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Abstract Details

Muscle Ultrasound in an Open-Label Study of Losmapimod in Subjects with FSHD1
Neuromuscular and Clinical Neurophysiology (EMG)
P5 - Poster Session 5 (11:45 AM-12:45 PM)
10-011
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.
Evaluate muscle ultrasound (US) in an open-label trial of losmapimod in FSHD1 patients.
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.
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.
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.
Nicol Voermans, MD The institution of Mrs. Voermans has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Dynacure. The institution of Mrs. Voermans has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for NIH. The institution of Mrs. Voermans has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neuromuscular disorder.
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, PhD Dr. Jiang has received personal compensation for serving as an employee of Fulcrum Therapeutics.
Jennifer Shoskes, PharmD (PepGen Inc) No disclosure on file
Kelly Marshall (Fulcrum) Ms. Marshall has nothing to disclose.
Markus Karlsson, PhD (AMRA Medical) Dr. Karlsson has received personal compensation for serving as an employee of AMRA Medical.