Objective:

Evaluate muscle ultrasound (US) in an open-label trial of losmapimod in FSHD1 patients.

Background:

Natural history studies have identified US as a viable imaging biomarker for FSHD muscle progression, complementary to MRI. Losmapimod is an orally active, selective, small molecule inhibitor of p38α/β.

Design/Methods:

Fourteen subjects ages 18 to 65 years with genetically confirmed FSHD1, clinical severity score 2 to 4 (range 0-5) and MRI-eligible skeletal muscles for needle biopsy received open-label 15 mg twice daily losmapimod for 52 weeks with the primary objective of safety. Assessments included safety, MRI, US, clinical outcomes, and Patient Reported Outcomes. US was performed on 7 muscles bilaterally using a standardized protocol. US echointensity was expressed as a z-score relative to matched healthy controls, with abnormal being defined as >2.

Results:

The mean (SD) change from baseline in echogenicity of all muscles was -0.17 (0.9), in the upper extremity muscles -0.32 (0.9) and lower extremities -0.13 (1.0), represented a trend towards improvement. The distribution of muscle z-scores (<2, 2-4, 4-6, and >6) at baseline and after 52 weeks of treatment remained the same. Echointensity correlated strongly with MFI for the biceps brachii (r=0.84, p<0.01), tibialis anterior (r=0.76, p<0.01), and gastrocnemius medialis (r=0.50, p<0.01). Correlations between US and clinical outcomes will be presented.

Conclusions:

Losmapimod demonstrated stability in muscle US over 52 weeks.