Deodhar Sarika, Loganathan Subramanian, Kadadanamari Subbarama Reddy Ramesh, Ranganna Gopinath M, Liu Shiyao, Hummel Matthew A, Daniluk Stefan, Hanczewska Anna, Vekovska Kamelia, Zegadlo-Mylik Maria, Pulka Grazyna, -Holz Elena Wolff
Clinical Development and Medical Affairs, Biocon Biologics Ltd., Biocon House, Tower 3, Semicon Park, Plot No 29-P1 & 31-P, KIADB Industrial Area, Electronic City Phase-2, Bangalore, Karnataka, 560100, India.
Mylan Pharmaceuticals Pvt Ltd (A Viatris Company), Bengaluru, Karnataka, India.
Adv Ther. 2025 Jun 10. doi: 10.1007/s12325-025-03240-5.
This study was conducted to fulfill the FDA requirement for the designation of adalimumab-fkjp, an FDA-approved biosimilar, as an 'interchangeable' biosimilar to the reference adalimumab. The primary objective was to evaluate the interchangeability of adalimumab-fkjp (low concentration, 40 mg/0.8 mL) with reference adalimumab (high concentration, 40 mg/0.4 mL) by comparing adalimumab steady-state pharmacokinetics (PK) between switching and non-switching arms. The efficacy, safety, and immunogenicity were also evaluated.
In this randomized, double-blind, parallel-group study in patients with moderate-to-severe chronic plaque psoriasis (PPs) a total of 386 patients (134 F/252 M) with PPs for ≥ 6 months involving body surface area ≥ 10% and having a Psoriasis Area and Severity Index (PASI) ≥ 12 and static Physicians Global Assessment (sPGA) ≥ 3 (moderate) were enrolled into the run-in period to receive reference adalimumab (80 mg, Week 1; 40 mg biweekly, Weeks 2-10). At Week 12, patients with PASI ≥ 50 (n = 374) were randomized 1:1 to continue receiving reference adalimumab (n = 193; 40 mg/0.4 mL biweekly, Weeks 12-26) or undergo repeated switches between 40 mg/0.8 mL adalimumab-fkjp and 40 mg/0.4 mL reference adalimumab (n = 181; reference adalimumab-fkjp, Weeks 12 and 14; adalimumab, Weeks 16 and 18; and adalimumab-fkjp, Weeks 20, 22, 24, and 26). The assessments included PK (primary endpoints: AUC and C; secondary endpoints: T, C, and C), efficacy (proportion of PASI-50, PASI-75, PASI-90, and PASI-100 responders and sPGA success of clear or almost clear at Week 28), safety, and immunogenicity.
The mean steady-state serum PK profiles were similar in both switching and non-switching arms. The 90% confidence intervals of LS mean ratios for AUC [104.76 (98.23-111.74%)], C [104.23 (95.85-113.36%)], and C [107.85 (99.99-116.37%)] were within the bioequivalent range of 80.00-125.00%. The overall number and proportion of patients with PASI responses and sPGA success were highly similar between the two arms at Week 28. Safety and immunogenicity profiles were comparable between treatment arms.
Patients receiving adalimumab-fkjp (low concentration) and reference adalimumab (high concentration) in alternate fashion had similar PK, efficacy, safety, and immunogenicity profile. Interchangeability status has been granted to adalimumab-fkjp.
Clinicaltrial.gov identifier: NCT05637515, EudraCT No:2021-006015-29.
本研究旨在满足美国食品药品监督管理局（FDA）对阿达木单抗 - fkjp（一种FDA批准的生物类似药）指定为参考阿达木单抗的“可互换”生物类似药的要求。主要目的是通过比较换药组和未换药组之间阿达木单抗的稳态药代动力学（PK），评估阿达木单抗 - fkjp（低浓度，40mg/0.8mL）与参考阿达木单抗（高浓度，40mg/0.4mL）的可互换性。还评估了疗效、安全性和免疫原性。
在这项针对中度至重度慢性斑块状银屑病（PPs）患者的随机、双盲、平行组研究中，共有386例患者（134例女性/252例男性）入组，这些患者患有PPs≥6个月，累及体表面积≥10%，银屑病面积和严重程度指数（PASI）≥12且静态医师整体评估（sPGA）≥3（中度），进入导入期接受参考阿达木单抗（第1周80mg；第2 - 10周每两周40mg）。在第12周时，PASI≥50的患者（n = 374）按1:1随机分组，继续接受参考阿达木单抗（n = 193；第12 - 26周每两周40mg/0.4mL）或在40mg/0.8mL阿达木单抗 - fkjp和40mg/0.4mL参考阿达木单抗之间反复换药（n = 181；第12周和第14周为阿达木单抗 - fkjp，第16周和第18周为阿达木单抗，第20、22、24和26周为阿达木单抗 - fkjp）。评估包括PK（主要终点：AUC和C；次要终点：T、C和C）、疗效（第28周时达到PASI - 50、PASI - 75、PASI - 90和PASI - 100缓解的患者比例以及sPGA达到清除或几乎清除的成功率）、安全性和免疫原性。
换药组和未换药组的平均稳态血清PK曲线相似。AUC [104.76（98.23 - 111.74%）]、C [104.23（95.85 - 113.36%）]和C [107.85（99.99 - 116.37%）]的LS均值比的90%置信区间在生物等效范围80.00 - 125.00%内。在第28周时，两组中达到PASI缓解和sPGA成功的患者总数和比例高度相似。治疗组之间的安全性和免疫原性概况具有可比性。
交替接受阿达木单抗 - fkjp（低浓度）和参考阿达木单抗（高浓度）的患者具有相似的PK、疗效、安全性和免疫原性概况。阿达木单抗 - fkjp已被授予可互换状态。
Clinicaltrial.gov标识符：NCT05637515，欧盟临床试验编号：2021 - 006015 - 29。
