Icotrokinra

Johnson & Johnson and Protagonist Therapeutics on Monday announced favourable top-line findings from two pivotal Phase III trials, ICONIC-LEAD and ICONIC-TOTAL, evaluating its oral first-in-class IL-23-targeting peptide, icotrokinra, in patients with moderate to severe plaque psoriasis aged 12 years and older. The partners said the drug, also known as JNJ-2113, achieved the main goals in both studies, demonstrating significant skin clearance.Highlighting the fact that most patients with moderate to severe disease aren't receiving advanced therapies despite qualifying for them, Liza O'Dowd, immunodermatology disease area lead at J&J Innovative Medicine, said “icotrokinra has the potential to offer once-daily oral therapy that could help address the needs and preferences of people living with plaque psoriasis.”Notable skin clearanceThe ICONIC-LEAD study enrolled 684 participants to receive once-daily icotrokinra or placebo, the co-primary endpoints being Psoriasis Area and Severity Index (PASI) 90 and Investigator's Global Assessment (IGA) 0/1 with a minimum 2-grade improvement. Results showed that at week 16, 64.7% of icotrokinra-treated patients achieved clear or almost clear skin, ie., IGA scores of 0/1, and 49.6% achieved a PASI 90 response, compared with 8.3% and 4.4% of placebo recipients, respectively. Efficacy improved further at week 24, with 74.1% of icotrokinra recipients achieving IGA scores of 0/1 and 64.9% reaching PASI 90.Meanwhile, the partners also noted that the ICONIC-TOTAL study investigating icotrokinra versus placebo in 311 patients with psoriasis affecting special areas like the scalp, genitals, and hands/feet — met its main goal of an IGA score of 0 or 1 with at least a 2-grade improvement at week 16, underscoring the IL-23 inhibitor’s potential for addressing hard-to-treat psoriasis cases. Moreover, safety data from both studies aligned with previous Phase II findings, with similar rates of adverse events between the icotrokinra and placebo groups. The companies plan to present detailed data at upcoming medical congresses and prepare submissions for regulatory approvals.Milestone payment triggeredAs part of the 2020 research collaboration between J&J and Protagonist, the latter is set to receive $165 million in milestone payments in the first quarter of next year, which includes $115 million for a completed Phase III study, $35 million for an NDA acceptance in psoriasis, and $15 million for a Phase III initiation in another indication. Protagonist is also eligible for up to $630 million in future milestones and 6% to 10% royalties on global net sales. Protagonist CEO Dinesh Patel said the latest findings further corroborate the company’s “innovative peptide technology platform and its effectiveness in creating highly differentiated new chemical entities.”The collaborative ICONIC clinical programme also includes ICONIC-ADVANCE 1 and 2, which will assess the safety and efficacy of icotrokinra in moderate to severe plaque psoriasis against placebo and Bristol Myers Squibb's Sotyktu (deucravacitinib). Additionally, the ICONIC-PsA programme evaluating icotrokinra for psoriatic arthritis will kick off early next year, while a Phase IIb ANTHEM study for ulcerative colitis is nearing completion. Top-line readouts for ICONIC-ADVANCE 1 and 2 and ANTHEM are expected in first half of next year.J&J’s current immunology portfolio includes IL-23 blocker Tremfya (guselkumab) and dual inhibitor of IL-23 and IL-12, Stelara (ustekinumab), both approved for a range of autoimmune conditions.

11月19日，强生和Protagonist共同宣布, Icotrokinra (JNJ-2113，前称PN-235) 的关键 3 期 ICONIC 研究取得了积极的顶线结果。该3期研究在第16周达到了银屑病面积和严重程度指数（PASI）90和研究者整体评估（IGA） 的共同主要终点0/1反应，并且反应率在第24周继续改善。 据其新闻稿，JNJ-2113是第一个选择性阻断IL-23受体的靶向口服肽，适用于12岁及以上患有中度至重度斑块状银屑病（PsO）的成人和青少年。 与安慰剂相比，每日一次icotrokinra在患有中度至重度斑块状银屑病的成人和青少年中显示出显著的皮肤清除率。 在第16周时，近三分之二（64.7%） 接受埃克托白滞素治疗的患者达到0/1的 IGA 评分（皮肤透明或几乎透明），49.6% 的患者达到 PASI90，而安慰剂组分别为8.3% 和4.4%。ICONIC-TOTAL 在难治性斑块性银屑病患者中，在第 16 周实现了 IGA 评分为 0 或 1 的主要终点。 第24周时，反应率继续进一步增加，74.1% 的icotrokinra治疗患者达到0/1分，64.9%的患者达到PASI90。 安全性数据与2期FRONTIER1和2 研究一致。icotrokinra和安慰剂之间发生不良事件 （AE） 的患者比例相似，49.3% 和 49.1% 的参与者在第 16 周出现治疗中出现的不良事件（TEAE）。 ICONIC-LEAD 和 ICONIC-TOTAL 的综合结果正在准备在即将举行的医学大会上展。 ICONIC 3期临床开发计划的其他研究正在进行中，包括ICONIC-ADVANCE 1和ICONIC-ADVANCE 2，这两项研究将评估icotrokinra与安慰剂和deucravacitinib相比在中重度斑块状银屑病中的安全性和有效性。ICONIC-PsA 3 期项目将于 2025 年初启动，该项目将研究 icotrokinra 在银屑病关节炎中的治疗效果。 JNJ-2113是一款多肽口服IL-23受体拮抗剂。IL-23/IL-23R 信号通路在免疫介导的炎症性疾病包括银屑病、银屑病关节炎和炎症性肠病的发病机制中具有关键作用。 2017年，杨森斥资9.8亿美元与Protagonist Therapeutics达成协议，共同推进推进口服IL-23受体拮抗剂药物开发。2021年12月，Protagonist与杨森决定将PN-235作为候选药物。 根据Protagonist新闻稿，随着3 期 ICONIC 研究取得了积极结果，该公司已经获得杨森公司的1.65 亿美元里程碑付款。此外，Protagonist仍有资格获得高达 6.3 亿美元的未来开发和销售里程碑付款，以及全球净销售额 6-10% 的分级特许权使用费。 强生创新医学副总裁、免疫皮肤病领域负责人 Liza O'Dowd 表示：“我们很高兴看到每日一次的icotrokinra治疗取得了积极的 3 期结果，这与我们对这种首创的选择性阻断 IL-23 受体的口服靶向肽的 2 期研究一致。大多数中重度斑块状银屑病患者都符合接受先进疗法的条件，但却仍未得到治疗。Icotrokinra 有可能提供每日一次的口服疗法，有助于满足斑块状银屑病患者的需求和偏好。” “这些积极的3期研究结果证实了之前的2b期FRONTIER-1和-2研究中观察到的令人信服的疗效和安全性趋势，凸显了icotrokinra作为同类最佳口服药物的潜力，它是治疗斑块状银屑病的理想口服药物，具有显著的皮肤清除率和明显的耐受性，每天服用一次，"Protagonist公司总裁兼首席执行官Dinesh V. Patel博士说。 End 声明：本公众号所有发文章(包括原创及转载文章)系出于传递更多信息之目的，且注明来源和作者。本公众号欢迎分享朋友圈或大群，谢绝媒体或机构未经授权以任何形式转载至其他平台。 转载/商务/投稿 | 联系微信15618157102（sum_Gmi） 商务合作 稿件征集 点击了解详情 往期回顾 1 10月 | 20家生物医药裁员汇总 2 国产首款四价HPV疫苗拟纳入优先审评 3 3. 7亿美元!今年规模最大的生物医药融资诞生