RAISE-XT Interim Analysis Shows Sustained Efficacy of Long-Term Zilucoplan Treatment in Generalized Myasthenia Gravis

Maria Isabel Leite, MD, DPhil

(Credit: European School of Neuroimmunology)

In a new interim analysis of the phase 3 RAISE-XT (NCT04225871), zilucoplan (Zilbrysq; UCB Pharma), an FDA-approved macrocyclic peptide complement component 5 inhibitor, demonstrated sustained efficacy and a favorable safety profile in patients with acetylcholine receptor autoantibody-positive generalized myasthenia gravis (gMG) up to 120 weeks on treatment.¹

As of the data cutoff date, November 11, 2023, the median exposure to zilucoplan was 2.2 (range, 0.11–5.6) years among 200 patients enrolled in RAISE-XT. Of the 183 patients treated with zilucoplan 0.3mg/kg or placebo in the qualifying study, 93 of the participants continued zilucoplan 0.3mg/kg and 90 switched from placebo to zilucoplan 0.3mg/kg. Researchers reported a mean reduction of 7.14 (standard error, 0.44) on Myasthenia Gravis Activities of Daily Living (MG-ADL) from the double-blind baseline to week 120 the in pooled zilucoplan 0.3mg/kg group.

RAISE-XT, an ongoing, phase 3, open-label extension study, enrolled adults with gMG who completed a qualifying double-blind study (NCT03315130/NCT04115293). In the study, investigators had patients self-administer daily subcutaneous injections of zilucoplan 0.3mg/kg, with the primary outcome focused on safety, namely the incidence of treatment-emergent adverse events (TEAEs). Researchers analyzed the change from double-blind baseline to week 120 in MG-ADL score for pooled data from those who received zilucoplan 0.3mg/kg or placebo in the qualifying studies.

Presented at the 2024 American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) meeting, held October 15-18, in Savannah, Georgia, by senior author Maria Isabel Leite, MD, DPhil, associate professor and consultant neurologist at University of Oxford Hospitals, and colleagues, TEAEs occurred in 194 (97.0%) patients. In addition, 81 (40.5%) of participants reported a serious TEAE. Investigators observed that COVID-19 and myasthenia gravis worsening were the most common TEAEs, occurring in 71 (35.5%) and 59 (29.5%) patients, respectively.

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A prior interim analysis of the phase 3 RAISE-XT showed that patients with gMG who responded to zilucoplan at week 1 maintained their response for almost 90% of their time on long-term treatment regardless of their baseline characteristics. Presented at the 2023 AANEM meeting by lead author Miriam Freimer, MD, clinical professor of neurology at The Ohio State University Wexner Medical Center, and colleagues, these previous findings support the early use of zilucoplan and the long-term benefit of the treatment in a broad patient population for those living with gMG.²

Among the participants randomized to receive zilucoplan treatment in RAISE-XT (n = 93), 43.0% (n = 40) were considered responders on MG-ADL and 33.3% of patients (n = 3) were responders Quantitative Myasthenia Gravis (QMG) at week 1. In this set of patients, more than 80% and more than 85%, respectively, remained as responders at each assessment through week 60. For this analysis, investigators defined MG-ADL and QMG responders by at least a 3-point and at least a 5-point reduction, respectively, from the double-blind baseline without the patients needing rescue therapy.

Results showed that responders at week 1 maintained their response for 88.1% and 88.8% of their total time on zilucoplan treatment, respectively, with a median treatment duration of 450 days. In addition, the investigators noted no relevant differences in the baseline characteristics of responders at week 1 compared with the overall gMG sample population.

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REFERENCES
1. Howard JF, Freimer M, Genge A, et al. Long-Term Safety and Efficacy of Zilucoplan in Generalized Myasthenia Gravis: 120-Week Interim Analysis of RAISE-XT. Presented at: 2024 AANEM; October 15-18; Savannah, Georgia.
2. Freimer M, Leite MI, Vu T, et al. Early Responders with Zilucoplan: An Interim Analysis of RAISE-XT in Patients with Generalized Myasthenia Gravis. Presented at: American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) meeting; November 1-4, 2023; Phoenix, AZ. Abstract 41.