Sanofi Secures Ex-U.S. Rights to Phase 3 p38α/β MAPK Inhibitor Losmapimod in $1.055 Billion Deal

About Losmapimod

Losmapimod is a selective p38α/β mitogen-activated protein kinase (MAPK) inhibitor designed to reduce the activity of the DUX4 gene by blocking the p38α and p38β proteins.In FSHD,About 95% of patients are caused by variations in chromosome 4, leading to abnormal expression of the DUX4 gene.。

LosmapimodOriginally developed by GlaxoSmithKline ("GSK"), in April 2019, Fulcrum Therapeutics acquired all rights to losmapimod from GSK. The drug has received FDA Fast Track designation and orphan drug designation for the treatment of FSHD, and is currently being evaluated in a Phase 3 multicenter, randomized, double-blind, placebo-controlled, 48-week parallel group study in patients with FSHD.

The Phase 2 ReDUX4 trial aimed to evaluate the safety and efficacy of losmapimod in treating FSHD. The trial enrolled adults aged 18-65 with type 1 FSHD who had genetically confirmed loss of DUX4 expression suppression, a Ricci clinical severity score of 2-4, and at least one skeletal muscle deemed suitable for biopsy by MRI. Participants were randomly assigned (1:1) to receive either oral losmapimod (15 mg twice daily) or a matching placebo for 48 weeks. The primary endpoint was the change in DUX4-driven gene expression in skeletal muscle biopsy samples from baseline to week 16 or week 36, as determined by quantitative RT-PCR; secondary endpoints included assessments of safety and tolerability.

The results showed that although the primary endpoint of DUX4-driven gene expression changes in muscle biopsies did not demonstrate a significant difference between the treatment and placebo groups, losmapimod was associated with improvements in structural and functional outcomes. These include muscle fat infiltration, accessible work area (a measure of shoulder girdle function), and patient-reported overall change impression compared to placebo.

In addition, losmapimod was well tolerated, with no serious adverse events related to the drug reported and no treatment interruptions due to adverse events.

About FSHD

FSHD is a hereditary, progressive atrophy disease commonly affecting the facial, scapular, and upper arm muscles. It is the second most common muscular dystrophy and currently has no approved therapies. FSHD patients typically experience weakness and atrophy of the eye, mouth, shoulder, upper arm, and calf muscles before the age of 20; as the condition worsens, FSHD may spread to the abdominal and gluteal muscles, with about 20% of patients requiring wheelchair mobility before the age of 50.

FSHD progresses slowly and is not fatal, but it can significantly impact patients' quality of life—some may even require ventilators to assist with normal living. The FSH Society in the U.S. estimates that approximately 870,000 people worldwide are affected by this condition.

About Sanofi's Layout in FSHD

In October 2022, Sanofi entered into a collaboration and exclusive licensing agreement with biotechnology company miRecule to develop and commercialize a novel antibody-RNA conjugate (ARC) for the treatment of FSHD. Under the terms of the collaboration agreement, Sanofi will obtain a global exclusive license for the novel FSHD therapy, while miRecule will initially receive an upfront payment of approximately $30 million, with potential future milestone payments totaling close to $400 million as well as tiered royalties.

miRecule's proprietary, genome-based DREAmiR discovery platform is capable of identifying key RNA targets for the development of drugs tailored to specific patient populations. miRecule’s proprietary RNA therapies exhibit improved pharmacological properties and can be conjugated with antibodies for targeted tissue delivery. For instance, the company’s lead program, MC-30, aims to replace microRNA-30 (miRNA-30), which has tumor-suppressing activity in head and neck cancer; approximately half of these patients lose miRNA-30 expression. Another project isRNA TherapyMC-DX4, which can eliminate the expression of the DUX4 gene in FSHD patients.