University of Louisville, Louisville, KY, USA.
John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ, USA.
Adv Ther. 2023 Nov;40(11):5115-5129. doi: 10.1007/s12325-023-02653-4. Epub 2023 Sep 14.
Pegcetacoplan is a targeted complement component 3 (C3) therapy approved for adults with paroxysmal nocturnal hemoglobinuria (PNH; US) or PNH plus anemia despite C5-targeted therapy for ≥ 3 months (EU). Patients with PNH receiving pegcetacoplan in the phase 3 PEGASUS trial who experienced injection site reactions (ISRs) mostly experienced mild events. We evaluated ISR incidence and severity with longer-term treatment in the PEGASUS cohort of the Study 307 open-label extension (307 OLE).
Patients from PEGASUS enrolled in the 307 OLE continued pegcetacoplan subcutaneous self-administration twice or three times weekly or every 3 days for an additional 48 weeks. ISRs were coded as adverse events (AEs) or treatment-emergent AEs (TEAEs) and summarized by MedDRA System Organ Class and Preferred Term.
As of August 27, 2021, 58/64 patients from PEGASUS completed an additional 48 weeks of treatment in the 307 OLE (median treatment duration 337.0 [range 55-344] days); 95.3% (61/64) of patients achieved compliance ≥ 80%. ISRs occurred in 9/64 (14.1%) patients in the 307 OLE, which was lower than observed at PEGASUS completion (20/77; 26.0%). Most patients with ISRs in the 307 OLE had events with a maximum severity of mild (7/9 patients; 77.8%). Injection site erythema and induration were the most common overall (4/64 patients each; 6.3%) and pegcetacoplan-related (3/64 patients each; 4.7%) ISRs. The exposure-adjusted rates of these events were each 6.5 per 100 patient-years. No ISRs were classified as severe or serious TEAEs or led to drug discontinuation.
Though ISRs were common, most were mild, and the percentage of patients reporting ISRs declined from PEGASUS through the 307 OLE. Patient compliance remained high, and no patients discontinued because of ISRs, suggesting that ISRs do not pose a barrier to long-term pegcetacoplan treatment.
ClinicalTrials.gov identifiers: NCT03500549 (PEGASUS) and NCT03531255 (307 OLE).
培塞卡泊是一种靶向补体成分 3（C3）的疗法，已获批准用于治疗阵发性夜间血红蛋白尿（PNH；美国）或 PNH 合并贫血，且患者接受 C5 靶向治疗至少 3 个月（欧盟）。接受培塞卡泊治疗的 PNH 患者在 3 期 PEGASUS 试验中发生注射部位反应（ISR），多数为轻度事件。我们在 Study 307 开放性扩展试验（307 OLE）的 PEGASUS 队列中评估了更长时间治疗的 ISR 发生率和严重程度。
PEGASUS 入组的患者在 307 OLE 中继续接受培塞卡泊皮下自我给药，每周 2 次或 3 次或每 3 天 1 次，额外治疗 48 周。ISR 编码为不良事件（AE）或治疗出现的不良事件（TEAE），并按 MedDRA 系统器官类别和首选术语进行总结。
截至 2021 年 8 月 27 日，58/64 名来自 PEGASUS 的患者在 307 OLE 中完成了另外 48 周的治疗（中位治疗持续时间 337.0[范围 55-344]天）；95.3%（61/64）的患者达到了≥80%的依从性。在 307 OLE 中，9/64（14.1%）的患者发生了 ISR，低于 PEGASUS 完成时（20/77；26.0%）。307 OLE 中大多数 ISR 患者的最大严重程度为轻度（7/9 例；77.8%）。注射部位红斑和硬结是最常见的总体（64 例患者各有 4 例；6.3%）和培塞卡泊相关（64 例患者各有 3 例；4.7%）ISR。这些事件的暴露调整发生率均为每 100 患者-年 6.5 例。没有 ISR 被归类为严重或严重的 TEAEs，也没有导致药物停药。
虽然 ISR 很常见，但大多数为轻度，且报告 ISR 的患者比例从 PEGASUS 降至 307 OLE。患者的依从性仍然很高，没有患者因 ISR 而停药，这表明 ISR 不会成为长期培塞卡泊治疗的障碍。
ClinicalTrials.gov 标识符：NCT03500549（PEGASUS）和 NCT03531255（307 OLE）。
