Sharma Shashikant, Gupta Vishali, Maiti Aniruddha, Natesh Sribhargava, Saxena Sandeep, Dave Vivek, Parmar Vimal, Sampangi Raju, Murthy Hemanth, Dharwadkar Sandhya, Yadav Naresh Kumar, Joshi Shrinivas, Mayor Rahul, Ratra Dhanashree, Basu Soumyava, Goel Neha, Chaturvedi Alok, Patel Ronak, Jose Vinu
Medical Affairs, Intas Pharmaceuticals Ltd, Ahmedabad, Gujarat, India.
Advanced Eye Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Int J Retina Vitreous. 2021 Mar 24;7(1):24. doi: 10.1186/s40942-021-00293-w.
Razumab™ (world's first biosimilar ranibizumab) is approved for several macular disorders including wet age-related macular degeneration (AMD). We evaluated the safety and efficacy of biosimilar ranibizumab in wet AMD.
This prospective, multicentre, rAnibizumab bioSimilar Safety Efficacy postmarkeTing (ASSET) study enrolled patients aged ≥ 50 years with wet AMD having best-corrected visual acuity (BCVA) between 20/40 and 20/320. The patients received intravitreal biosimilar ranibizumab 0.5 mg every 4 weeks for 24 weeks. Safety endpoints included the incidence of adverse events (AEs), serious AEs (SAEs), and immunoreactivity after 6 months. The efficacy endpoints were the proportion of patients who lose fewer than 15 letters, increase in BCVA, change in central retinal thickness (CRT), and change in Visual Function Questionnaire-25 (VFQ-25) score, from baseline to 24 weeks.
Of the 126 enrolled patients, majority (95.24%) of the patients received all 6 doses of biosimilar ranibizumab (total 3 mg). Nineteen AEs were reported (n = 16; 12.7%); majority (78.9%) were mild. There were no serious AEs reported, except one AE of death which was unrelated to the study drug. None of the patients discontinued the study due to an AE. The most common ocular AE was increase in intraocular pressure (4 events) and non-ocular AE was pyrexia (5 events). A total of 7.9% (10/126) patients prior to dosing and 7.1% (9/126) patients post-treatment were positive for anti-ranibizumab antibodies. No AEs suggestive of immunogenicity were noted. At 24-weeks, 97.60% patients in the intent-to-treat (ITT) population (N = 125) and 97.41% patients in the per-protocol (PP) population (N = 116) lost < 15 letters from baseline visual acuity. In the ITT and PP populations, 31.20% and 32.76% patients, respectively, showed improved visual acuity by ≥ 15 letters. Significant improvements in BCVA (mean difference: 8.8, 9.2, p < 0.001 for ITT, PP) and VFQ-25 (8.5, 9.2, p < 0.001 for ITT, PP) were seen; CRT reduced significantly (125 µm, 119.3 µm, p < 0.001 for ITT, PP).
Razumab™ (world's first biosimilar ranibizumab) was well-tolerated without new safety concerns and significantly improved visual acuity in wet AMD patients. Trial registration CTRI/2016/03/006739. Registered 18 March 2016-Prospectively registered, http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=13141&EncHid=&userName=2016/03/006739.
Razumab™（全球首个雷珠单抗生物类似药）已被批准用于多种黄斑疾病，包括湿性年龄相关性黄斑变性（AMD）。我们评估了雷珠单抗生物类似药在湿性AMD中的安全性和有效性。
这项前瞻性、多中心、雷珠单抗生物类似药上市后安全性和有效性（ASSET）研究纳入了年龄≥50岁、最佳矫正视力（BCVA）在20/40至20/320之间的湿性AMD患者。患者每4周接受一次玻璃体内注射0.5mg雷珠单抗生物类似药，共治疗24周。安全性终点包括不良事件（AE）、严重不良事件（SAE）的发生率以及6个月后的免疫反应性。有效性终点是从基线到24周时视力下降少于15个字母的患者比例、BCVA的增加、中心视网膜厚度（CRT）的变化以及视觉功能问卷-25（VFQ-25）评分的变化。
在126名入组患者中，大多数（95.24%）患者接受了全部6剂雷珠单抗生物类似药（总计3mg）。报告了19例AE（n = 16；12.7%）；大多数（78.9%）为轻度。除1例与研究药物无关的死亡AE外，未报告严重AE。没有患者因AE而停止研究。最常见的眼部AE是眼压升高（4例），非眼部AE是发热（5例）。共有7.9%（10/126）的患者在给药前和7.1%（9/126）的患者在治疗后抗雷珠单抗抗体呈阳性。未观察到提示免疫原性的AE。在24周时，意向性治疗（ITT）人群（N = 125）中的97.60%患者和符合方案（PP）人群（N = 116）中的97.41%患者与基线视力相比视力下降少于15个字母。在ITT和PP人群中，分别有31.20%和32.76%的患者视力提高≥15个字母。BCVA（ITT组平均差异：8.8，PP组9.2，p < 0.001）和VFQ-25（ITT组8.5，PP组9.2，p < 0.001）有显著改善；CRT显著降低（ITT组125μm，PP组119.3μm，p < 0.001）。
Razumab™（全球首个雷珠单抗生物类似药）耐受性良好，没有新的安全问题，并且显著改善了湿性AMD患者的视力。试验注册号CTRI/2016/03/006739。于2016年3月18日注册——前瞻性注册，http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=13141&EncHid=&userName=2016/03/006739。
