A PHASE 1, OPEN LABEL, 2-PERIOD, FIXED SEQUENCE, STUDY TO ASSESS THE MASS BALANCE, ABSOLUTE BIOAVAILABILITY OF 14C PF 06826647 IN HEALTHY MALE PARTICIPANTS

The purpose of the study is to determine the metabolism and excretion following a single oral administration of 14C-PF-06826647-LR (14C labelled PF-06826647 with lower radioactivity per mass unit) in fed conditions. This information will enable assessment of clearance mechanisms of PF-06826647 as well as identify metabolites. In addition, this study will determine absolute bioavailability of PF-06826647 and understand intravenous (IV) pharmacokinetic (PK).

开始日期2020-11-10

申办/合作机构

Pfizer Inc.

NL-OMON50100 / CompletedN/A

A phase 1, open label, 2-period, fixed sequence, study to assess the mass balance, absolute bioavailability of 14C-PF-06826647 in healthy male participants - Mass balance and absolute bioavailability of 14C-PF-06826647 in men.

开始日期2020-11-10

申办/合作机构

Pfizer Inc.

NCT04209556 / Withdrawn临床2期

A PHASE 2B, RANDOMIZED, DOUBLE-BLIND, PARALLEL-GROUP, PLACEBO-CONTROLLED STUDY WITH AN OPEN LABEL EXTENSION TO EVALUATE THE SAFETY AND EFFICACY OF PF-06826647 IN PARTICIPANTS WITH MODERATE TO SEVERE ULCERATIVE COLITIS

The purpose of this study is to evaluate efficacy and safety of PF-06826647 in moderate to severe ulcerative colitis

开始日期2020-09-30

申办/合作机构

Pfizer Inc.

100 项与 Ropsacitinib 相关的临床结果

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100 项与 Ropsacitinib 相关的转化医学

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100 项与 Ropsacitinib 相关的专利（医药）

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项与 Ropsacitinib 相关的文献（医药）

2024-02-27·NEJM evidence

Brepocitinib, Zimlovisertib, and Ropsacitinib in Hidradenitis Suppurativa

Article

作者: Banfield, Christopher ; Khattri, Saakshi ; Kimball, Alexa B. ; Ghosh, Pranab ; Moiin, Ali ; Peeva, Elena ; Oemar, Barry ; Mangold, Aaron R. ; Porter, Martina L. ; Forman, Seth

BACKGROUND: Hidradenitis suppurativa (HS) is a debilitating, inflammatory skin disease with limited treatment options and partially understood pathophysiology. Using an umbrella trial design, three kinase inhibitor immunomodulators with different mechanisms of action were evaluated. METHODS: This phase 2a, double-blind, parallel-group trial enrolled adults with moderate to severe HS who were then randomly assigned (1:1:1:1) to once-daily brepocitinib 45 mg (a JAK1/TYK2 inhibitor), zimlovisertib 400 mg (an IRAK4 inhibitor), ropsacitinib 400 mg (a TYK2 inhibitor), or matching placebo for 16 weeks. The primary end point was the percentage of participants achieving HS clinical response (HiSCR) at week 16. Safety, including treatment-emergent adverse events (TEAEs), was monitored throughout. RESULTS: Totals of 52, 47, 47, and 48 participants were assigned to brepocitinib, zimlovisertib, ropsacitinib, and placebo, respectively. At week 16, 28% were lost to follow-up and assumed to be nonresponders; HiSCR occurred in 33.3% (16/48) of participants receiving placebo and in 51.9% (27/52), 34.0% (16/47), and 37.0% (17/46) of those receiving brepocitinib, zimlovisertib, and ropsacitinib (difference in percentage points vs. placebo [90% confidence interval], 18.7 [2.7 to 34.6], 0.7 [−15.2 to 16.7], and 3.5 [−12.6 to 19.6]), respectively. TEAEs occurred more frequently with active treatment (brepocitinib, 30 [57.7%]; zimlovisertib, 26 [55.3%]; ropsacitinib, 29 [61.7%]; placebo, 23 [47.9%]). Most TEAEs (infections, skin disorders, and gastrointestinal symptoms) were mild; there were no deaths. CONCLUSIONS: Participants with moderate to severe HS treated with brepocitinib experienced greater clinical response, whereas those on zimlovisertib and ropsacitinib did not, compared with placebo. These results favor the JAK/STAT pathway as an immunologic target in HS and did not confirm a role for selective IRAK4 or TYK2 inhibition. These results should be confirmed in larger studies with longer follow-up. (Funded by Pfizer; ClinicalTrials.gov registration number, NCT04092452.)

2022-08-01·JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY1区 · 医学

Oral tyrosine kinase 2 inhibitor PF-06826647 demonstrates efficacy and an acceptable safety profile in participants with moderate-to-severe plaque psoriasis in a phase 2b, randomized, double-blind, placebo-controlled study

1区 · 医学

Article

作者: Singh, Ravi Shankar P ; Gale, Jeremy D ; Peeva, Elena ; Pradhan, Vivek ; Tarabar, Sanela ; Roberts, Erika S ; Tehlirian, Christopher ; Vincent, Michael S

BACKGROUND:

Psoriasis treatments lack durable efficacy and have inconvenient administration, highlighting the need for new therapies.

OBJECTIVE:

To evaluate the efficacy and safety of tyrosine kinase 2 inhibitor, PF-06826647, in moderate-to-severe plaque psoriasis.

METHODS:

This phase 2b, double-blind study randomized participants to oral, once-daily PF-06826647 (1:1:2:2:2) 50:100:200:400 mg:placebo (16 weeks), then 200 or 400 mg (24 weeks) (NCT03895372). The primary end point was a proportion of participants achieving psoriasis area severity index (PASI) 90 at week 16. Secondary end points (PASI50/75/90/100; Physician's Global Assessment) and safety were assessed to week 40.

RESULTS:

Overall, 178 participants were treated. A significantly greater proportion of participants (risk difference % [90% CI]) achieved PASI90 in the 200-mg (33.0 [18.0, 47.1], P = .0004) and 400-mg (46.5 [30.6, 60.6], P < .0001; week 16) groups versus placebo. Significant increases from placebo were observed for all secondary end points (200 and 400 mg; weeks 6-16; P < .05); increases were evident to week 40 (categorical data). PF-06826647 was well tolerated and most treatment-emergent adverse events were mild/moderate. Eighteen participants discontinued due to treatment-emergent adverse events (14 arising from laboratory abnormalities).

LIMITATIONS:

Limitations included the large proportion of White males and non-placebo-controlled extension.

CONCLUSION:

PF-06826647 200 and 400 mg once daily showed significant efficacy versus placebo at week 16 and was well tolerated over 40 weeks.

2022-03-04·Expert review of clinical immunology

TYK2 inhibition: changing the treatment landscape for psoriasis?

作者: Gooderham, Melinda J. ; Abduelmula, Abrahim

TYK2 inhibition, changing treatment landscape for psoriasis.Psoriasis is a common immune-mediated inflammatory disease affecting approx. 2of individuals living in Western countries.The signaling of IL-23 is known to be transmitted through the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway.As TYK2 inhibitors are a relatively new treatment modality, there is not yet a com. available TYK2 inhibitor for clin. use.There are also other TYK2 inhibitors in development, such as brepocitinib (TYK2/JAK1) and PF-06826647 (TYK2/JAK2), but deucravacitinib is furthest in development and will be the focus of this editorial.Deucravacitinib is a novel, oral, selective TYK2 inhibitor with a unique mechanism of action through allosteric binding of the pseudokinase (JH2) domain which is regulatory in nature and lacks catalytic activity.Selective targeting of TYK2 results in the inhibition of signaling of IL-12, -23 and Type 1 IFN, the key cytokines involved in psoriasis pathogenesis.The overall place of deucravacitinib in the treatment of moderate-to-severe psoriasis involves multiple prescriber and patient factors, including safety, tolerability, efficacy, convenience, and impact on comorbidities.Deucravacitinib seems to check all the boxes.It has proven efficacy superior to apremilast in psoriasis, promising early phase results in psoriatic arthritis, and studies ongoing for inflammatory bowel disease.It is well tolerated with low rates of headache, nausea, and diarrhea and a favorable safety profile with low rates of AEs and no impact on laboratory parameters as seen with other JAK inhibitors.

项与 Ropsacitinib 相关的新闻（医药）

2024-12-08

·医药魔方

TYK2格局之变：中国自免玩家进击best in class

在肿瘤领域快速崛起之后，中国药企又开始围攻自免领域这片高地。近日，益方生物的TYK2变构抑制剂D-2570公布II期结果，近半数斑块状银屑病患者的皮损完全清除。银屑病口服药物的竞争格局可能要变天了。粗略来看，D-2570的整体疗效数据不仅超越现有的两款口服药物，同时可以比肩强生的口服IL-23R拮抗剂JNJ-2113，摸到了best in class分子的门槛。银屑病领域代表性口服药物II期研究数据注：PASI为银屑病面积及严重指数，用于记录患者的皮肤红肿程度、鳞屑厚度和范围、瘙痒程度等表现，以评估病情和药物疗效。PASI 75指评分降低75%及以上，PASI 90和PASI 100以此类推。 D-2570是中国药企在自免领域开始突围的一个例证。凭借极强的跟随策略以及不断进化的创新能力，国内药企已渗透布局JAK、CD19、IL-17、TNF-α和PDE等大多数热门自免靶点赛道，覆盖银屑病、特应性皮炎、慢性阻塞性肺病（COPD）等大病种，一些潜在BIC分子开始出现。在火热的出海潮中，国产自免新药也开始成为跨国药企的掘金地。海内外自免领域的研发落差，正逐步缩小。 TYK2抑制剂格局将变由于病因复杂，银屑病药物的口服治疗难题一直未得到圆满解决。从“银屑病（psoriasis）”第一次被正式报道[1]到现在已经过去200多年的时间，然而迄今为止仅有两款口服药物——阿普米司特（PDE4抑制剂）和氘可来昔替尼（TYK2变构抑制剂）成功上市，这足以说明口服银屑病药物开发壁垒突破之难。虽然阿普米司特是率先破局的选手，在银屑病领域已有十年应用历史，但是这款药物的疗效并不算突出，与IL-17A抗体等生物制剂相比有一定的差距。另一个不足之处是，阿普米司特的用药频率为每日2次，并且需要剂量滴定，对患者来说还不够便利。阿普米司特的作用机制是迂回式的，通过抑制PDE4干扰部分炎症细胞的活动来间接减少促炎因子的分泌，区别于细胞因子抑制剂的“正面硬刚”式打法。这也许是阿普米司特疗效欠佳的原因。阿普米司特疗效不足给TYK2抑制剂接棒冲刺银屑病口服治疗难关留下了想象空间。药物研发者们已经在TYK2的家族成员JAK1/2/3身上进行过多次尝试，但因无法实现高选择性抑制而疗效平平。直到有研究报道TYK2是调控关键细胞因子IL-17和IL-23响应的关键角色，让选择性抑制TYK2成为银屑病口服药物新的突围方向。 TYK2信号轴和JAK1/2/3信号轴区别[2] TYK2抑制剂的研发方向分为竞争性抑制剂和变构抑制剂，前者选择与ATP竞争结合催化位点（JH1结构域）以降低TYK2被激活的概率，而后者选择结合变构位点（JH2结构域）以断绝ATP激活TYK2的可能。竞争性抑制剂的缺点在于总有“漏网之鱼”可以活化TYK2，从这一点来看，可以将ATP结合TYK2的可能扼杀在摇篮之中的变构抑制剂更有优势。百时美施贵宝在TYK2赛道第一个闯关成功——氘可来昔替尼在2022年通过了FDA的审批考验。氘可来昔替尼作为一款每日1次使用的口服药物，在用药便利性上已经有所提升，但是疗效仍然不如生物制剂，也给后来者留下了优化空间银屑病治疗图景[3] 作为JAK抑制剂的资深玩家，辉瑞也在TYK2靶点有过尝试，但其选择的是竞争性抑制剂的开发策略。 Ropsacitinib（PF-06826647）对斑块状银屑病的治疗效果还算不错，在PASI 75指标上可以与安慰剂拉开61%的差距，与氘可来昔替尼在II期研究中的表现相近。遗憾的是，Ropsacitinib作为一款TYK2竞争性抑制剂，无法避开对JAK的影响，导致其安全性风险较高[4]。目前，辉瑞已放弃推进开发Ropsacitinib的银屑病适应症，转而探索对其他自免疾病的治疗潜力。中国药企对优化TYK2抑制剂的热情极高，全球几乎一半（23/50）的TYK2抑制剂来自于中国，也有多款国产TYK2抑制剂披露过临床数据，其中ESK-001（海思科）的权益已被转移至海外药企Alumis手中。从疗效数据来看，ESK-001治疗斑块状银屑病在高剂量下与氘可来昔替尼相当；HS-10374（翰森制药）和ICP-488（诺诚健华）的II期研究数据还没有表现出成为超越氘可来昔替尼的BIC分子的潜力。益方生物的D-2570在斑块状银屑病上的II期数据首次帮助中国药企在TYK2抑制剂赛道上跑赢海外药企。数据显示，口服D-2570治疗12周后，85%-90%的患者可以达到PASI 75，70.7%-77.5%的患者可以达到PASI 90，39%-50%患者可以达到PASI 100。这样的数据已经远超同赛道选手，并且接近生物制剂的疗效。口服银屑病赛道仍然有很大的想象空间。在自免领域的火热发展之下，随着更多的国产TYK2抑制剂公布临床数据，或许这一赛道也将成为海外药企挖掘宝藏的目标。中国玩家打响自免突围赛国产TYK2抑制剂的突破，其实也是中国药企在自免领域开始突围的一个缩影。在全球细分疾病药物市场中，自免领域所占的份额仅次于肿瘤，持续孕育出阿达木单抗、度普利尤单抗和乌司奴单抗这些百亿美元分子，也成就了艾伯维、赛诺菲和强生等自免巨头。与海外玩家进击自免的一派火热形成鲜明对比的是，聚焦该领域的国内企业并不多，研发实力还比较薄弱，但这种情况正在悄然转变。通过跟随式开发策略，国内药企已经迅速渗透JAK、CD19、IL-17、TNF-α和PDE等大部分热门自免靶点赛道，覆盖了银屑病、特应性皮炎、COPD等大病种，而在TYK2、IL-4Rα、TSLP、IL-12p40等靶点上还涌现了研发进度全球前3或前5的国产自免新药分子。从供给端开始，国内外自免领域的研发差距逐渐缩小。比如IL-17赛道，全球共有69款在研产品，其中由中国企业原研开发的有33个，近乎占据半壁江山，而且已经有一些成果产出。在今年8月，恒瑞医药的夫那奇珠单抗和智翔金泰的赛立奇单抗于同一天获批上市，一举打破同类进口药物的长期独占局面，为中国银屑病患者带来治疗新选择。长久以来，国内自免市场其实还没被很好地开发，即便近年来有进口的自免药物陆续进入中国市场，但由于药品定价、疾病认知、治疗意识等现实因素，患者用药的可及性和依从性仍有待提升，这也是国内企业挖掘存量和增量空间的机会。在度普利尤单抗统治的IL-4Rα赛道，国内药企也正迎头赶上。石药集团/康诺亚的司普奇拜单抗突破在前，于今年9月获批上市，在同类中拿下全球第2的名次；紧随其后还有8款处于临床III期阶段的国产IL-4Rα单抗。无法否认，国内玩家在某些自免领域已有扎堆内卷之势，但也正是通过内卷的洗礼，中国创新才得以快速成长，进而蜕变出了全球竞争力，有了更多的出海场景。就以TSLP赛道而言，全球仅有安进/阿斯利康的tezepelumab一款获批上市。近日，博奥信/正大天晴的BSI-045B（TQC2731）率先在国内启动了治疗哮喘的III期临床，这是国内首款、全球第2款进入III期阶段的TSLP单抗。已有海外伙伴认可BSI-045B的潜力。在今年11月，Aclaris Therapeutics从博奥信引进了该药物在内的两款TSLP靶向药物。据新闻稿介绍，另一款合作药物BSI-502是一种处于临床前的潜在BIC新型TSLP/IL-4R双抗。交易公布当天，Aclaris Therapeutics股价即大涨53%。恒瑞的TSLP单抗SHR-1905（AIO-001）在更早时候出海，而后又被跨国药企收入囊中。2023年11月，Aiolos Bio以2500万美元首付款拿到SHR-1905除大中华区外的全球独家权益，公司创始人认为SHR-1905是该赛道“潜在的游戏规则改变者”。在增强效力和延长半衰期的技术加成下，SHR-1905有望实现每6个月给药一次，可能重新定义护理标准；Tezepelumab则是每4周给药一次。紧接着，在今年1月，Aiolos Bio被GSK以10亿美元首付款收购，核心原因就是看中了其唯一管线SHR-1905，GSK认为该药物具有BIC潜力。透过海外公司的动作，我们能进一步清晰地感知到，中国企业完全有能力在自免领域打造出真正差异化的创新药物，而非仅陷于低层次内卷。近期国产自免T细胞衔接器（TCE）的出海潮，也是很好的佐证。这些播撒的青苗种子，相信有不少会迎来收获的那一天。 - 上下滑动查看参考资料 - [1]Robert Willan MD FRS (1757-1812): dermatologist of the millennium. Journal of the Royal Society of Medicine. 1999. 92(6):313–318. [2]Novel Therapies in Plaque Psoriasis: A Review of Tyrosine Kinase 2 Inhibitors. Dermatol Therapy. 2023. 13:417–435. [3]https://irp.cdnwebsite.com/8e9b9820/files/uploaded/PTGX_Corp%20Deck_3.7.23%20FINAL%20for%20upload__.pdf [4]Oral tyrosine kinase 2 inhibitor PF-06826647 demonstrates efficacy and an acceptable safety profile in participants with moderate-to-severe plaque psoriasis in a phase 2b, randomized, double-blind, placebo-controlled study. Journal of The American Academy of Dermatology. 2022. 87(2):333-342. 推荐阅读强生正中靶心背后，银屑病赛道的变局千亿美元自免赛道，中国创新药新风口 MNC深耕的自免赛道，国内企业谁能拔得头筹？ Copyright © 2024 PHARMCUBE. All Rights Reserved. 欢迎转发分享及合理引用，引用时请在显要位置标明文章来源；如需转载，请给微信公众号后台留言或发送消息，并注明公众号名称及ID。免责申明：本微信文章中的信息仅供一般参考之用，不可直接作为决策内容，医药魔方不对任何主体因使用本文内容而导致的任何损失承担责任。精彩预告线上直播 ↑点击扫码，直达直播间↑

临床2期

2023-11-27

·FierceBiotech

Roivant ends longshot lupus program after phase 2 fail

Priovant, which is keeping the specific data to itself for now, had hoped the phase 2 study would set it up to seek approval for brepocitinib in lupus. Roivant’s CEO Matt Gline always knew the lupus drug brepocitinib was a longshot: “Anybody who is not afraid of a lupus study is an idiot, you shouldn’t trust them,” he told Fierce Biotech at the beginning of the year. Now, it seems Gline’s fear was warranted. The therapy, snagged from Pfizer in 2022, did not lead to improvement in lupus disease activity at week 52, failing the main goal of a phase 2 study. Roivant’s Priovant unit will now drop the indication but continue with brepocitinib in a handful of other conditions including non-infectious uveitis (NIU). Gline blamed the failure on high placebo response in the trial, according to a statement. Brepocitinib was tested in adult patients with moderate to severe active systemic lupus erythematosus. Efficacy was measured using a common scale for lupus called the Systemic Lupus Erythematosus Responder Index change of 4 (SRI-4). “We saw some of the highest SRI-4 responder rates ever observed in a lupus study in the active arm of this trial, along with a favorable safety and tolerability profile,” Gline said in the Monday release. “Unfortunately, we also saw the highest placebo response rate observed in any significant SLE study, and as such it was not possible to truly assess the impact of the drug, or to establish sufficient differentiation from other therapies in lupus patients.” Roivant formed the company Priovant around brepocitinib and another TYK2 inhibitor called PF-06826647, or ropsacitinib, last year in a deal with Pfizer. The Big Pharma holds a 25% stake in Priovant. Priovant, which is keeping the specific data to itself for now, had hoped the phase 2 study would provide the data needed to seek an approval in lupus for brepocitinib. Now, the company will turn to the rest of the brepocitinib program. The TYK2 inhibitor is being tested in a phase 2 trial for NIU with a readout expected in the first quarter of 2024. A phase 3 readout in dermatomyositis is expected sometime in 2025. Roivant said that brepocitinib has also demonstrated potential benefit in six placebo-controlled mid-phase studies in psoriasis, psoriatic arthritis, alopecia areata, hidradenitis suppurativa, ulcerative colitis and Crohn’s disease. Gline said today’s results show that brepocitinib “is a highly active agent with a good safety profile.” Roivant is just the latest company to be stymied by lupus. Horizon Therapeutics, which was bought out by Amgen in October, suffered a phase 2 failure in July as well. Amgen also cut two of its own programs earlier this year, as did Eli Lilly.

临床2期并购临床3期临床失败临床结果

2023-03-21

·Insight数据库

武田 40 亿美元首付款引进 TYK2 抑制剂挺进 III 期临床，直追 BMS？

近日，武田宣布其在研 TYK2 抑制剂 TAK-279（NDI-034858）治疗中至重度斑块型银屑病的 2b 期临床达到主要终点和次要终点。在 12 周时，与安慰剂组相比，5mg、15mg 以及 30mg TAK-279 组实现 PSAI-75、90、100 的患者比例均有显著改善。基于该项 2b 期研究结果，武田计划将于 2023 财年启动一项 TAK-279治疗银屑病的 III 期临床试验。来自：武田官网武田 TYK2 抑制剂 II 期临床积极该项 2b 期研究共纳入了 259 名患者，并以 1:1:1:1:1 的比例随机分配每天一次接受四种剂量的 TAK-279 或安慰剂中的一种，持续 12 周。结果显示：与安慰剂组（6%；p<0.001）相比，TAK-279 组患者达到 PASI 75 的比例明显更高（分别为 44%、68%、67%；5 mg、15 mg、30 mg），达到主要研究终点。与安慰剂组（0%；p<0.001）相比，达到 PASI 90 的 TAK-279 患者比例明显更高（分别为 21%、45%、46%；5 mg、15 mg、30 mg）；而达到 PASI 100 比例分别 10%、15%、33%（5 mg、15 mg、30 mg）对比安慰剂（0%；30 mg 时 p<0.001）。TAK-279 为武田在去年 12 月以 40 亿美元的首付款从 Nimbus Therapeutics 引进的一种口服选择性变构酪氨酸激酶 2 (TYK2) 抑制剂。从疗效数据来看，最高剂量 30mg TAK-279 组中 67% 的患者达到了 PASI 75，46% 患者达到 PASI 90，而有 33% 的患者达到了完全的皮肤清除率（ PASI 100）。而 BMS Deucravacitinib III 期临床研究（POETYK-PSO-1、POETYK-PSO-2）数据显示：第 16 周时 Deucravacitinib（6mg）组 PASI 75 患者比例达 58.7% 和 53.6%；PASI 90 的比例则分别为 36%（POETYK PSO-1）和 27%（POETYK PSO-2）；简单的从这两者数值来看（并非头对头），TAK-279 具有明显的优势，不过若与 Deucravacitinib II 期研究结果相比，优势似乎并不明显。在 IM011-011 试验中，在接受剂量为每次 3 mg，每日 2 次或更大剂量 BMS-986165 的患者组中，PASI 75 患者比例达 67%-75%；PASI 90 达到 43%-44%，PASI 100 也有 9%-25% 的患者。不过，武田似乎押注 TAK-279 在 III 期试验中能达到与 IIb 期相同的疗效。BMS Deucravacitinib（氘可来昔替尼/Sotyktu）为全球首款且当前唯一一款获批上市的 TYK2 抑制剂，于去年 9 月获 FDA 批准用于治疗成人中至重度斑块状银屑病。据 BMS 预计 deucravacitinib 年度销售额峰值将达 40 亿美元。来自：BMS 官网去年 5 月，BMS 在欧洲皮肤病学会（EADV）春季研讨会上公布了 POETYK PSO 长期扩展试验（POETYK PSO-LTE）的两年结果，进一步证实氘可来昔替尼治疗成人中重度斑块状银屑病兼具持久的疗效与一致的安全性。据 Insight 数据库显示，Deucravacitinib 目前共登记有 50 多项临床试验。除银屑病外，也在拓展红斑狼疮、克罗恩病、溃疡性结肠炎等适应症。在国内，针对克罗恩病、狼疮性肾炎的研究已进入 II 期临床阶段。Deucravacitinib 项目全球开发进展来自：Insight 数据库全球 39 款在研！国内百济、诺诚健华已入局当前已上市的两代 JAK 抑制剂主要抑制 JAK1、JAK2 以及 JAK3，然而不管是一代还是二代仍存在一些潜在副作用。如，一代的托法替尼等有「泛 JAK」现象，二代的乌帕替尼等有血栓风险。因此，很多企业将目光转向了同为 JAK 激酶家族成员的 TYK2。TYK2 参与多种细胞因子 IL-23、IL-12、I 型 IFN 的信号传导，并介导下游的 STAT 磷酸化。在银屑病等多种免疫介导的疾病中作为细胞因子信号通路的关键调节因子发挥作用。据 Insight 数据库显示，当前全球共有 39 款 TYK2 抑制剂在研，其中已进入临床阶段的有 15 款，详见下图。*PS：1）下文只讨论该靶点高选择性抑制 TYK2 的在研产品，不包括 JAK1/TYK2、JAK3/TYK2 双分子抑制剂；2）表格为人工整理，如有纰漏，请指正。来自：Insight 数据库除 Deucravacitinib 外，针对 TYK2 靶点，BMS 还布局了另外两款产品 BMS-986020、BMS-986322，可见其对该靶点的重视程度。两者均已进入 II 期临床阶段。除 BMS 外，辉瑞的 TYK2 抑制剂 PF-06826647（Ropsacitinib）针对化脓性汗腺炎、斑块状银屑病以及溃疡性结肠炎的研究均处于 II 期临床阶段。在国内，PF-06826647 以溃疡性结肠炎适应症为先，相关临床试验申请已于 2020 年 7 月获批。辉瑞 PF-06826647 全球开发进度甘特图来自：Insight 数据库网页版（http://db.dxy.cn/v5/home/）而在国内，共有 5 款 TYK2 抑制剂进入临床阶段，除辉瑞 PF-06826647、BMS Deucravacitinib 外，诺诚健华、百济也有布局。去年 4 月，据 Insight 数据库，百济神州首次在国内登记启动了一项 BGB-23339 的国际多中心 I 期临床试验（登记号：CTR20220705），今年 2 月已完成该项研究。而针对斑块状银屑病，已于去年 3 月在国内获批临床（受理号：CXHL2101726）。CTR20220705 试验历史时光轴来自：Insight 数据库网页版（http://db.dxy.cn/v5/home/）诺诚健华则有 ICP-488、 ICP-332 两款产品进入临床阶段。来自：Insight 数据库网页版免责声明：本文仅作信息分享，不代表 Insight 立场和观点，也不作治疗方案推荐和介绍。如有需求，请咨询和联系正规医疗机构。编辑：HebePR 稿对接：微信 insightxb投稿：微信 insightxb；邮箱 insight@dxy.cn点击卡片进入 Insight 小程序国内审评进度、全球新药开发…随时随地查！多样化功能、可溯源数据……Insight 数据库网页版等你体验点击阅读原文，立刻解锁！

临床3期临床2期引进/卖出临床成功临床结果

100 项与 Ropsacitinib 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
溃疡性结肠炎	临床2期	美国	Pfizer Inc.	2020-09-30
化脓性汗腺炎	临床2期	美国	Pfizer Inc.	2019-12-02
化脓性汗腺炎	临床2期	澳大利亚	Pfizer Inc.	2019-12-02
化脓性汗腺炎	临床2期	加拿大	Pfizer Inc.	2019-12-02
斑块状银屑病	临床2期	美国	Pfizer Inc.	2019-06-27
斑块状银屑病	临床2期	日本	Pfizer Inc.	2019-06-27
斑块状银屑病	临床2期	加拿大	Pfizer Inc.	2019-06-27
斑块状银屑病	临床2期	波兰	Pfizer Inc.	2019-06-27

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04092452 (Pubmed \| NEJM Evid) 人工标引	临床2期	化脓性汗腺炎 JAK1 \| TYK2	194	zimlovisertib	壓壓鬱構醖鹹艱蓋顧觸(願選齋獵鹽範顧網鹽醖) = 積艱遞衊觸襯積選糧壓積憲範鹽蓋獵願鹽淵鏇 (餘獵糧壓餘蓋憲蓋衊壓 ) 更多	积极	2024-02-27
NCT04092452 (CTgov)	临床2期	化脓性汗腺炎	194	placebo+PF-06826647+PF-06700841+PF-06650833 (Placebo)	顧艱顧膚網艱餘鹹鏇膚(淵糧製繭壓觸顧範餘選) = 糧齋製網構衊願淵遞齋夢願獵範繭淵鹹膚醖窪 (衊觸壓鏇積範膚選餘鑰, 襯蓋窪積膚簾製獵觸齋 ~ 蓋積鏇築齋糧鬱廠繭襯) 更多	-	2023-06-15
NCT04092452 (CTgov)	临床2期	化脓性汗腺炎	194	PF-06650833 (PF-06650833 400mg QD)	顧艱顧膚網艱餘鹹鏇膚(淵糧製繭壓觸顧範餘選) = 憲衊構廠鬱餘憲膚構餘夢願獵範繭淵鹹膚醖窪 (衊觸壓鏇積範膚選餘鑰, 製選膚繭構蓋鹹構衊鏇 ~ 顧簾顧鏇願顧顧艱選製) 更多	-	2023-06-15