强生IL-23受体拮抗新药JNJ-77242113：银屑病疗效显著，3期临床加速推进

药融云数据监测显示：JNJ-77242113（其他研发代码：JNJ-2113,原名PN-235）为一款正在开发中的口服IL-23受体拮抗肽类候选新药，本品最早由Protagonist Therapeutics Inc公司开发，后被强生/J&J收购执行权益合作。

双方最早合作始于2017年。2021年7月，强生与Protagonist合作开发了3种口服IL-23受体拮抗肽类候选新药，后确定其中之一即JNJ-77242113，目前最快适应症在3期临床试验阶段。

截图来源：药融云数据库

JNJ-77242113的2期临床试验（代号：FRONTIER 1；ClinicalTrials.gov 登记号NCT05223868）结果于2024年2月8日发布在《NEJM/新英格兰医学杂志》上。

本项FRONTIER 1研究是一项剂量探索、随机、安慰剂对照临床试验，旨在评估JNJ-77242113疗效和安全性。研究中设置了不同剂量组（从25 mg至100 mg，每日一次或两次给药模式）和一个安慰剂组，全面评估该药物的剂量-效应关系。主要临床终点是第16周时实现PASI 75反应（即PASI评分与基线相比降低至少75%）。

本次研究共有255例患者入组，其中78%曾接受过系统治疗；银屑病患者平均持续时间18.2年。最大JNJ-77242113用药剂量组（每日两次100 mg）实现了79%的PASI 75反应率，最小NJ-77242113用药剂量组（每日一次25 mg）实现37%的PASI 75反应率，均较安慰剂组9%的反应率提高显著。

本次临床试验结果表明，JNJ-77242113在缓解斑块型银屑病症状方面具有潜在的临床效果。

An Oral Interleukin-23–Receptor Antagonist Peptide for Plaque Psoriasis. N Engl J Med 2024

JNJ-77242113治疗组的PASI指数改善百分比明显高于安慰剂组，且达到PASI绝对阈值和BSA绝对阈值(治疗目标)的患者比例也明显增加并表现出剂量依赖性。

不同剂量的JNJ-77242113治疗组与安慰剂组达到PASI绝对阈值、BSA绝对阈值比例

截止2024年3月27日，Protagonist Therapeutics公司(NASDAQ:PTGX)市值约16.6亿美元；每股价格为28.48美元。公司上市日期为2016年08月11日。最早成立于2006年。截止2024年8月20日，市值为24.45亿美元。

Protagonist Therapeutics产品布局

JNJ-77242113正在进行2项3期临床试验，与BMS deucravacitinib氘代新药TYK2头对头比较。

附：上述NEJM原文：An Oral Interleukin-23-Receptor Antagonist Peptide for Plaque Psoriasis

Abstract
        Background：The use of monoclonal antibodies has changed the treatment of several immune-mediated inflammatory diseases, including psoriasis. However, these large proteins must be administered by injection. JNJ-77242113 is a novel, orally administered interleukin-23-receptor antagonist peptide that selectively blocks interleukin-23 signaling and downstream cytokine production.
        Methods：In this phase 2 dose-finding trial, we randomly assigned patients with moderate-to-severe plaque psoriasis to receive JNJ-77242113 at a dose of 25 mg once daily, 25 mg twice daily, 50 mg once daily, 100 mg once daily, or 100 mg twice daily or placebo for 16 weeks. The primary end point was a reduction from baseline of at least 75% in the Psoriasis Area and Severity Index (PASI) score (PASI 75 response; PASI scores range from 0 to 72, with higher scores indicating greater extent or severity of psoriasis) at week 16.
        Results：A total of 255 patients underwent randomization. The mean PASI score at baseline was 19.1. The mean duration of psoriasis was 18.2 years, and 78% of the patients across all the trial groups had previously received systemic treatments. At week 16, the percentages of patients with a PASI 75 response were higher among those in the JNJ-77242113 groups (37%, 51%, 58%, 65%, and 79% in the 25-mg once-daily, 25-mg twice-daily, 50-mg once-daily, 100-mg once-daily, and 100-mg twice-daily groups, respectively) than among those in the placebo group (9%), a finding that showed a significant dose-response relationship (P<0.001). The most common adverse events included coronavirus disease 2019 (in 12% of the patients in the placebo group and in 11% of those across the JNJ-77242113 dose groups) and nasopharyngitis (in 5% and 7%, respectively). The percentages of patients who had at least one adverse event were similar in the combined JNJ-77242113 dose group (52%) and the placebo group (51%). There was no evidence of a dose-related increase in adverse events across the JNJ-77242113 dose groups.
        Conclusions：After 16 weeks of once- or twice-daily oral administration, treatment with the interleukin-23-receptor antagonist peptide JNJ-77242113 showed greater efficacy than placebo in patients with moderate-to-severe plaque psoriasis. (Funded by Janssen Research and Development; FRONTIER 1 ClinicalTrials.gov number, NCT05223868.).

参考来源：

[1] CDE/NMPA官网

[2] 药融云数据库

[3] FDA/EMA/PMDA

[4] 强生企业公开披露

https://www.protagonist-inc.com/；

https://www.protagonist-inc.com/publications/oral-il-23-receptor-peptide-antagonist-jnj-2113-the-journey-from-de-novo-discovery-to-phase-3-clinical-development-program；

Bissonnette R, Pinter A, Ferris LK, et al. An Oral Interleukin-23–Receptor Antagonist Peptide for Plaque Psoriasis. N Engl J Med 2024; 390:510-21；https://pubmed.ncbi.nlm.nih.gov/38324484/；

2分钟NEJM：靶向白介素-23受体的口服肽治疗斑块型银屑病;https://mp.weixin.qq.com/s?__biz=MzIxNTc4NzU0MQ==&mid=2247539188&idx=1&sn=47c57495f61e84ed8fd77ca8766cf23d&chksm=96311931d5bf41ed95d13f4ffa508175ef4ad174750297cc18f23fa8395f8f443223340dea4e&scene=27；等等。

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