Directions Spring 2020

Biogen recently announced the start of recruitment for its global nusinersen clinical study, DEVOTE. The study is designed to evaluate the safety, tolerability, and potential for greater efficacy of nusinersen when administered at a higher dose than currently approved for the treatment of SMA. The Phase 2/3 randomized, controlled, dose-escalating study will be conducted at approximately 50 sites around the world and aims to enroll individuals of all ages with SMA. Scholar Rock is currently conducting the TOPAZ study to assess the safety and efficacy of SRK-015 in later-onset SMA (Type 2 and Type 3) in pediatric and adult patients. SRK-015 works by inhibiting myostatin. Myostatin is a protein that works with other proteins and hormones to help regulate muscle mass. In healthy individuals, myostatin limits muscle growth and differentiation, to prevent muscles from growing too large. For individuals affected by SMA, inhibiting this protein may combat the muscle weakness and atrophy that characterizes the disease. TOPAZ is a Phase 2 study made up of three cohorts: ambulatory Type 3 SMA; Type 2 and non-ambulatory Type 3 SMA; and Type 2 SMA and enrolled patients ages 2 to 21 years. Pre- liminary results released in November 2019 show that the drug works to increase myostatin and reported clinically significant safety findings. Trial enrollment is now complete, and the trail is currently ongoing with topline results for the 12-month treatment period expected in Q4 2020 and early 2021.

Novartis is conducting an open-label, multi-part, first-in-human study of oral branaplam in infants with Type 1 SMA. The purpose of this study is to evaluate the safety and tolerability of the drug, as well as determine appropriate dosing. Branaplamworks by increasing the amount of functional SMN protein made by the SMN2 gene. The study is no longer recruiting but is ongoing with an estimated completion in Summer 2020.

For more information about these and other SMA clinical trials, please visit www.curesma.org and www.clinicaltrials.gov.

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DIRECTIONS | SPRING 2020

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