Sanofi Pays $80 Million Upfront to Partner with Fulcrum Therapeutics on Losmapimod for FSHD

May 13,Fulcrum Therapeutics ("Fulcrum") announced a collaboration and licensing agreement with Sanofi for the development and commercialization rights of the investigational new drug Losmapimod.。

According to the terms of the agreement,Sanofi Obtains Exclusive Commercialization Rights for Losmapimod in All Regions Outside the United States. Fulcrum Retains Full Commercialization Rights for Losmapimod in the United States and Will Receive an Upfront Payment of $80 Million (approximately 580 million RMB), While Being Eligible for Potential Milestone Payments of $975 Million., as well as tiered royalties on sales of the drug outside the United States. The two parties will collaborate globally to develop Losmapimod and equally share future development costs.

Facioscapulohumeral Muscular Dystrophy (FSHD) is a hereditary rare disease that primarily affects the face, shoulders, and upper arms, characterized by muscle weakness and atrophy. It is the second most common type of muscular dystrophy. FSHD generally manifests in adolescence, and as the disease progresses, it may spread to the abdominal and gluteal muscles. Approximately 20% of patients lose the ability to walk before the age of 50, significantly impacting their daily living activities.

In FSHD patients, about 95% of cases are caused by variations in chromosome 4, leading to abnormal expression of the DUX4 gene. Currently, there are no approved treatments available. According to data from the FSH Society in the United States, there are approximately 870,000 FSHD patients worldwide.

Losmapimod is a selective p38α/β mitogen-activated protein kinase (MAPK) inhibitor designed to reduce DUX4 activity by blocking the p38α and p38β proteins.Losmapimod was initially developed by GSK. In 2019, Fulcrum Therapeutics entered into an exclusive global licensing agreement with GSK, obtaining the global development and commercialization rights for the drug.

Losmapimod cell test data shows that Losmapimod can effectively inhibit the expression of DUX4. Previously,Losmapimod has received Fast Track designation and Orphan Drug designation from the FDA for the treatment of FSHD.。

On May 8, Fulcrum published the results of the Phase 2b clinical trial (ReDUX4) of Losmapimod for the treatment of FSHD in The Lancet Neurology. The trial aimed to evaluate the safety and efficacy of Losmapimod in treating FSHD. The trial enrolled 80 patients aged 18-65 with type 1 FSHD who were identified through genotyping as having lost suppression of DUX4 expression. Patients were randomly assigned to receive either 15mg of Losmapimod orally or a placebo twice daily for 48 weeks.

The results showed that Losmapimod has the potential to slow disease progression and improve upper limb function, with good tolerability. No serious adverse events related to the drug were reported during the trial, and no treatment was interrupted due to adverse events.

Currently, Losmapimod is continuing to be evaluated for its efficacy and safety in treating FSHD in a Phase 3 REACH trial. In September last year, Fulcrum announced that patient enrollment for the REACH trial had been completed.Fulcrum Therapeutics expects to release top-line data from the REACH trial in the fourth quarter of 2024. Based on positive data from the Phase 3 clinical trial, Fulcrum and Sanofi plan to submit marketing applications in the United States, Europe, Japan, and other regions.。

Fulcrum Therapeutics President and CEO Alex C. Sapir said in a press release, "Losmapimod has demonstrated meaningful clinical benefits and potential for treating FSHD. Compared with other candidate drugs under development, Losmapimod has a 3-4 year lead and is expected to become the first approved treatment for FSHD.”。

Fulcrum is not Sanofi's first partner in the FSHD drug development field.

In 2022,Sanofi Enters into Strategic Collaboration and Exclusive License Agreement with miReculeAccording to the terms of the agreement, miRecule granted Sanofi the global exclusive license rights to FSHD therapy—MC-DX4, while miRecule received a $30 million upfront payment and potential milestone payments of up to $400 million. MC-DX4 is an anti-DUX4 RNA therapy (ARC) that can prevent disease progression by knocking down the DUX4 gene in muscle tissue. However,MC-DX4 is still in preclinical research, and its progress is far behind that of Losmapimod.。

Since acquiring orphan drug giant Genzyme for $20.1 billion in 2011, Sanofi has continuously strengthened its position in the rare disease drug market, maintaining an absolute leadership role. However,Currently, Sanofi's dominant position is being challenged, one of which is the expiration of product patents, facing the impact of generic drugs.For example, Aubagio, a treatment for multiple sclerosis, was once Sanofi's flagship product, with sales second only to Dupixent, the flu vaccine, and Lantus. However, following the expiration of its patent in 2023, Aubagio's sales in 2023 dropped by 52.6% year-on-year.To strengthen its position in the rare disease market, Sanofi has been taking frequent actions, introducing new candidate pipelines in the hope of finding products with more differentiated advantages.According to incomplete statistics from the PharmaCube database, Sanofi has been involved in 20 licensing-in deals in the rare disease field over the past five years, with a total transaction value exceeding 12.5 billion US dollars.

In May last year, Sanofi announced a cooperation agreement with Maze Therapeutics ("Maze"). Sanofi will obtain the development and commercialization rights of Maze's Pompe disease candidate drug MZE001, with an upfront payment of 150 million US dollars and milestone payments of 600 million US dollars.

However, this collaboration was considered by the U.S. Federal Trade Commission (FTC) as an act of monopolizing the Pompe disease treatment market. Nate Soderstrom, Acting Deputy Director of the FTC’s Bureau of Competition, stated that Sanofi's acquisition of Maze's Pompe disease candidate drug MZE001 could deprive patients of the opportunity to access new and innovative treatments.In December 2023, Sanofi announced the termination of its collaboration and licensing agreement with Maze.。

Despite the forced termination of its collaboration with Maze, this did not affect Sanofi's speed in making moves within the rare disease field.In January this year, Sanofi announced that it had entered into a definitive agreement with Nhibrx. According to the agreement, Sanofi's subsidiary Aventis in Pennsylvania will acquire all assets and liabilities related to INBRX-101.INBRX-101 is a rare disease therapy used to treat emphysema patients caused by Alpha-1 Antitrypsin Deficiency (AATD). The acquisition of INBRX-101 further expands Sanofi's presence in the rare disease field.

Currently, Sanofi has 11 pipelines in the rare disease field under research, with six candidate products in Phase 3 clinical trials. In 2023, Sanofi's revenue was approximately $47.097 billion, representing a year-on-year increase of 5.3%.From the perspective of sales composition, products in the rare disease field have become one of its main sources of revenue.Among them, three rare disease products—Nexviazyme/Nexviadzyme, Enjaymo, and Xenpozyme—have performed remarkably well, all maintaining growth rates exceeding 100%. However, in terms of sales growth, although Enjaymo and Xenpozyme have shown strong performance, their respective sales have yet to break the $100 million mark, making it difficult to offset the gap caused by the decline in Aubagio's sales in the short term.

Besides, in the revenue of 47.97 billion US dollars, Dupixent (dupilumab) sales reached about 11.58 billion US dollars, accounting for about one-fourth of Sanofi's income in 2023. However, over-reliance and heavy pressure on a single product may bring development risks to Sanofi. Therefore, Sanofi is undergoing reorganization optimization to raise funds and accelerate the layout in the fields of rare diseases and autoimmune diseases, in order to find the next blockbuster product with differentiated advantages.