Ravulizumab (Ultomiris)

Abstract

CADTH recommends that Ultomiris should not be reimbursed by public drug plans for the treatment of adult patients with anti-acetylcholine receptor (AChR) antibody–positive generalized myasthenia gravis (gMG). Although evidence from a clinical trial (CHAMPION) suggested that Ultomiris contributed to improvement in activities of daily living and gMG disease severity after 26 weeks, it is uncertain if immunosuppressive therapy (IST) was optimized at the time of study enrolment. Patients in both Ultomiris and placebo groups of the CHAMPION trial received stable doses of IST; however, it was unclear if IST was optimized in both groups. The eligibility criteria for duration of IST treatment and duration of stable IST dosing in the CHAMPION trial were below the estimated range of time to maximal response according to the clinical experts consulted by CADTH. Although some evidence (mean time frame since MG diagnosis, mean corticosteroid treatment durations) was available, without dose information, it is unclear if corticosteroid was optimized for patients at the time of study enrolment. Feedback from patient and clinician groups identified an unmet need for patients with gMG who have symptoms but are not considered refractory to IST. There is an unmet need for effective therapy for patients with refractory gMG, but the CHAMPION trial did not require patients to be refractory. Therefore, it is unknown how many patients in the CHAMPION trial were refractory and if the results observed in the trial would be the same in these patients. As a result, the ability of Ultomiris to fill the unmet need for patients who are refractory to IST is limited by the CHAMPION trial design, which used Ultomiris earlier in the treatment paradigm for gMG and did not require participants to be refractory to IST. The CHAMPION trial did not provide evidence on the efficacy or harms of Ultomiris compared with other therapies used in clinical practice, such as rituximab, IV immunoglobulin, and plasma exchange. Therefore, the potential therapeutic benefit is unknown compared to what is used in clinical practice.