Fulcrum Therapeutics has signed a $1bn exclusive licence deal with Sanofi to develop and commercialise the investigational facioscapulohumeral muscular dystrophy (FSHD) drug losmapimod. 

Under the agreement, Sanofi gains exclusive commercialisation rights for losmapimod outside of the US. Fulcrum will receive an upfront payment of $80m and is eligible to receive up to $975m in specified regulatory and sales-based milestones, totalling the deal value to more than $1bn. 

The drug is currently being investigated in the Phase III REACH clinical trial (NCT05397470), with topline data expected at the end of this year.  

Fulcrum exclusively in-licensed the small-molecule drug from GSK in April 2019. Losmapimod is a selective inhibitor of p38α/β mitogen-activated protein kinase (MAPK). The compound has previously been assessed for a wide variety of indications, including rheumatoid arthritis, depression, and Covid-19. 

FSHD is a genetic disorder causing progressive weakening and loss of muscle tissue. It primarily affects the muscles of the face, shoulders, and upper arms, but can also involve muscles in other body parts. The condition is caused by a mutation in the DUX4 gene, leading to the production of a protein that is toxic to muscle tissue. Preclinical studies have indicated that losmapimod demonstrated downregulation of DUX4 in patient-derived cell models and restored a healthy muscle phenotype.  

The drug was studied in the Phase IIb ReDUX4 trial (NCT04003974), which in 2021 had failed to meet its primary endpoint of change in DUX4-driven gene expression. However, the company said losmapimod was associated with potential improvements in muscle fat infiltration, and functional outcomes such as Reachable Workspace (RWS) compared to the placebo, which informed the Phase III design. The primary endpoint of the 260-patient trial is the absolute change from baseline in RWS. 

According to GlobalData’s Pharma Intelligence Center, losmapimod is forecast to generate $269m in 2030. 

GlobalData is the parent company of Pharmaceutical Technology. 

Fulcrum has other programmes in development, including the drug pociredir, previously named FTX-6058, a small-molecule inhibitor of embryonic ectoderm development (EED) for sickle cell disease. In February 2023, the US Food and Drug Administration (FDA) placed a clinical hold on the investigational drug after finding evidence of haematological malignancies in submitted preclinical data. Consequently, Fulcrum suspended dosing in the Phase Ib trial of pociredir until the FDA lifted the clinical hold in August 2023.

In the announcement accompanying the agreement, Sanofi’s global head of rare diseases Burcu Eryilmaz said: “This partnership provides an exciting opportunity to expand Sanofi’s rare disease franchise and deliver the first approved FSHD treatment to patients with the strength and reach of our commercial organisation.”