Bischoff Herve, O'Connor Neil K, Kim Jamie, Popescu Bogdan V, Bigot Cecile, Pradhan Sumita, Chakraborty Rusha, Jaison Litha, Majeed Fathima, Park Lisa S, Boudali Lotfi, Detappe Alexandre, Pivot Xavier, Coliat Pierre
Institut de Cancérologie de Strasbourg - Paul Strauss Cancer Center, 17 rue Albert Calmette, 67033, Strasbourg, France.
Prestige BioPharma Ltd, 21 Biopolis Road, #04-24 Nucleos South Building, Singapore, Singapore.
Drugs R D. 2025 Mar;25(1):67-77. doi: 10.1007/s40268-025-00505-w. Epub 2025 Apr 2.
The high cost of trastuzumab (Herceptin) limits its accessibility for patients worldwide. Biosimilars, such as Tuznue (HD201), represent a promising alternative to improve access to this essential therapy for HER2-positive breast cancer. This study aims to assess the similarity of Tuznue with the reference product Herceptin through comprehensive analytical and biofunctional evaluations, ensuring similar quality, safety, and efficacy profiles.
Multiple analytical methods were performed to assess key quality attributes of Tuznue and Herceptin. Physicochemical properties, HER2 binding, anti-proliferative activity, antibody-dependent cellular cytotoxicity, complement dependent cytotoxicity, and Fc receptor binding were evaluated through various bioassays. Statistical analyses were conducted according to a risk-based tiered approach (Tiers 1-3) to demonstrate biosimilarity. The equivalence margin for critical quality attributes (Tier 1) was set at ±1.5 standard deviations from the reference product's mean.
Tuznue showed highly comparable results to Herceptin across all evaluated biofunctional assays. HER2 binding affinity, inhibition of cellular proliferation, and antibody-dependent cellular cytotoxicity activity were equivalent between Tuznue and Herceptin, with 90% confidence intervals within predefined equivalence margins. No complement dependent cytotoxicity activity was observed for either product. Differences in glycosylation profiles were identified but did not affect critical biofunctional properties. Fc receptor binding remained consistent across all tested lots.
The comprehensive analytical characterization confirms the biosimilarity of Tuznue to Herceptin. This supports Tuznue as a safe and effective alternative, offering a more affordable option for patients and healthcare systems. Biosimilar development requires overcoming inherent challenges, particularly when reference products exhibit variability in quality attributes over time. Regulatory guidance and scientific rigor are essential to ensuring biosimilar similarity, facilitating broader patient access to life-saving therapies.
曲妥珠单抗（赫赛汀）的高昂成本限制了全球患者对其的可及性。生物类似药，如Tuznue（HD201），是一种有前景的替代药物，有望改善HER2阳性乳腺癌患者获得这种关键治疗的机会。本研究旨在通过全面的分析和生物功能评估，评估Tuznue与参比产品赫赛汀的相似性，确保其质量、安全性和疗效特征相似。
采用多种分析方法评估Tuznue和赫赛汀的关键质量属性。通过各种生物测定评估其物理化学性质、HER2结合、抗增殖活性、抗体依赖性细胞毒性、补体依赖性细胞毒性和Fc受体结合。根据基于风险的分层方法（第1 - 3层）进行统计分析以证明生物相似性。关键质量属性（第1层）的等效性界限设定为偏离参比产品均值±1.5个标准差。
在所有评估的生物功能测定中，Tuznue与赫赛汀的结果高度可比。Tuznue和赫赛汀之间的HER2结合亲和力、细胞增殖抑制和抗体依赖性细胞毒性活性相当，90%置信区间在预定义的等效性界限内。两种产品均未观察到补体依赖性细胞毒性活性。鉴定出糖基化谱存在差异，但不影响关键生物功能特性。所有测试批次的Fc受体结合保持一致。
全面的分析表征证实了Tuznue与赫赛汀的生物相似性。这支持Tuznue作为一种安全有效的替代药物，为患者和医疗系统提供了更经济实惠的选择。生物类似药的研发需要克服内在挑战，特别是当参比产品的质量属性随时间表现出变异性时。监管指导和科学严谨性对于确保生物类似药的相似性至关重要，有助于更广泛的患者获得挽救生命的治疗。
