The long-term safety profile of nusinersen 12mg and pharmacokinetic/pharmacodynamic (PK/PD) modelling provide the basis for the DEVOTE study.

DEVOTE (NCT04089566): a 3-part, Phase 2/3 study evaluating the safety, tolerability, efficacy, and PK of nusinersen administered intrathecally at higher doses in participants with 5q SMA. Part A is an open-label safety evaluation which has enrolled 6 later-onset SMA participants who will receive 3 loading doses of 28mg at 14-day intervals followed by two 28mg maintenance doses every 4 months. After safety evaluation, Part B will enroll ≤126 participants with infantile-onset or later-onset SMA. Part B is a pivotal, double-blind, active-controlled trial with participants randomized (1:2 ratio) to receive the approved 12mg dose, or two 50mg loading doses 14 days apart with 28mg maintenance doses every 4 months thereafter. After Part B safety evaluation, Part C will enroll ~20 participants of any age/SMA type on approved nusinersen dose ≥1 year who will receive one 50mg loading dose with 28mg maintenance doses every 4 months thereafter.

The first study site was activated in Q1 2020. Updated enrollment data and Part A data will be presented. The primary objective of Part B is to evaluate the clinical efficacy of nusinersen administered at higher doses based on CHOP INTEND in infantile-onset SMA. Key endpoints include, for infantile-onset SMA: HINE-2 and event-free survival; for later-onset SMA: HFMSE, RULM, and WHO motor milestones. Secondary and exploratory objectives include examination of safety and tolerability, biomarker assessment, QoL, and PK.

The DEVOTE study has achieved Part A enrollment, with continued progress made toward an overall target enrollment of ~150 participants from ~50 centers globally.

Supported by: Biogen