A Randomized, Double-Blind, Placebo-Controlled Study of Arimoclomol in Patients with Inclusion Body Myositis (S23.010)

Objective: To present efficacy and safety/tolerability data from phase 2/3 randomized controlled trial of arimoclomol in IBM (NCT02753530).

Background: Since immune suppression is ineffective in inclusion body myositis (IBM), modulating the cytoprotective “heat shock response” (HSR) represents a candidate therapeutic approach targeting both inflammation and degeneration. In a pilot study, arimoclomol, an amplifier of the HSR, was safe and well tolerated with some trends suggesting efficacy at 8 months in subjects with IBM.

Design/Methods: In this international multicenter, double-blind, controlled trial, subjects were randomized (1:1) to receive either arimoclomol citrate 400 mg TID or matching placebo for 20 months. Primary outcome measure was the change from baseline to Month 20 in the IBM Functional Rating Scale (IBMFRS). Key secondary outcome measures included hand grip strength (strongest hand), Modified Time Up and Go, Manual Muscle Testing, 6-minute walk distance, and Short-Form 36 health survey. Other outcome measures included patient and clinician impressions, and measures of muscle strength and function. Drug safety and tolerability were evaluated.

Results: One hundred fifty-two IBM subjects were randomized; mean age 67.2 years (SD8.1), mostly men (76%), mean disease duration 98 months (SD58), and mean baseline IBMFRS of 27.4 (SD4.6). The IBMFRS declined by a mean of 3.25 points with arimoclomol vs. 2.26 points with placebo over 20 months (p=0.11). Secondary efficacy outcome measures did not show any statistically significant treatment group differences. Most frequently reported AEs observed with higher incidence in arimoclomol group were gastrointestinal disorders. Patients receiving arimoclomol were more likely to discontinue treatment due to AEs. The relative frequency of serious AEs was comparable in the two treatment. Elevated transaminases were reported in the first three months and were more frequently observed with arimoclomol than with placebo.

Conclusions: This trial did not demonstrate a benefit of arimoclomol in IBM with respect to its primary and secondary efficacy endpoints.

Disclosure: Dr. Barohn has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for NuFactor. The institution of Dr. Barohn has received research support from FDA OPD R01. Dr. Barohn has received intellectual property interests from a discovery or technology relating to health care. Michael McDermott has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Fulcrum Therapeutics, Inc.. 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 PTC Therapeutics. The institution of Michael McDermott has received research support from NIH. The institution of Michael McDermott has received research support from Cure SMA. The institution of Michael McDermott has received research support from FDA. Dr. Lloyd has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. Dr. Shaibani has nothing to disclose. Dr. Freimer has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for argenx. Dr. Freimer has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for ra. Dr. Freimer has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for immunovant. The institution of Dr. Freimer has received research support from Amicus. The institution of Dr. Freimer has received research support from Alnylum. The institution of Dr. Freimer has received research support from Orphazyme. The institution of Dr. Freimer has received research support from catalyst. The institution of Dr. Freimer has received research support from momenta. The institution of Dr. Freimer has received research support from UCB. Dr. Amato has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Johnson & Johns. Dr. Amato has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for argenx. Dr. Amato has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurology. Dr. Amato has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for legal firms. The institution of Dr. Amato has received research support from NIH. Dr. Amato has received publishing royalties from a publication relating to health care. Dr. Ciafaloni has received personal compensation in the range of $500-$4,999 for serving as a Consultant for RaPharma, Alexion, VielaBio. 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 $10,000-$49,999 for serving on a Speakers Bureau for Biogen. 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. Dr. Mozaffar has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Alexion Pharmaceuticals. Dr. Mozaffar has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Argenx. Dr. Mozaffar has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi-Genzyme. Dr. Mozaffar has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amicus. Dr. Mozaffar has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Modis Therapeutics. Dr. Mozaffar has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for UCB/ Ra Pharmaceuticals. Dr. Mozaffar has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Maze Therapeutics. Dr. Mozaffar has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Spark Therapeutics. Dr. Mozaffar has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Acceleron. Dr. Mozaffar has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sarepta. Dr. Mozaffar has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for National Institutes of Health. Dr. Mozaffar has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Sanofi-Genzyme. Dr. Mozaffar has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Argenx. Dr. Mozaffar has received personal compensation in the range of $500-$4,999 for serving as an officer or member of the Board of Directors for Neuromuscular Disease Foundation. The institution of Dr. Mozaffar has received research support from NIH. The institution of Dr. Mozaffar has received research support from Muscular Dystrophy Association. The institution of Dr. Mozaffar has received research support from Sanofi-Genzyme. The institution of Dr. Mozaffar has received research support from Orphazyme. The institution of Dr. Mozaffar has received research support from Argenx. The institution of Dr. Mozaffar has received research support from Bristol-Myers Squibb. The institution of Dr. Mozaffar has received research support from Valerion Therapeutics. The institution of Dr. Mozaffar has received research support from Momenta. The institution of Dr. Mozaffar has received research support from Amicus Therapeutics. The institution of Dr. Mozaffar has received research support from Spark Therapeutics. The institution of Dr. Mozaffar has received research support from Audentes Therapeutics. The institution of Dr. Mozaffar has received research support from Cartesian. Dr. Mozaffar has received personal compensation in the range of $500-$4,999 for serving as a Study Section Member with NIH. Dr. Mozaffar has received personal compensation in the range of $500-$4,999 for serving as a Director, Virtual Course on Inclusion Body Myositis with Muscular Dystrophy Association. Dr. Mozaffar has received personal compensation in the range of $0-$499 for serving as a Speaker with California Neurological Association. Dr. Mozaffar has a non-compensated relationship as a Director, Annual Muscle Course with American Academy of Neurology that is relevant to AAN interests or activities. An immediate family member of Dr. Gibson has received personal compensation for serving as an employee of Recursion Pharmaceuticals. Dr. Gibson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Guidepoint. An immediate family member of Dr. Gibson has received stock or an ownership interest from Recursion Pharmaceuticals . An immediate family member of Dr. Gibson has received intellectual property interests from a discovery or technology relating to health care. Dr. Gibson has received publishing royalties from a publication relating to health care. Dr. Wicklund has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Amicus Therapeutics. Dr. Wicklund has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi-Genzyme. Dr. Wicklund has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sarepta Therapeutics. The institution of Dr. Wicklund has received research support from Orphazyme. The institution of Dr. Wicklund has received research support from Muscular Dystrophy Association. The institution of Dr. Wicklund has received research support from Coalition to Cure Calpain 3. The institution of Dr. Wicklund has received research support from Sarepta Therapeutics. The institution of Dr. Wicklund has received research support from ML Bio. The institution of Dr. Wicklund has received research support from Alexion. The institution of Dr. Wicklund has received research support from Acceleron. Dr. Levine has received personal compensation for serving as an employee of CND Life Sciences. Dr. Levine has received personal compensation for serving as an employee of Corinthian reference Labs. Dr. Levine has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Nufactor. Dr. Levine has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Grifols. Dr. Levine has received personal compensation in the range of $50,000-$99,999 for serving as an Expert Witness for PNA. Dr. Levine has received stock or an ownership interest from CND Life Sciences. Dr. Levine has received stock or an ownership interest from Corinthian reference lab. Claus Sundgreen has received personal compensation for serving as an employee of Orphazyme A/S. Karen Bonefeld has received personal compensation for serving as an employee of Orphazyme. Karen Bonefeld has received personal compensation for serving as an employee of Novo Nordisk . Mr. Joergensen has received personal compensation for serving as an employee of Orphazyme A/S. Mrs. Phonekeo has nothing to disclose. Andrew Heim has nothing to disclose. Dr. Dimachkie has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EcoR1 Capital, LLC. Dr. Dimachkie has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cello Health BioConsulting, previously Defined Health. Dr. Dimachkie has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi. Dr. Dimachkie has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for CSL Behring. Dr. Dimachkie has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Octapharma. Dr. Dimachkie has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for ArgenX. Dr. Dimachkie has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Spark Therapeutics. Dr. Dimachkie has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for RAF-5. Dr. Dimachkie has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Houston NeuroCare. Dr. Dimachkie has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Shire. Dr. Dimachkie has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Catalyst. Dr. Dimachkie has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Kezar. Dr. Dimachkie has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for RaPharma/UCB. Dr. Dimachkie has received personal compensation in the range of $500-$4,999 for serving as a Consultant for ArgenX. Dr. Dimachkie has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi. An immediate family member of Dr. Dimachkie has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Kezar. Dr. Dimachkie has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Catalyst. Dr. Dimachkie has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Takeda. Dr. Dimachkie has received personal compensation in the range of $500-$4,999 for serving as a Consultant for SCHOLAR Rock. Dr. Dimachkie has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Jenssen. Dr. Dimachkie has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amazentis. Dr. Dimachkie has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Spark Therapeutics. Dr. Dimachkie has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roivant. Dr. Dimachkie has received personal compensation in the range of $500-$4,999 for serving as a Consultant for SANEM. Dr. Dimachkie has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medlink. Dr. Dimachkie has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for CSL Behring. Dr. Dimachkie has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Third Rock. Dr. Dimachkie has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Orphazyme . Dr. Dimachkie has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Covance / Labcorp. The institution of Dr. Dimachkie has received research support from CSL Behring. The institution of Dr. Dimachkie has received research support from Orphazyme. The institution of Dr. Dimachkie has received research support from FDA-OOPD. Dr. Dimachkie has received intellectual property interests from a discovery or technology relating to health care.