MUSETTE Trial Confirms Optimal Dosing of Ocrelizumab for Relapsing MS

In a recent press release, Genentech has announced results from the phase 3 MUSETTE trial (NCT04544436), which evaluated higher doses of intravenous (IV) ocrelizumab (Ocrevus) in patients with relapsing multiple sclerosis (RMS). The trial failed to meet its primary endpoint, indicating that administering ocrelizumab at doses above the currently approved 600 mg does not confer additional clinical benefit in slowing disability progression. These findings suggest that the 600 mg dose remains the optimal regimen for managing RMS.

The study compared the standard 600 mg dose with a higher dose—1200 mg for patients under 75 kg and 1800 mg for those over 75 kg—administered every 6 months. The primary endpoint was time to 12-week confirmed disability progression based on a composite of functional assessments. Despite the intensified regimen, rates of disability progression were similar across all study arms and consistent with prior pivotal trials using the standard dose. Furthermore, predefined analyses showed that the 600 mg dose achieved the lowest annualized relapse rate during the double-blind period of the trial.

These results are highly consequential. Ocrelizumab, initially approved in 2017 and now available in both IV and subcutaneous formulations, remains the only anti-CD20 B-cell therapy for both RMS and primary progressive MS (PPMS). Its durability and efficacy are reaffirmed by the MUSETTE data, with relapse rates reported as low as once every 16 years. Importantly, the higher dose exhibited a similar safety profile to the 600 mg dose, with no new safety signals observed. As payers evaluate coverage decisions and optimize formularies, these results support continued prioritization of the 600 mg dose as the cost-effective, clinically validated standard of care. Full data will be shared at an upcoming medical meeting, according to Genentech’s press release.

References

McNulty R. Higher-dose ocrelizumab shows no added benefit vs approved dose in MS. AJMC. April 9, 2025. Accessed April 10, 2025. https://www.ajmc.com/view/higher-dose-ocrelizumab-shows-no-added-benefit-vs-approved-dose-in-ms

Genentech provides update on phase III Ocrevus high dose study in people with relapsing multiple sclerosis. Genentech. News release. April 2, 2025. Accessed April 10, 2025. https://www.gene.com/media/press-releases/15056/2025-04-02/genentech-provides-update-on-phase-iii-o