Medication Compliance High With Self-Administered Ziluocoplan in Myasthenia Gravis

James F. Howard, MD

A recently presented post-hoc analysis of the long-term, RAISE-XT study (NCT04225871) highlighted the high compliance rates of zilucoplan (Zilbrysq; UCB Pharma), a recently approved complement C5 inhibitor for generalized myasthenia gravis (gMG).¹

In the extension, patients received once-daily subcutaneous zilucoplan 0.3 mg/kg by self-injection. Presented at the 2024 American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) Annual Meeting, held October 15-18, in Savannah, Georgia, 95% (189 of 199) of patients with available data reported taking at least 95% of their medication over a median of 2.2 (0.1-5.6) years. These results remained high despite 97.0% (194 of 200) of enrolled patients experiencing a treatment-emergent adverse event (TEAE).

Led by James F. Howard, MD, Distinguished Professor of Neuromuscular Disease and professor of neurology at The University of North Carolina at Chapel Hill School of Medicine, patients reported taking a mean percentage of 99.2% of their medication. Data for the subgroups of age, sex, disease duration, and baseline Myasthenia Gravis-Activities of Daily Living (MG-ADL) scores were consistent with those of the overall population, as the mean percentage of medication taken for all subgroups was at least 98.4% of doses.

Zilucoplan gained FDA approval in October 2023 based on data from the placebo-controlled, phase 3 RAISE study (NCT04115293), the double-blind trial that preceded RAISE-XT. In the study, zilucoplan met its primary end point, demonstrating a placebo-corrected mean improvement of 2.09 points on MG-ADL over a 12-week treatment period. On secondary outcomes, investigators reported a clinically meaningful reduction in Quantitative Myasthenia Gravis score after 12 weeks with zilucoplan (least squares [LS] mean change, –6.19; 95% CI, –7.29 to –5.08) vs placebo (LS mean change, –3.25; 95% CI, –4.32 to –2.17; LS mean difference, –2.94; 95% CI, –4.39 to –1.49; P <.0001).²

READ MORE: NeuroVoices: Richard Nowak, MD, MS, on the MINT Trial of Inebilizumab in Myasthenia Gravis

At AANEM 2024, an additional interim analysis of RAISE-XT highlighted the long-term efficacy and safety profile of zilucoplan in treating gMG over a 120-week period. 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. In the analysis, researchers reported a mean reduction of 7.14 (SE, 0.44) on MG-ADL from the double-blind baseline to week 120 in the pooled zilucoplan 0.3 mg/kg group.³

In terms of safety, the interim analysis revealed that COVID-19 and myasthenia gravis worsening were the most common TEAEs, occurring in 71 (35.5%) and 59 (29.5%) of patients, respectively. In addition, 81 (40.5%) of participants reported a serious TEAE.

A previous interim analysis of RAISE-XT revealed 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. 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 60.⁴

These data, presented at the 2023 AANEM meeting, also 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. Additionally, the investigators observed no significant differences in the baseline characteristics of week 1 responders compared to the overall gMG sample population.

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REFERENCES
1. Ruzhansky K, Freimer M, Leite MS, et al. Compliance to daily self-administered subcutaneous zilucoplan in patients with generalized myasthenia gravis: a post hoc analysis of the RAISE-XT study. Presented at: 2024 AANEM Annual Meeting; October 15-18; Savannah, GA. ABSTRACT 264
2. Howard JF, Bresch S, Genge A, et al. Safety and efficacy of zilucoplan in patients with generalized myasthia gravis (RAISE): a randomized, double-blind, placebo-controlled, phase 3 study. 2023;22(5):395-406. doi:10.1016/S1474-4422(23)00080-7
3. 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.
4. 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.