Freimer Miriam, Desai Urvi, Govindarajan Raghav, Kang Min K, Khan Shaida, Khatri Bhupendra, Levine Todd, Macwan Samir, Shieh Perry B, Weiss Michael D, Bloemers Jos, Boroojerdi Babak, Delicha Eumorphia Maria, Lavrov Andreea, Singh Puneet, Howard James F
Department of Neurology, The Ohio State University Wexner Medical Center, 395 West 12th Avenue, 7th Floor, Columbus, OH 43210, USA.
Atrium Health, Wake Forest University, Charlotte, NC, USA.
Ther Adv Neurol Disord. 2025 Jul 5;18:17562864251347283. doi: 10.1177/17562864251347283. eCollection 2025.
Zilucoplan, a peptide complement component 5 (C5) inhibitor, is self-administered as a subcutaneous (SC) injection, which offers an alternative to intravenous infusion of antibody-based complement C5 inhibitors.
To evaluate subcutaneous zilucoplan in adults with acetylcholine receptor autoantibody-positive generalised myasthenia gravis (gMG) who switched from intravenous complement C5 inhibitors to zilucoplan.
MG0017 (NCT05514873) was a phase IIIb, open-label, single-arm study.
Eligible patients had clinically stable gMG on an intravenous complement C5 inhibitor and were willing to switch to zilucoplan. Patients received a 12-week treatment period of daily subcutaneous zilucoplan 0.3 mg/kg. Incidence of treatment-emergent adverse events (TEAEs) was the primary endpoint. Change from baseline in the Myasthenia Gravis Activities of Daily Living (MG-ADL) score at Week 12 was a secondary endpoint. Treatment preference (Week 12) and treatment satisfaction (9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9)) were both exploratory endpoints. Assessments by prior intravenous complement C5 inhibitor were conducted post hoc.
Twenty-six patients enrolled and received zilucoplan; 16 switched from eculizumab and 10 from ravulizumab. TEAEs occurred in 19/26 (73.1%) patients and were mostly mild in severity. At Week 12, least squares (LS) mean (95% confidence interval) MG-ADL scores improved from baseline by -1.15 (-2.11, -0.19), = 0.0217 and Quantitative MG (QMG) scores by -1.24 (-2.64, 0.16), = 0.0802. Clinically meaningful improvement from baseline in mean MG-ADL and QMG scores was observed at Week 12 among patients who switched from ravulizumab (-2.41 (-4.52, -0.30; = 0.0307) and -3.52 (-6.14, -0.90; = 0.0149), respectively). At Week 12, 76.9% ( = 20) patients preferred subcutaneous injection compared with intravenous infusion. Mean (standard deviation) changes from baseline in the TSQM-9 Global Satisfaction, Effectiveness and Convenience subscores at Week 12 were +19.410 (27.429), +13.889 (21.534) and +21.739 (19.955), respectively. Complement inhibition increased from baseline and was complete (>95%) by Week 2 and maintained to Week 12.
Zilucoplan demonstrated a favourable safety profile. gMG symptoms improved during zilucoplan treatment; this was clinically meaningful for those switching from ravulizumab.
ClinicalTrials.gov (NCT05514873); 22 August 2022. https://clinicaltrials.gov/study/NCT05514873.
zilucoplan是一种肽类补体成分5（C5）抑制剂，通过皮下注射自我给药，为基于抗体的补体C5抑制剂静脉输注提供了一种替代方法。
评估皮下注射zilucoplan对从静脉注射补体C5抑制剂转换为zilucoplan的乙酰胆碱受体自身抗体阳性全身型重症肌无力（gMG）成人患者的疗效。
MG0017（NCT05514873）是一项IIIb期、开放标签、单臂研究。
符合条件的患者在静脉注射补体C5抑制剂治疗下临床症状稳定，且愿意转换为zilucoplan治疗。患者接受为期12周的每日皮下注射zilucoplan 0.3mg/kg治疗。治疗期间出现的不良事件（TEAE）发生率是主要终点。第12周时重症肌无力日常生活活动（MG-ADL）评分相对于基线的变化是次要终点。治疗偏好（第12周）和治疗满意度（9项药物治疗满意度问卷（TSQM-9））均为探索性终点。对先前静脉注射补体C5抑制剂的评估在事后进行。
26名患者入组并接受了zilucoplan治疗；16名从依库珠单抗转换而来，10名从ravulizumab转换而来。19/26（73.1%）的患者发生了TEAE，严重程度大多为轻度。在第12周时，最小二乘（LS）均值（95%置信区间）的MG-ADL评分相对于基线改善了-1.15（-2.11，-0.19），P = 0.0217，定量重症肌无力（QMG）评分改善了-1.24（-2.64，0.16），P = 0.0802。在从ravulizumab转换而来的患者中，第12周时观察到MG-ADL和QMG评分相对于基线有临床意义的改善（分别为-2.41（-4.52，-0.30）；P = 0.0307和-3.52（-6.14，-0.90）；P = 0.0149）。在第12周时，76.9%（n = 20）的患者更喜欢皮下注射而非静脉输注。第12周时，TSQM-9总体满意度、有效性和便利性子评分相对于基线的平均（标准差）变化分别为+19.410（27.429）、+13.889（21.534）和+21.739（19.955）。补体抑制作用从基线水平增加，在第2周时达到完全抑制（>95%）并维持至第12周。
zilucoplan显示出良好的安全性。在zilucoplan治疗期间gMG症状有所改善；这对从ravulizumab转换而来的患者具有临床意义。
ClinicalTrials.gov（NCT05514873）；2022年8月22日。https://clinicaltrials.gov/study/NCT0551
