve such a high price. Although the drug failed a phase 2b trial in FSHD in 2021, Fulcrum decided to continue development based on data suggesting the drug might slow disease progression and improve patient function. The phase 3 trial completed enrollment in September 2023, reflecting the company’s confidence in the drug’s potential.

Losmapimod has had a checkered past. Initially developed by GSK, the drug failed to demonstrate efficacy in a phase 3 trial for acute coronary syndrome and a midstage trial for chronic obstructive pulmonary disease. However, Fulcrum identified a new application for the molecule, focusing on its ability to inhibit the gene DUX4, which plays a key role in FSHD.

In acquiring the rights to losmapimod, Fulcrum compensated GSK with company stock and potential milestone payments up to $37.5 million. The development costs for the drug will be shared equally between Sanofi and Fulcrum. Fulcrum will also receive tiered royalties starting in the low-teens on annual net sales of losmapimod outside the U.S.

This collaboration between Sanofi and Fulcrum represents a significant step forward in the quest to bring a much-needed treatment to FSHD patients, potentially transforming the landscape for this rare and challenging disease.