Imsidolimab

伊顿健康前言银屑病治疗的研发始终围绕 “更高效、更便捷、更安全” 推进。2026 年全球管线呈现两大明确趋势：口服靶向药向高选择性迭代，进一步压低安全风险；生物制剂则持续拉长给药间隔，向半年、一年一针突破。本文基于 Psoriasis Awareness Club 发布的最新综述，盘点7款核心在研新药，看懂它们带来的疗效、给药方式上的革新。一、口服靶向药：精准迭代，安全升级Envudeucitinib（ESK-001）它是一种高选择性的TYK2变构抑制剂，它适用于中重度银屑病，推荐剂量为每日两次。 其III期 ONWARD1/2 研究显示：第 24 周 65% 的患者达到 PASI 90，40% 以上患者达到皮损完全清除（PASI 100）；48 周长期扩展研究中，持续治疗组 PASI 100 率为 54%。 该研究未观察到血脂异常、心血管事件、结核等传统 JAK 抑制剂常见风险，提示长期使用Envudeucitinib安全性明确，同时保持高水平皮损清除率。Zasocitinib（TAK-279）它也是一种变构TYK2抑制剂。它经过生物工程改造，提高了对TYK2 JH2结构域的选择性。它对TYK2的选择性比其他Janus激酶高100万倍。扎索替尼是一种口服药物，每日一次给药。一项与氘可来昔替尼头对头的III期研究显示：第16周，Zasocitinib组PASI 100 应答率达35%，是氘可来昔替尼的 2.5 倍，达到统计学优效。 Zasocitinib疗效显著优于已上市同类药物氘可来昔替尼，对 TYK2 的选择性更高，整体安全性良好，每日一次的给药方案也利于患者长期坚持。Piclidenoson它是一种A3腺苷受体激动剂，口服给药，该受体在炎症细胞中过度表达，但在正常细胞中不表达。II 期研究显示该药起效偏慢，但12周后疗效持续提升，第32周时，PASI 90的应答率达25%、PASI 100达11%；III 期 COMFORT-1 为安慰剂与阿普米司特对照研究，结果显示：3mg 每日两次的剂量，第 16 周即可实现 PASI 75 应答；2mg、3mg 每日两次两组，疗效都会随着治疗时长增加持续提升。其中 2mg 每日两次方案在第 32 周达到 PASI 75，证实疗效不劣于阿普米司特。Piclidenoson的安全性表现接近安慰剂，随治疗时间延长累积疗效显著，为不耐受传统靶向药的患者提供了更温和的长期治疗选择。二、生物制剂：超长间隔，颠覆给药模式Sonelokimab它属于纳米抗体，由 3 个可变结构域构成，其中 2 个可以牢牢结合 IL-17A 和 IL-17F，能把 IL-17A/A、IL-17F/F、IL-17A/F 这几种致病二聚体全部阻断。它的分子量大约只有 40 kDa，远小于常规单抗的 150 kDa。更小的分子，穿透能力更强，可以渗透到更深层的炎症皮损处发挥作用。 IIb 期试验可见，该药皮损清除起效快、效果持久，疗效超过部分已上市的单靶点 IL17A 抑制剂；在银屑病关节炎 III 期 IZAR1 研究里，入组时伴随皮肤损害的患者中，61% 在第 16 周达到 PASI 90。 作为纳米抗体可全面阻断各类 IL-17 致病二聚体，凭借更小分子量实现更强皮损穿透，起效迅速、清除效果持久，疗效优于部分单靶点 IL-17 抑制剂；其念珠菌感染发生率高于司库奇尤单抗，整体安全性和 IL-17 类药物一致。ORKA-001这是一款靶向 IL23p19 的人源化 IgG1 单抗。通过 Fc 工程改造，它保留了与瑞莎珠单抗相似的靶点识别能力和体外抑制效果，半衰期达到瑞莎珠单抗的 3 倍，能够持续抑制 IL23 介导的 STAT3 信号长达 24 周。 II 期 EVERLAST-A 研究显示：第16周时，63%的患者达到PASI 100，83%的患者达到PASI 90； 1期临床试验数据显示，仅单次给药600mg后，有效血药浓度可维持12个月。ORKA-001专为中重度斑块状银屑病患者设计，研发目标是实现停药后的长期病情缓解。不同于现有生物制剂需要每隔数周或数月持续打针，这款药物希望依靠长效特性，以极低频次的维持方案实现长期控病，有望把给药间隔拉长至一年一次。ORKA-002这是一款靶向 IL-17A/F 的单抗，同样有望实现半年到一年的长效给药。它经过 Fc 结构基因改造，血清半衰期可达 75–80 天。I期临床试验显示，该药物能够持续抑制IL-17，且安全性良好，未发生严重不良事件。II 期结果预计 2027 年公布。目前IL-17抑制剂通常需要每月或每两个月注射一次维持剂量，而ORKA-002的长半衰期使其只需每年注射2～3次，即可维持治疗，进一步降低 IL-17 靶点的给药频次，大幅提升患者长期治疗的依从性。Imsidolimab它是靶向 IL-36 受体的人源化 IgG4 单抗，针对泛发性脓疱型银屑病，通过阻断 IL-36 信号抗炎，感染风险较低。用药先静脉输注快速控症，之后皮下注射维持。II 期研究发现，用药第 3 天脓疱就开始消退，效果可维持至 113 天；GEMINI-1 研究中，急性发作患者第 4 周可实现皮损清除或几乎清除；长达 104 周的 GEMINI-2 研究显示，没有因严重不良反应停药的情况。填补泛发性脓疱型银屑病的靶向治疗选择，急性期静脉快速压下脓疱，后续皮下给药便于长期管理，长期安全性良好。不难看出，当前银屑病新药研发正在两条赛道同步发力：口服 TYK2 类追求疗效与安全性的平衡，长效生物制剂则向着 “更少打针、更长缓解” 突破。

iStock, nurlankani While Oppenheimer doesn’t see the Phase 3 stumble of VQW-765 as highly detrimental to Vanda Pharmaceuticals, the analyst nevertheless believes the stakes are now higher for the company’s planned Q4 readout for Nereus in GLP-1-induced vomiting. Vanda Pharmaceuticals is suspending the development of a social anxiety drug licensed from Novartis after the drug showed no significant benefit in a late-stage study. The investigational drug, called VQW-765, failed to significantly ease distress versus placebo in patients with social anxiety disorder during a social stress test, according to an announcement on Wednesday. The analysis focused on female participants, for whom the drug was previously found to be more effective. “This was a clean miss, not a near miss,” Oppenheimer analysts told investors in a Wednesday note. Vanda has decided to put the VQW-765 program on hold “pending further analysis of the full dataset,” the biotech said. The Phase 3 study, called VP-VQW-765-3201 , enrolled 546 adults with social anxiety disorder deemed to have elevated anxiety levels at baseline, as measured by validated scales. After receiving either VQW-765 or placebo, participants were asked to go through a standardized social stress test that requires them to prepare and deliver a presentation to a panel. The study’s primary outcome was distress and nervousness during the stress test in female participants, assessed using a self-reported tool, according to Vanda’s release. VQW-765 is a small-molecule partial agonist of the alpha 7 nicotinic acetylcholine receptor, the activation of which could help alleviate symptoms of anxiety and depression. Vanda picked up the drug candidate in a December 2014 settlement agreement with Novartis regarding certain disputes over the antipsychotic drug Fanapt. Alongside a $25 million equity investment, the pharma granted Vanda an exclusive worldwide license to VQW-765, which at the time was called AQW051. Phase 2 data published in July 2025 showed that patients on VQW-765 experienced lower self-reported anxiety during a standard social stress test, though the drug’s effect in the overall study population fell short of statistical significance. Stratifying by sex, results showed that VQW-765 was more effective in females, in whom the anxiety-easing effect was significant; VQW-765’s benefits in males remained non-significant. “We are disappointed that Study 3201 did not confirm the earlier Phase II findings for VQW-765 in patients with social anxiety disorder,” Vanda CEO Mihael Polymeropoulos said in a prepared statement on Wednesday. Analysts at Oppenheimer do not expect the Phase 3 miss to be highly detrimental to Vanda. VQW-765 “sat only in our bull case, so there is no change to our estimates” for the biopharma, the firm said. Oppenheimer continues to rate the biotech at outperform, suggesting it expects Vanda to deliver high returns for investors. Still, the VQW-765 pause is likely to add “pressure to the rest of the portfolio,” Oppenheimer said. Two of the three late-stage readouts the firm was keeping tabs on have already dropped, the analysts noted. The first came in September, when Hetlioz met the primary endpoint of helping patients to fall asleep faster in a Phase 3 study of delayed sleep-wake phase disorder. The second was VQW-765, a “negative” for Vanda, according to Oppenheimer. The third late-stage readout that the analysts have their eye on is for Nereus—also known as tradipitant—an oral motion-sickness drug that received approval in late December 2025. Vanda is now testing Nereus for GLP-1-induced vomiting. The biotech launched a Phase 3 trial in April, with topline data slated for the fourth quarter. Phase 2 data reported in November last year showed that tradipitant significantly lowered the proportion of patients with vomiting—the trial’s primary endpoint—as compared to placebo. The study involved 116 patients who were pretreated with tradipitant or placebo before being given a 1-mg injection of Novo’s Wegovy. Aside from the trio of late-stage readouts, Oppenheimer said Vanda’s “near-term story” will also now depend on launch execution for the schizophrenia and bipolar I disorder drug Bysanti, which notched regulatory clearance in February, and the FDA’s verdict for Quimilza in generalized pustular psoriasis expected by mid- December .