AAN 2023: Ultomiris posts favorable clinical responses in trial analyses
Conference presentations examine Phase 3 CHAMPION MG clinical trial results
More generalized myasthenia gravis (gMG) patients who received Ultomiris (ravulizumab) in the Phase 3 CHAMPION MG trial achieved a favorable clinical response to treatment relative to those taking a placebo, according to new trial analyses.
The proportion of patients achieving that milestone, according to the Myasthenia Gravis Foundation of America Post-Intervention Status (MGFA-PIS), was sustained and further increased during the trial’s open-label extension (OLE) period.
The new data were presented by Srikanth Muppidi, MD, of Stanford University School of Medicine, California, at the American Academy of Neurology (AAN) 2023 Annual Meeting, held April 22-27 in Boston, Massachusetts, and virtually.
Additional trial analyses, presented in a pair of posters at the AAN meeting, indicated that patients began seeing a clinically meaningful reduction in gMG symptoms a median of a month after starting treatment, and that treatment responses were similar in patients who had or had not been on intravenous immunoglobulin (IVIg) therapy previously.
CHAMPION MG (NCT03920293) enrolled 175 gMG patients positive for acetylcholine receptor (AChR) antibodies, who were assigned randomly to receive into-the-vein Ultomiris or a placebo for about six months. Most participants then opted to enter in the study’s OLE, where all are being treated with Ultomiris for up to four years.
The main trial met its goal of significantly easing gMG symptoms relative to placebo, as assessed by the MG Activities of Daily Living (MG-ADL) scale, a patient-reported measure of symptom severity. This was sustained for up to 60 weeks (more than a year) across the trial and OLE.
At the AAN meeting, Muppidi discussed additional efficacy findings from CHAMPION MG in a presentation titled, “Achievement of improved post-intervention status in patients with generalized myasthenia gravis treated with ravulizumab during the CHAMPION MG study.”
Specifically, the preplanned exploratory analysis concerned outcomes from MGFA-PIS, a standardized scale for assessing how a person’s clinical status changed in response to an intervention.
Patients could fall into any of four MGFA-PIS categories: worsened, unchanged, improved, or improved with minimal manifestation status (MMS), “which is defined as a [status of] minimal symptom burden, maybe minimal ocular [eye-related] symptoms, … that is not majorly disabling,” Muppidi said. Either of the latter two categories — improved, or improved with MMS — are considered a favorable response.
By the end of the main trial, 25.6% of Ultomiris-treated patients had achieved an improved with MMS status, and another 21.8% had improved but failed to reach MMS, meaning that about half achieved a favorable response.
The remaining patients in the Ultomiris group either saw no change (50%) or got worse (2.6%).
In contrast, those given placebo were less likely to see a favorable response, with 9.9% improving with MMS, 22.2% improving without reaching MMS, 60.5% experiencing no change, and 7.4% worsening.
After 60 weeks, 33.9% of those continuing treatment with Ultomiris in the OLE had achieved MMS, and 32.1% saw a clinical improvement without reaching MMS. That increase “suggests that longer-term treatment may be needed for some patients to achieve this status,” the researchers wrote.
Those who switched to Ultomiris from placebo in the OLE also saw increased rates of improvement with MMS (31.6%) and improvement alone (42.1%).
“Patients who were switched over from placebo to [Ultomiris] quickly caught up to the [Ultomiris] group, and a similar proportion of patients achieved improved and … minimal manifestations status,” Muppidi said.
Reductions in symptom severity
Patients who experienced MGFA-PIS improvements also experienced greater reductions in symptom severity, as assessed by the MG-ADL and Quantitative MG (QMG), a physician-reported measure of symptom severity.
They also were more likely to be considered a treatment responder on either scale, defined as having at least a three-point improvement in MG-ADL scores, or a five-point improvement in QMG scores.
The poster, “Ravulizumab for the Treatment of Generalized Myasthenia Gravis: Timing of Response,” further explored the timing of patients’ treatment responses in CHAMPION MG, as assessed by the MG-ADL and QMG.
Results indicated that 45.3% of Ultomiris-treated patients had achieved an MG-ADL response after two weeks, 75.5% after 26 weeks (about six months), and 82% after 60 weeks (a little more than a year).
The median time to first achieving an MG-ADL response was 29 days. Patients were more likely to have a later response to treatment — defined as a response more than four weeks after starting Ultomiris — if they were male, had a longer disease duration, or a history of MG crisis prior to study entry.
Findings for the QMG were similar, with response rates climbing continuously over time. The median time to a QMG response was about 18 weeks, or just more than four months.
“Further research is required to determine predictors of early, late, or no response to [Ultomiris],” the authors wrote.
A final poster, titled “Ravulizumab in Adults with Generalized Myasthenia Gravis: A Sub-Analysis of the Phase 3 CHAMPION MG Study According to Chronic IVIg Use at Study Entry,” explored patients’ response to treatment based on their prior use of IVIg, which was allowed to be used only during CHAMPION MG as a rescue therapy.
Of the 175 patients enrolled in CHAMPION MG, 96 previously had used IVIg, 46 of whom had received it chronically.
Results showed that MG-ADL and QMG responses after 26 (6 months) weeks were similar between patients who previously had received IVig and those who hadn’t in both the placebo and Ultomiris groups. Safety findings were similar.
Note: The Myasthenia Gravis News team is providing coverage of the American Academy of Neurology (AAN) 2023 Annual Meeting, held April 22-27. Go here to see the latest stories from the conference.