The first individual has been treated in the global clinical study, DEVOTE (NCT04089566). The study is designed to evaluate the safety, tolerability, and potential for even greater efficacy of nusinersen (Spinraza; Biogen, Research Triangle Park, NC) when administered at a higher dose than currently approved for the treatment of spinal muscular atrophy (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.
“Today, people of all ages with SMA are achieving better outcomes related to survival, mobility and independence, yet there is still no cure and unmet needs remain for many,” said Kenneth Hobby, president of Cure SMA, a patient advocacy organization dedicated to the treatment and cure of SMA. “Our community is energized by the advances we’ve made and believes that ongoing research like the DEVOTE study is instrumental to help deepen our understanding and potentially further transform and improve what it means to live with SMA.”
The 3-part study will include an open-label safety evaluation cohort and a pivotal double-blind, active control randomized treatment cohort followed by an open-label treatment cohort. After the safety evaluation cohort completes, the pivotal cohort will begin and include a treatment group receiving 2 loading doses of 50 mg 14 days apart, followed by a maintenance dose of 28 mg every 4 months. A second treatment group will receive the current US Food and Drug Administration (FDA)-approved administration of nusinersen, which is 4 loading doses with 12-mg maintenance doses every 4 months. The third cohort will be an open-label evaluation to assess the safety and tolerability of transitioning patients from the currently approved dose of nusinersen to the higher dose being tested in the study.
“As the first treatment for SMA, Spinraza fundamentally shifted the disease course compared to natural history, allowing many individuals to reach milestones that may have been previously unattainable,” said Alfred Sandrock Jr., MD, PhD, executive vice president, Research and Development at Biogen. “With the success we’ve seen to date with the 12-mg dose, we are exploring a higher dose of Spinraza for the potential to deliver even better clinical outcomes.”
Vanessa Baute Penry, MD; Rachana Gandhi Mehta, MD; and Fatemeh Sadeghifar, BS
Melissa W. Ko, MD; Kevin E. Lai, MD; and Devin D. Mackay, MD