Results from a 36-Week Open-Label Study of Recombinant Human Growth Hormone and Testosterone in Facioscapulohumeral Muscular Dystrophy (FSHD) (S48.009)

Objective: To determine the safety and tolerability of daily recombinant human growth hormone (rHGH) combined with testosterone injections every 2 weeks in ambulatory men with FSHD. Background: FSHD is a progressive muscular dystrophy that affects ~4/100,000 people globally. Clinically, FSHD causes progressive weakness, muscle atrophy, and limitations with ambulation. A treatment that limits disease progression and/or reverses functional decline would be beneficial to this population. Design/Methods: We conducted a single center (University of Rochester), single-arm, proof-of-concept study to evaluate the safety and tolerability of daily rHGH (Genotropin®) combined with testosterone enanthate injections every 2 weeks in men with FSHD. Participants received study drugs for 24 weeks followed by a 12-week washout period. Participants received serial safety testing, laboratory testing, functional assessments, and disease burden monitoring during the study. Results: Nineteen out of 20 participants completed the study, with no participants experiencing a serious adverse event. One participant dropped out due to travel distance and the COVID pandemic. The most common adverse event was soreness at the rHGH/testosterone injection site (6 participants). After 24 weeks, the six-minute walk distance increased by 37.3 meters (p=0.0007), lean body mass improved by 2.2 kg (p<0.0001), body fat reduced by 1.3 kg (p=0.04), overall strength (standardized QMT, average % of predicted normal) increased by 3% (p=0.03), and total disease burden (FSHD-HI) reduced by 19% (6 points; p=0.04) from baseline. Conclusions: Combination therapy is safe and well-tolerated in men with FSHD. Despite FSHD being a progressive disease, participants experienced improvements in ambulation, strength, muscle mass, and disease burden in response to this study intervention. Placebo-controlled trials are needed to further investigate this promising therapeutic approach. Disclosure: Dr. Heatwole has received personal compensation for serving as an employee of Legal Med. Dr. Heatwole has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Virginia Commonwealth University. Dr. Heatwole has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Harmony. Dr. Heatwole has received personal compensation in the range of $500-$4,999 for serving as a Consultant for IRIS. Dr. Heatwole has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Recursion. Dr. Heatwole has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Avidity. Dr. Heatwole has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Takeda. Dr. Heatwole has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Pennsylvania Prop and Gas Ins. Dr. Heatwole has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Harmony. Dr. Heatwole has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for cytokinetics. Dr. Heatwole has received personal compensation in the range of $500-$4,999 for serving as a Consultant for scholar rock. Dr. Heatwole has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for neurocrine. Dr. Heatwole has received personal compensation in the range of $500-$4,999 for serving as a Consultant for swan bio. Dr. Heatwole has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Scholar Rock. Dr. Heatwole has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Legal Med. The institution of Dr. Heatwole has received research support from NIH. The institution of Dr. Heatwole has received research support from Recursion. The institution of Dr. Heatwole has received research support from MDA. The institution of Dr. Heatwole has received research support from PPMD. The institution of Dr. Heatwole has received research support from FARA. The institution of Dr. Heatwole has received research support from Curesma. The institution of Dr. Heatwole has received research support from ALSA. The institution of Dr. Heatwole has received research support from Huntington Study Group. The institution of Dr. Heatwole has received research support from department of defence. The institution of Dr. Heatwole has received research support from swan bio. The institution of Dr. Heatwole has received research support from Parent project. Dr. Heatwole has received intellectual property interests from a discovery or technology relating to health care. Elizabeth Luebbe has nothing to disclose. Dr. Hamel has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Vertex Pharmaceuticals. Dr. Mongiovi has nothing to disclose. Dr. Ciafaloni has received personal compensation in the range of $500-$4,999 for serving as a Consultant for RaPharma, Alexion, VielaBio,Sarepta,Biogen. Dr. Ciafaloni has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sarepta and AVEXIS. Dr. Ciafaloni has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Medlink. The institution of Dr. Ciafaloni has received research support from CDC, MDA, CureSMA, FDA, Orphazyme, Sarepta, Santhera, PCORI. Dr. Ciafaloni has received publishing royalties from a publication relating to health care. Nuran Dilek has nothing to disclose. William Martens has nothing to disclose. Dr. Weber has received personal compensation in the range of $500-$4,999 for serving as a Consultant for PTC Therapeutics. The institution of Dr. Weber has received research support from Inozyme. Dr. Rashid has nothing to disclose. Mrs. Allen has nothing to disclose. Miss Smith has nothing to disclose. Miss Howell has nothing to disclose. The institution of Prof. Rosero has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biotronik. The institution of Prof. Rosero has received research support from Medtronic . Prof. Rosero has received intellectual property interests from a discovery or technology relating to health care. Ms. Eichinger has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Fulcrum. Ms. Eichinger has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Avidity. Ms. Eichinger has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for DyneTherapeutic. Ms. Eichinger has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Ms. Eichinger has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for FSHD Society. The institution of Ms. Eichinger has received research support from Charcot Marie Tooth Association. Mrs. Baker has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Jeanne Dekdebrun has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Avidity Biosciences. Mr. Hilbert has nothing to disclose. Miss Varma has nothing to disclose. Michael McDermott has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for NeuroDerm, Ltd.. Michael McDermott has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eli Lilly and Company. Michael McDermott has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Catabasis Pharmaceuticals, Inc.. Michael McDermott has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Vaccinex, Inc.. Michael McDermott has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Neurocrine Biosciences, Inc.. Michael McDermott has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Prilenia Therapeutics Development, Inc.. Michael McDermott has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for ReveraGen BioPharma, Inc.. Michael McDermott has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for NS Pharma, Inc.. The institution of Michael McDermott has received research support from NIH. The institution of Michael McDermott has received research support from FDA. The institution of Michael McDermott has received research support from Cure SMA. Dr. Thornton has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Avidity. Dr. Thornton has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Thornton has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Ionis. Dr. Thornton has received personal compensation in the range of $50,000-$99,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Dyne. Dr. Thornton has received personal compensation in the range of $50,000-$99,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Pepgen. The institution of Dr. Thornton has received research support from Marigold Foundation. The institution of Dr. Thornton has received research support from NIH. The institution of Dr. Thornton has received research support from Muscular Dystrophy Association . The institution of Dr. Thornton has received research support from Dyne. The institution of Dr. Thornton has received research support from Avidity. The institution of Dr. Thornton has received research support from Ionis. Dr. Thornton has received intellectual property interests from a discovery or technology relating to health care. Richard Moxley has nothing to disclose.