Ultomiris (ravulizumab-cwvz) demonstrates a clinically meaningful response in more than half of adults with generalized myasthenia gravis (gMG) within approximately two weeks of the first dose, according to a post-hoc analysis of the CHAMPION-MG clinical trial data. However, the study also revealed that over 80% of patients experienced a more significant reduction in disease symptoms after about six months of treatment with regular infusions every eight weeks, suggesting that some patients may require a longer trial period to experience the full benefits of the therapy.
The findings, published in the European Journal of Neurology, indicate that the initial response to Ultomiris may be slower in some patients, suggesting that a longer trial of therapy may be required before considering it ineffective. The research team, including scientists from Alexion, AstraZeneca Rare Disease, analyzed data from the CHAMPION-MG trial to assess the timing of therapeutic response in Ultomiris-treated participants.
Ultomiris for gMG with Anti-AChR Antibodies
Ultomiris, marketed by Alexion, AstraZeneca Rare Disease, is approved in the U.S. for adults with gMG who have self-reactive antibodies against the acetylcholine receptor (AChR), the most common cause of MG. These antibodies disrupt nerve-muscle cell communication, leading to muscle weakness, a hallmark MG symptom. The therapy is administered intravenously every eight weeks after an initial loading dose.
The U.S. approval was based on data from the placebo-controlled Phase 3 CHAMPION-MG trial (NCT03920293), which enrolled 175 adults with gMG. After 26 weeks, Ultomiris significantly outperformed placebo in easing MG symptoms, as assessed by the MG Activities of Daily Living (MG-ADL) scale. Higher scores on the MG-ADL indicate a greater disease impact on daily functions.
Results from the trial’s open-label extension phase demonstrated that Ultomiris was well-tolerated and controlled symptoms over three years.
Timing of Therapeutic Response
The analysis population comprised 139 patients treated with Ultomiris for a median of 53.7 weeks, with a MG-ADL total score of six or higher at treatment start. Based on a clinically meaningful MG-ADL response defined as a score drop of at least two points, patients responded after a median of 2.1 weeks after the first dose. Over time, 58% showed a response after two weeks, 86% after 26 weeks, and 88% at last follow-up.
When using a more stringent response threshold, defined by a three-point drop in MG-ADL total scores, the median time to first response was 4.1 weeks after the first dose. Response rates were 45% after two weeks, 76% after 26 weeks, and 82% at last follow-up.
Quantitative MG (QMG) Assessment
Response times were also assessed using Quantitative MG (QMG), a physician-reported measure of disease severity, for 134 patients with available data. The time to the first QMG response, defined as a score drop of three or more points, was 4.1 weeks after the first dose. Overall, 46% of patients responded to treatment after two weeks, 75% after 26 weeks, and 86% at last follow-up.
Using a more stringent QMG response definition of a score drop of five points or more, the median time to the first QMG response was 18.3 weeks after the first dose, with response rates of 26% after two weeks, 52% after 26 weeks, and 59% at last follow-up.
Clinical Implications
The researchers emphasized the potential clinical benefit of Ultomiris, noting that a considerable proportion of patients experienced a first response within two weeks of initiating treatment. They also highlighted that a longer than anticipated treatment trial may be warranted for some patients before considering treatment discontinuation. Further research is needed to evaluate patient and disease characteristics that predict response and timing of response, which could help optimize treatment strategies.
