High-Dose Nusinersen Trial Reports Motor-Function Gains In SMA

In the DEVOTE trial, researchers reported that among Part B infantile-onset participants, CHOP-INTEND total scores improved at day 183 with high-dose nusinersen compared with matched ENDEAR sham participants. DEVOTE was a global, three-part, phase 2/3 program evaluating nusinersen across several trial settings in individuals with spinal muscular atrophy. Investigators assessed efficacy and safety for a regimen using a 50-mg loading dose followed by 28-mg maintenance dosing.

Part B was described as the randomized portion for treatment-naive participants, with 75 individuals assigned in a 2:1 ratio to 50/28 mg or standard 12/12 mg nusinersen. Part C was outlined as a supportive open-label cohort for participants who had received 12/12 mg nusinersen for more than 1 year before entry. These groups were included within the same higher-dose development program, while differing in treatment history at baseline. Part C was presented as supportive data rather than a randomized comparison.

For infantile-onset participants, the abstract reported a primary endpoint comparing 6-month change in CHOP-INTEND at day 183 for 50/28 mg nusinersen versus matched ENDEAR participants who received sham. The authors reported that CHOP-INTEND improved by 15.1 points in the 50/28 mg group, while matched ENDEAR participants declined by 11.1 points. They also reported a difference in ranks of 26.06 (95% CI, 17.9 to 34.2; P<0.0001) for that comparison. This analysis focused on infantile-onset participants within Part B and used matched ENDEAR sham participants (n=20) rather than the broader enrolled population. On that basis, researchers concluded that the primary motor-function endpoint was met.

Investigators reported that the safety profile of 50/28 mg nusinersen was similar to the 12/12 mg regimen. The reported data did not provide specific adverse events or a fuller safety breakdown, and no additional numerical safety results were summarized beyond the statement of similarity. In the abstract, the authors concluded that the data support benefit with a generally well-tolerated safety profile for the higher-dose regimen in spinal muscular atrophy.

Key Takeaways

• DEVOTE evaluated a 50/28 mg nusinersen regimen in a global, three-part trial that included randomized treatment-naive participants.
• Researchers reported a positive CHOP-INTEND motor-function result at day 183 in infantile-onset participants.
• Safety was described as similar to standard dosing, and the investigators concluded the regimen was generally well tolerated.