Abstract Details

Title Muscle Ultrasound in an Open-Label Study of Losmapimod in Subjects with FSHD1

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) P5 - Poster Session 5 (11:45 AM-12:45 PM)

Poster/Presentation
Number 10-011

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.

Authors/Disclosures
Joost Kools, MD (Radboudumc) PRESENTER	The institution of Mr. Kools has received research support from Fulcrum Therapeutics.
	No disclosure on file
Karlien Mul	The institution of Karlien Mul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Avidity Biosciences.
John Jiang	No disclosure on file
Jennifer Shoskes, PharmD (PepGen Inc)	No disclosure on file
	No disclosure on file
	No disclosure on file

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