MDA 2025: Responses to Zilbrysq now at over 2 years in RAISE-XT
Most adults with gMG note easing of disease severity in extension study
More than two years of treatment with Zilbrysq (zilucoplan) continues to be associated with sustained clinical responses in adults with generalized myasthenia gravis (gMG), according to interim analyses of the long-term Phase 3 RAISE-XT extension study.
These new findings, consistent with earlier interim trial analyses, were presented in a pair of posters at the Muscular Dystrophy Association’s (MDA) Clinical & Scientific Conference running March 16-19 in Texas and virtually. The studies were funded by UCB, the company that markets Zilbrysq.
Self-administered as a once daily under-the-skin injection, Zilbrysq is approved in the U.S. for adults with gMG who are positive for antibodies targeting the acetylcholine receptor (AChR), the most common type of MG-causing antibody, with similar approvals elsewhere.
It works to block the activation of the complement cascade, a part of the immune system thought to be implicated in the autoimmune attacks that hamper nerve-muscle communication in gMG.
200 adults with gMG enrolled in the open-label RAISE-XT trial
In the Phase 3 RAISE clinical trial (NCT04115293), 174 adults with AChR-positive gMG were randomly assigned to daily injections of Zilbrysq (0.3 mg/g) or a placebo for about three months (12 weeks).
Results showed that a higher proportion of Zilbrysq-treated patients achieved clinically meaningful reductions in disease severity compared with the placebo group, as assessed using the MG Activities of Daily Living (MG-ADL; a patient-reported measure) and the Quantitative MG (QMG; a clinician-evaluated measure) scales.
RAISE-XT (NCT04225871) then enrolled 200 adults who had completed RAISE or an earlier 12-week Phase 2 clinical trial (NCT03315130), all of whom are receiving long-term, daily treatment with Zilbrysq. This global extension study is due to conclude in June 2026.
At last year’s MDA conference, researchers presented data covering 48 weeks (nearly a year) in RAISE-XT, amounting to 60 weeks, or more than a year, of total Zilbrysq treatment for those assigned to the therapy in the initial trials.
Sustained reductions in disease severity at 48 weeks were seen for those initially on Zilbrysq, and rapid and sustained improvements were reported in adults who switched to treatment from a placebo.
The proportion of patients considered to be MG-ADL responders (showing at least a three-point improvement) and QMG responders (at least a five-point improvement) increased between week 12 — the end of the main trial and the beginning of RAISE-XT — and week 60 for both groups.
Likewise, the proportion who achieved minimal symptom expression (MSE) — defined as an MG-ADL score of zero or one — rose between weeks 12 and 60 in each group.
About 50% of main trial’s nonresponders became responders 2 weeks later
In the poster “Response over time with zilucoplan in generalized myasthenia gravis: Post hoc analysis of RAISE-XT 60-week follow up,” researchers further explored week 60 responder data.
Of the 74.2% of Zilbrysq-treated patients who were considered to be MG-ADL responders when the main trials ended (week 12), 89.1% continued to be so through week 60. Likewise, of the 59.8% of Zilbrysq-treated patients who were QMG responders at week 12, 94.3% were still responders at week 60.
For those considered nonresponders at week 12, about half became responders by week 14 — two weeks into RAISE-XT — under scores for both the MG-ADL and QMG, with similar rates sustained up to week 60.
“These data demonstrate the benefit of long-term [Zilbrysq] treatment,” the researchers wrote.
In the poster “Response rates with zilucoplan in generalized myasthenia gravis: 120-week interim analysis of RAISE-XT,” researchers reported on patient responses with up to 120 weeks, or more than two years, of treatment.
For this analysis, starting at week 24 — 12 weeks into RAISE-XT — scientists pooled data from patients randomized to Zilbrysq and those who moved from a placebo to treatment in the extension study.
Most treatment-emergent side effects reported to be mild or moderate
At the November 2023 data cutoff date, 73% of the initial 200 people enrolled were still taking part in RAISE-XT, with no discontinuations related to a lack of treatment efficacy. Median treatment duration with Zilbrysq was 2.2 years.
At week 24, 83.2% of patients in the pooled group were considered MG-ADL responders, which was sustained up to week 120 (87.7%). Likewise, 76.2% were QMG responders at week 24, with a response rate of 85.7% at week 120. The MSE response rate rose from 31.7% at week 24 to 41.4% at week 120.
Researchers also noted similar improvements in other measures of symptom severity, life quality, and fatigue.
Overall, “high … responder rates were sustained through week 120 of [Zilbrysq] treatment in patients with gMG,” they wrote.
Zilbrysq was found to be well tolerated with long-term use, with the majority of reported treatment-emergent side effects being mild or moderate in severity. The most common were COVID-19 (35.5%), gMG worsening (29.5%), and headache (22%).
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