Abstract Details

Title Nusinersen Efficacy in Adults with Spinal Muscular Atrophy

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) S58 - Therapeutics in Neuromuscular Disorders (2:06 PM-2:17 PM)

Poster/Presentation
Number 007

Background SMA is an autosomal recessive disorder affecting 1:10,000 live births, in which survival motor neuron (SMN) protein deficiency leads to motor neuron degeneration and progressive muscle atrophy, weakness, and early mortality. In December, 2016, nusinersen was approved by the FDA for SMA patients of all ages despite the lack of documented efficacy in adults

Objective To determine the clinical effects of nusinersen in adults with spinal muscular atrophy (SMA) during the first two years of commercial availability, in comparison to the natural history of untreated adults.

Design/Methods Outcome measures were collected prospectively on treatment-naive adult SMA patients followed in the Pediatric Neuromuscular Clinical Research (PNCR) Network and compared with a separate group of adults with SMA who were assessed before and after starting nusinersen. A minimal data set based on insurance requirements and validated SMA outcomes included: RULM, HFMSE, TUG, 6MWT, jaw ROM, and the CHOP-Intend neuromuscular scale that was revised for severely affected adults (CHOP-ATEND). Pulmonary function, strength and HHD, patient reported experiences, safety labs and adverse events also were monitored.

Results

Results: Natural history was determined in 99 untreated adults and response to nusinersen in 34 adults. More than 90% of patients reported qualitative improvement in: strength, stamina, breathing strength, chewing/swallowing, jaw range of motion, voice strength, or muscle strength. Patients were assigned to one of three functional groups: ambulatory, non-ambulatory strong (RULM > 4), and non-ambulatory weak (RULM ≤ 4); primary functional measures in the groups were 6MWT, RULM, and CHOP-ATEND respectively. Additionally, MIP, MEP and FVC and HHD were monitored in all groups. All measures showed improvement in the treated groups compared to the progressive decline seen in untreated adults.

Conclusions Nusinersen has been well tolerated. Improvement trends are emerging at all disability levels by multiple outcome measures, demonstrating nusinersen efficacy for adults with SMA.

Authors/Disclosures
John W. Day, MD, PhD (Stanford University School of Medicine) PRESENTER	Dr. Day has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis Gene Therapy. Dr. Day has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Day has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche/Genentech. Dr. Day 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. Day has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Avidity. Dr. Day has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for PepGen. Dr. Day has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Epirium Bio. Dr. Day has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Solid Biosciences. Dr. Day has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Muscular Dystrophy Association. The institution of Dr. Day has received research support from Astellas Pharma. The institution of Dr. Day has received research support from Novartis Gene Therapy. The institution of Dr. Day has received research support from Biogen. The institution of Dr. Day has received research support from Roche/Genentech. The institution of Dr. Day has received research support from Sanofi/Genzyme. The institution of Dr. Day has received research support from Sarepta. The institution of Dr. Day has received research support from Scholar Rock. The institution of Dr. Day has received research support from AMO Pharma. The institution of Dr. Day has received research support from AnnJi. Dr. Day has received research support from CureSMA. The institution of Dr. Day has received research support from Muscular Dystrophy Association. The institution of Dr. Day has received research support from Ionis Pharmaceuticals. The institution of Dr. Day has received research support from NMD Pharma. The institution of Dr. Day has received research support from SMA Foundation. Dr. Day has received intellectual property interests from a discovery or technology relating to health care.
Connie Wolford, NP (Stanford Healthcare)	Ms. Wolford has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen.
	No disclosure on file
William Martens (University of Rochester)	William Martens has nothing to disclose.
Michael McDermott	No disclosure on file
Basil T. Darras, MD (Children'S Hosp Boston Harvard Med School)	The institution of Dr. Darras has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amicus. Dr. Darras has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Amicus. The institution of Dr. Darras has received research support from National Institutes of Health/National Institute of Neurological Disorders and Stroke,. The institution of Dr. Darras has received research support from Slaney Family Fund for SMA. The institution of Dr. Darras has received research support from Spinal Muscular Atrophy Foundation. The institution of Dr. Darras has received research support from CureSMA. The institution of Dr. Darras has received research support from Working on Walking Fund . The institution of Dr. Darras has received research support from CHERISH, CS2/CS12 . The institution of Dr. Darras has received research support from Biogen for CS11. The institution of Dr. Darras has received research support from AveXis. The institution of Dr. Darras has received research support from Sarepta Pharmaceuticals. The institution of Dr. Darras has received research support from PTC Therapeutics. The institution of Dr. Darras has received research support from Roche. The institution of Dr. Darras has received research support from Santhera. The institution of Dr. Darras has received research support from Scholar Rock. The institution of Dr. Darras has received research support from Fibrogen. The institution of Dr. Darras has received research support from Summit. Dr. Darras has received publishing royalties from a publication relating to health care. Dr. Darras has received publishing royalties from a publication relating to health care.
	No disclosure on file
Zarazuela Zolkipli-Cunningham, MBChB (The Children's Hospital of Philadelphia, Human Genetics)	Dr. Zolkipli-Cunningham has nothing to disclose.
Richard S. Finkel, MD, FAAN (St. Jude Children's Research Hospital)	Dr. Finkel has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for AveXis. Dr. Finkel has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Finkel has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Catabasis. Dr. Finkel has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Capricor. Dr. Finkel has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for ReveraGen. Dr. Finkel has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Finkel 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. Finkel 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. The institution of Dr. Finkel has received research support from AveXis. The institution of Dr. Finkel has received research support from Biogen. The institution of Dr. Finkel has received research support from Capricor. The institution of Dr. Finkel has received research support from Catabasis. The institution of Dr. Finkel has received research support from ReveraGen. The institution of Dr. Finkel has received research support from Roche. The institution of Dr. Finkel has received research support from Scholar Rock. Dr. Finkel has received intellectual property interests from a discovery or technology relating to health care. An immediate family member of Dr. Finkel has received intellectual property interests from a discovery or technology relating to health care. Dr. Finkel has received personal compensation in the range of $0-$499 for serving as a Speaker in workshop with National Academy of Sciences. Dr. Finkel has a non-compensated relationship as a advisor with n-Lorem Foundation that is relevant to AAN interests or activities. Dr. Finkel has a non-compensated relationship as a Board Member with EveryLife Foundation that is relevant to AAN interests or activities.
	No disclosure on file
Jacinda B. Sampson, MD, PhD	Dr. Sampson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Dyne Therapeutics. Dr. Sampson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Viking Therapeutics. Dr. Sampson has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Dr. Sampson has received research support from Marigold Foundation. Dr. Sampson has a non-compensated relationship as a Scientific Advisory Committee with Myotonic Dystrophy Foundation that is relevant to AAN interests or activities.
	No disclosure on file
Tina Duong	Tina Duong has received personal compensation for serving as an employee of Roche. Tina Duong has received personal compensation for serving as an employee of Novartis. Tina Duong has received personal compensation for serving as an employee of Scholar Rock. Tina Duong has received personal compensation for serving as an employee of Genentech. Tina Duong has received personal compensation for serving as an employee of Novartis. Tina Duong has received personal compensation for serving as an employee of Sarepta. Tina Duong has received personal compensation for serving as an employee of Biogen. Tina Duong has received personal compensation for serving as an employee of Audentes. Tina Duong has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Tina Duong has received personal compensation in the range of $0-$499 for serving as a Consultant for Audentes. Tina Duong has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Tina Duong has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Tina Duong has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Tina Duong has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Tina Duong has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Genentech. Tina Duong has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sarepta. Tina Duong has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for biogen. The institution of Tina Duong has received research support from biogen. The institution of Tina Duong has received research support from scholar rock.

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