Ultomiris, over months, helped majority of patients in Phase 3 trial
Clinically meaningful response seen in 86% at 6 months, 58% at about 2 weeks
More than half of adults with generalized myasthenia gravis (gMG) show a clinically meaningful response to Ultomiris (ravulizumab-cwvz) within about two weeks of a first dose, according to a post-hoc analysis of clinical trial data.
In contrast, more than 80% of these 139 trial patients experienced a meaningful reduction in disease symptoms about six months after the first dose, with regular treatment every eight weeks.
Findings suggest that “the first response to [Ultomiris] may be slower in some patients, indicating that a longer ‘trial of therapy’ may be required before it is considered ineffective,” the researchers wrote.
The study, “Time to response with ravulizumab, a long-acting terminal complement inhibitor, in adults with anti-acetylcholine receptor antibody-positive generalized myasthenia gravis,” was published in the European Journal of Neurology by an international team of scientists.
Ultomiris is approved for adults with gMG and anti-AChR antibodies
Ultomiris, marketed by Alexion, AstraZeneca Rare Disease, is a medication 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. (Two of this study’s nine scientists are Alexion employees.)
These antibodies disrupt nerve-muscle cell communication, leading to muscle weakness, a hallmark MG symptom. After an initial loading dose, the therapy is infused into the bloodstream every eight weeks.
Its U.S. approval was based on data from the placebo-controlled part of the Phase 3 CHAMPION-MG trial (NCT03920293), which enrolled 175 adults with gMG.
After 26 weeks (about six months), Ultomiris significantly outperformed a placebo in easing MG symptoms. This was assessed with the MG Activities of Daily Living (MG-ADL), a patient-reported measure of symptom severity with scores ranging from zero to 24. Higher scores indicate a greater disease impact on daily functions.
Results from the trial’s subsequent open-label extension phase, where all participants received the therapy, showed that Ultomiris was well tolerated and controlled symptoms over three years.
In this Alexion-sponsored study, researchers analyzed up to 60 weeks (a little over one year) of data from CHAMPION-MG’s Ultomiris-treated participants to assess the timing of therapeutic response.
139 people in analysis started therapy with total MG-ADL score of at least 6
The analysis population comprised 139 patients, who were treated with Ultomiris for a median of 53.7 weeks (about one year), ranging between two and 63.1 weeks, or 14 months. This group had a MG-ADL total score of six or higher at treatment start.
Based on the definition of a clinically meaningful MG-ADL response as a score drop of at least two points, results showed that 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 (about 60 weeks).
Compared with early responders (those responding at up to two weeks) and those with no clinically meaningful response, the late-responder group (those responding after more than two weeks) had a higher proportion of men and of patients with an MG crisis before entering the study. An MG crisis is a serious disease complication marked by severe muscle weakness and lung failure that requires breathing support.
The baseline (study entry) median MG-ADL score among non-responders also was lower than in the responder groups, indicating lesser disease severity before starting Ultomiris treatment.
When the researchers used a more stringent response threshold, defined by a three-point drop in MG-ADL total scores, they found that the median time to first response was 4.1 weeks after the first dose. Over time, 45% responded after two weeks, 76% after 26 weeks, and 82% at last follow-up.
Analysis supports ‘rapid onset’ of benefits with Ultomiris for most patients
Response times were assessed using Quantitative MG (QMG), a physician-reported measure of disease severity, for the 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. In total, 46% of patients responded to treatment after two weeks, 75% after 26 weeks, and 86% at last follow-up.
Early responders (four weeks or earlier) had higher pretreatment QMG scores, more patients with MG exacerbations (periods of sudden symptom worsening), and fewer patients with a MG crisis at baseline relative to late responders (response after more than four weeks) and those not meeting the response threshold.
Using a more stringent QMG response definition of a score drop of five points or more, the team found that median time to the first QMG response was 18.3 weeks, or about four months, after the first dose. Here, response rates were 26% after two weeks, 52% after 26 weeks, and 59% at last follow-up.
“A considerable proportion of patients had a first response within 2 weeks of initiating [Ultomiris] treatment, even when assessed using thresholds above [minimal clinically important differences],” the researchers wrote.
“This represents an important potential clinical benefit for patients; in particular, the rapid onset of improvement in the MG-ADL score with [Ultomiris] treatment reflects the ability to quickly recover function in routine daily activities, from the patient’s perspective,” they added.
Data also demonstrate that in clinical practice “a longer than anticipated [Ultomiris] treatment trial may be warranted for some patients before considering treatment discontinuation,” the team wrote. “Further work to evaluate patient and disease characteristics that predict response and timing of response would be beneficial.”
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