排名前五的靶点	数量

MEK(双特异性丝裂原活化蛋白激酶激酶)	1
Opioid receptors(阿片样受体)	1
M1 receptor x M3 receptor	1
EGFR(表皮生长因子受体erbB1)	1
IL-6(白细胞介素-6)	1

关联

项与 R-Pharm JSC 相关的药物

Nemonoxacin Malate

苹果酸奈诺沙星

靶点

Bacterial DNA gyrase x Topoisomerase IV

作用机制

细菌DNA旋转酶复合体抑制剂 [+1]

在研机构

原研机构

在研适应症

非在研适应症

最高研发阶段批准上市

首次获批国家/地区

中国

首次获批日期2016-05-27

Imidafenacin

咪达那新

靶点

M1 receptor x M3 receptor

作用机制

M1 receptor拮抗剂 [+1]

在研机构

Eisai Co., Ltd. [+5]

原研机构

KYORIN Pharmaceutical Co., Ltd.

在研适应症

膀胱过度活动症 [+2]

非在研适应症-

最高研发阶段批准上市

首次获批国家/地区

日本

首次获批日期2007-04-18

Odelepran

靶点

Opioid receptors

作用机制

Opioid receptors拮抗剂

在研机构

R-Pharm Overseas, Inc.

原研机构

Eli Lilly & Co.

在研适应症

酗酒

非在研适应症-

最高研发阶段申请上市

首次获批国家/地区-

首次获批日期-

项与 R-Pharm JSC 相关的临床试验

NCT05107934 / Suspended临床2/3期

International, Double-blind, Randomized, Placebo-controlled Study to Evaluate the Efficacy and Safety of RPH-104 Treatment in Patients With Recurrent Pericarditis

The primary purpose of this study is the evaluation of the efficacy and safety of RPH-104 treatment in patients with recurrent pericarditis.
Pharmacokinetic and pharmacodynamic parameters of RPH-104 multiple doses in this patient population will be assessed as well.

开始日期2025-12-01

申办/合作机构

R-Pharm Overseas, Inc.

[+2]

NCT04213274 / Withdrawn临床2期

A Randomized, Double-Blind, Placebo-Controlled, Multicenter, Phase 2 Study of the Efficacy and Safety of RPH-104 in Adult Subjects With Schnitzler Syndrome

The primary goal of the study is to assess the efficacy and safety of RPH-104 in subjects with Schnitzler Syndrome using Schnitzler Disease Activity Score (SDAS), which includes the Physician's Global Assessment (PGA) and the local laboratory C-reactive protein (CRP) result

开始日期2023-05-01

申办/合作机构

R-Pharm Overseas, Inc.

[+1]

NCT05773170 / CompletedN/A

Retrospective Registry for the Efficacy and Safety Evaluation of Refralon®, Concentrate for Solution for Intravenous Injection in Patients With Paroxysmal and Persistent Atrial Fibrillation and Flutter

The goal of this retrospective registry is to evaluate the efficacy and safety of Refralon®, concentrate for solution for intravenous injection, as chemical cardioversion in patients with paroxysmal and persistent atrial fibrillation and flutter in routine clinical practice. The main questions it aims to answer are:
What is the incidence of sinus rhythm restoration within 6 hours in patients with paroxysmal atrial fibrillation (AF)/atrial flutter (AFL) after the first dose of Refralon®?
What is the incidence of sinus rhythm restoration within 24 hours in patients with persistent AF/AFL after the first dose of Refralon®?

开始日期2022-11-11

申办/合作机构

R-Pharm JSC

100 项与 R-Pharm JSC 相关的临床结果

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0 项与 R-Pharm JSC 相关的专利（医药）

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项与 R-Pharm JSC 相关的文献（医药）

2024-08-13·CIRCULATION

Results of International, Double-Blind, Randomized, Placebo-Controlled, Phase IIa Study of Interleukin-1 Blockade With RPH-104 (Goflikicept) in Patients With ST-Segment–Elevation Myocardial Infarction (STEMI)

Letter

作者: Pereverzeva, Kristina ; Fedash, Andrey ; Staroverov, Ilya ; Novosadov, Vladimir ; Popov, Nikolay ; Meray, Imad ; Golino, Michele ; Rozanov, Denis ; Thomas, Georgia ; Turlington, Jeremy S. ; Mekhriakov, Sergei ; Yakushin, Sergey ; Agirov, Murat ; Lapin, Oleg ; Privalova, Olga ; Bogin, Vlad ; Zubova, Ekaterina ; Kotova, Anastasia ; Pisaryuk, Alexandra ; Selezneva, Natalia ; Seleznev, Sergey ; Talasaz, Azita H. ; Egorova, Alina N. ; Buono, Marco Giuseppe Del ; Zyuryaev, Ilya ; Lavrovsky, Yan ; Kalashnikov, Igor ; Mayorov, Vyacheslav ; Ivanova, Galina ; Abbate, Antonio ; Privalov, Dmitry V. ; Kalimulin, Denis ; Pevzner, Dmitry V. ; Babaeva, Lala ; Cremer, Paul C. ; Kornilov, Egor ; Savelieva, Ekaterina ; Lonchakova, Oxana ; Van Tassell, Benjamin ; Marawan, Amr ; Damonte, Juan Ignacio ; Taylor, Angela ; Nilk, Rostislav ; Duhanina, Ekaterina ; Grishin, Sergey A. ; Samsonov, Mikhail Yu ; Pravkina, Ekaterina ; Markley, Roshanak ; Shogenov, Zaur ; Osmanova, Samra ; Safarian, Vakhtang ; Yurkovskiy, Andrey ; Ponomar, Ekaterina G.

2023-07-01·Journal of the American College of Cardiology

Treatment of Idiopathic Recurrent Pericarditis With Goflikicept

Article

作者: Moiseeva, Olga M ; Myachikova, Valentina Yu ; Abbate, Antonio ; Egorova, Alina N ; Samsonov, Mikhail Yu ; Maslyanskiy, Alexey L ; Schedrova, Margarita L ; Lavrovsky, Yan ; Gleykina, Ekaterina V ; Grishin, Sergey A ; Vinogradova, Oksana V

BACKGROUND:

Idiopathic recurrent pericarditis (IRP) is a rare autoinflammatory disease. Interleukin (IL)-1α and IL-1β are the pivotal cytokines in the pathophysiology of acute pericarditis and its recurrence. We created a phase II/III study with a new IL-1 inhibitor-goflikicept in IRP.

OBJECTIVES:

This study sought to evaluate the efficacy and safety of goflikicept treatment in patients with IRP.

METHODS:

We conducted a 2-center open-label study of goflikicept in patients with IRP with and without recurrence at time of enrollment. The study consisted of 4 periods: screening, run-in (open-label treatment period), randomized withdrawal, and follow-up. Patients with clinical response to goflikicept in the run-in period were randomized (1:1) to a placebo-controlled withdrawal period, where the time to first pericarditis recurrence (primary endpoint) was evaluated.

RESULTS:

We enrolled 22 patients, and 20 of these patients were randomized. Reduction of C-reactive protein level accompanied by reduction of chest pain and pericardial effusion compared to baseline was demonstrated during the run-in period. Recurrence of pericarditis occurred in 9 of 10 patients in the placebo group, and there were no recurrence events in goflikicept group within 24 weeks after randomization (P < 0.001). A total of 122 adverse events were reported in 21 patients (95.5%), with no deaths and no new safety signals identified for goflikicept.

CONCLUSIONS:

Treatment with goflikicept prevented recurrences and maintained IRP remission with a favorable risk-benefit ratio. Goflikicept reduced the risk of recurrence compared with placebo. (Study to Evaluate the Efficacy and Safety of RPH-104 Treatment in Patients With Idiopathic Recurrent Pericarditis; NCT04692766).

2017-04-01·Journal of clinical psychopharmacology

5-HT6 Receptor Antagonist as an Adjunct Treatment Targeting Residual Symptoms in Patients With Schizophrenia

Article

作者: Potanin, Sergey ; Morozova, Margarita ; Ivaschenko, Alexander ; Lepilkina, Taissia ; Beniashvili, Allan ; Vostokova, Natalia ; Burminskiy, Denis ; Lavrovsky, Yan ; Rupchev, George

Abstract:

Background:

Treating patients who experience residual psychotic symptoms during remission of schizophrenia remains one of the most challenging problems. The mechanisms underlying these symptoms differ from those of acute hallucinations and delusions. 5-HT6 receptor antagonists have been considered promising agents in treatment of residual psychotic symptoms and cognitive dysfunction. The aim of the study was to assess the efficacy of a selective 5-HT6 inhibitor Avisetron in the reduction of residual psychotic symptoms in patients with schizophrenia on stable antipsychotic therapy.

Methods:

Eighty clinically stable outpatient subjects with schizophrenia with residual psychotic symptoms were randomized in a double-blind manner to 6 weeks of Avisetron or placebo at 1:1 ratio. Subjects received 8 mg of Avisetron or placebo on top their stable antipsychotic treatment. Standard clinical scales and cognitive tests were used for endpoint assessment. The primary efficacy endpoint was the mean reduction of total Positive and Negative Syndrome Scale score after 6 weeks of treatment.

Results:

No significant differences in the primary and secondary endpoints were found between the groups. However, based on the subgroup analysis, the significant improvement of total Positive and Negative Syndrome Scale score and residual psychotic symptoms was observed in female patients.

Conclusions:

It was a negative study with unexpected benefits of the drug only in females. We hypothesized that the role of patients' sex can impact the treatment response to serotonergic drugs in general. We suggest a possible synergistic interaction between estrogen and Avisetron by means of modulating the effect of estrogens on the serotonergic system. Future studies targeting the sex-related effects of serotonergic drugs are warranted.

项与 R-Pharm JSC 相关的新闻（医药）

2024-10-18

·BiG生物创新社

盘点｜自免重磅靶点及研发进展

作者｜小麦目前自免是仅次于肿瘤的第二大市场领域，2022年全球自免药物市场规模约达1323亿美元，据弗若斯特沙利文预测，到2030年，全球自免药物市场规模有望达到1760亿美元，2022~2030年复合年增长率为3.6%。国内在自免领域远远落后于国外，但近几年国内自免药物发展迅速，今年迪哲医药的JAK抑制剂戈利昔替尼、康诺亚生物的IL-4Rα抗体药物司普奇拜单抗、恒瑞医药的靶向IL-17A生物制剂夫那奇珠单抗和智翔金泰的靶向IL-17A生物制剂赛立奇单抗等相继获批上市，有望打破进口药的垄断地位，给患者提供更多的选择。 01 JAK靶向制剂 JAK激酶属于细胞内非受体酪氨酸激酶家族，包括JAK1、JAK2、JAK3、TYK2四个成员，介导细胞因子产生的信号，并通过JAK-STAT信号通路传递下去，参与了免疫、细胞分裂、细胞死亡和肿瘤形成等过程。该通路异常可能导致各种疾病，如皮肤病、癌症和影响免疫系统的疾病等（图1）[1]。图1. JAK家族介导信号通路全球已有十多款JAK抑制剂获批上市，包括第一代的托法替布、芦可替尼、巴瑞替尼、培非替尼和迪高替尼；第二代的菲达替尼、乌帕替尼、非戈替尼、阿布昔替尼和帕瑞替尼以及第三代的氘可来昔替尼等，这些抑制剂大多用于关节炎、特应性皮炎等自免疾病（图2）。图2. 获批和部分在研的JAK抑制剂为了提高竞争力，很多药企开始探索JAK抑制剂的新用途，如辉瑞的利特昔替尼、礼来巴瑞替尼和Concert Pharmaceuticals/Sun Pharmaceuticals的氘代芦可替尼获批斑秃新适应症，迪哲医药的戈利昔替尼获批用于治疗既往至少接受过一线系统性治疗的复发或难治的外周T细胞淋巴瘤（r/r PTCL）成人患者，成为全球首个且唯一获批用于治疗PTCL的JAK1抑制剂。除此之外，还有很多临床在研的JAK抑制剂，如泽璟制药的杰克替尼、恒瑞医药的艾玛昔替尼、辉瑞/Priovant Therapeutics的brepocitinib和再极医药的MAX-40070等，其中杰克替尼和艾玛昔替尼都处于申报上市阶段。 02 IL-4靶向制剂白细胞介素4（IL-4）主要是由T细胞、自然T细胞、肥大细胞和嗜酸性粒细胞产生的一种糖基化的I型细胞因子。 IL-4和IL-13是2型免疫反应中的关键细胞因子，作用于1型 IL-4Rα/γ和/或2型IL-4Rα/IL-13Rα复合物引发其信号传导作用，从而激活JAK-STAT信号通路（图3）。图3. IL-4和IL-13介导的信号通路目前为止全球范围内有5款靶向IL-4R药物获批上市，分别是甲磺司特、度普利尤单抗、吡美莫司、Actimmune以及司普奇拜单抗，其中度普利尤单抗是全球首款获批的IL-4R单抗药物，司普奇拜单抗是国内首个、全球范围第二个申报并获批上市的IL-4Rα抗体药物。图4. 获批和部分在研的靶向IL-4的药物度普利尤单抗是赛诺菲的当家花旦，在自免领域尤其是特应性皮炎适应症上取得巨大成功，撑起特药板块半边天，2023年销售额达到107.15亿欧元（115.7亿美元）。今年7月和9月，度普利尤单抗相继在欧盟、美国和中国获批慢性阻塞性肺病（COPD）新适应症，扩大其适应人群。除此之外，临床上还有很多在研的IL-4/IL-4R抑制剂，如康乃德的CBP-201、康方生物的AK120以及智翔医药的GR-1802等。 03 IL-17靶向制剂白细胞介素17（IL-17）是由CD4+ T细胞分泌，能够诱导上皮细胞、内皮细胞、成纤维细胞合成分泌IL-6、IL-8、G-CSF、PGE2，促进ICAM-1的表达的促炎因子。 IL-17有 IL-17A、IL-17B、IL-17C、IL-17D、IL-17E（也被称为IL-25）和IL-17F 6个家族成员。白介素IL-17受体（IL-17R）有IL-17RA、IL-17RB、IL-17RC、IL-17RD、IL-17RE 5个家族成员（图5）[2]。图5. IL-17介导的信号通路全球范围内共上市7款靶向IL-17A/IL-17RA药物，分别是司库奇尤单抗、依奇珠单抗、尼塔奇单抗、比吉利珠单抗、布罗利尤单抗、夫那奇珠单抗和赛立奇单抗（图6）。图6. 获批和部分在研的靶向IL-17药物目前，司库奇尤单抗和依奇珠单抗是全球最畅销的两款IL-17靶向生物制剂，司库奇尤单抗是由诺华研发的首款获批上市的靶向IL-17A单抗，用于治疗银屑病、银屑病关节炎和强直性脊柱炎等自免疾病，2022年销售额达47.88亿美元，2023年销售额达49.8亿美元。依奇珠单抗是由礼来研发的靶向IL-17A单抗，是第一个在银屑病关节炎（PsA）头对头研究中疗效优于阿达木单抗的IL-17A拮抗剂，2022年销售额达到24.82亿美元，2023年销售额达到27.6亿美元。今年8月份，恒瑞医药的夫那奇珠单抗和智翔金泰的赛立奇单抗获批上市，用于治疗适合接受系统治疗或光疗的中重度斑块状银屑病成人患者，成为国产首批获批的本土自主研发重组抗IL-17A人源化单克隆抗体，将打破同类进口药物的长期垄断局面，为银屑病患者提供新的治疗选择。除此之外，还有很多临床在研的靶向IL-17的生物制剂，包括荃信生物的QX-002N，康方生物的AK-111和君实生物的JS005等。 04 IL-6靶向制剂白介素-6（IL-6）是趋化因子家族的一种细胞因子，主要由单核巨噬细胞、 Th2细胞、血管内皮细胞、成纤维细胞产生。 IL-6的受体蛋白，由特异性的IL-6结合受体蛋白（IL-6R），和被称为信号转导蛋白的gp130所组成。按照信号传导方式的差异，IL-6参与的信号途径，可以分为经典信号通路（classical signaling）和转信号通路（Trans-signaling）。在经典信号通路中，IL-6与其膜结合受体mIL-6R、可溶性受体sIL-6R结合后，招募gp130（一种跨膜蛋白，细胞因子受体）结合形成IL-6-IL-6R-gp130六聚体，触发下游JAK-STAT、RAS-RAF等信号通路转导和基因表达。在转信号通路中，IL-6-sIL-6R复合物与gp130结合，启动细胞内信号转导，促进细胞增殖、分化、氧化应激和免疫调节（图7）[3]。图7. IL-6信号转导和IL-6受体系统的模式 IL-6信号通路异常与很多疾病的发病机制有关，包括类风湿性关节炎（RA）、系统性幼年特发性关节炎(sJIA)、Castleman病、巨细胞动脉炎（GCA）、大动脉炎和细胞因子释放综合征（CRS）等。目前全球有4款药物获批上市，包括靶向IL-6R的托珠单抗、Sarilumab、和萨特利珠单抗以及靶向IL-6的司妥昔单抗，其中托珠单抗由于上市时间早应用广泛，销售额遥遥领先，受益于用于新冠治疗的获批，曾在2021年达到销售峰值39.6亿美元。图8. 部分靶向IL-6的药物除此之外，临床上还有很多在研的IL-6或IL-6R拮抗剂药物，为了提高竞争性，很多药企进行差异化布局，开发新的适应症，包括优时比的olokizumab、诺和诺德的ziltivekimab和罗氏的RG6179等（图6）。 Olokizumab最初由优时比公司研发，是一款靶向IL-6的人源化单抗。后来在2013年转让给了俄罗斯药企R-Pharm，目前正在进行RA领域的上市申请。 Ziltivekimab最初是由Corvidia Therapeutics研发的IL-6单抗药物，后于2020年6月，诺和诺德以21亿美元收购Corvidia Therapeutics，接管了其主要候选药物ziltivekimab的开发工作。 Ziltivekimab旨在阻断IL-6通路来降低全身炎症，从而降低动脉粥样硬化性心血管疾病（ASCVD）和慢性肾脏病（CKD）患者的主要心血管不良事件风险，具有延长的半衰期，可以通过每月一次皮下注射给药。 RG6179是由罗氏研发的IgG2类IL-6单抗，可阻断经典和转信号传导，用于糖尿病性黄斑水肿、自身炎症性疾病、黄斑水肿和葡萄膜性黄斑水肿。小结自免是一个很大的疾病领域，有很多疾病靶点，目前全球自身免疫病药物市场中，TNF-α和IL-12/IL-23两个自免领域老靶点抑制剂销售额仍位居前列，而JAK、IL-4R、IL-17A、IL-6、IL-5、URAT1、TSLP、MASP-2、TYK2等靶点，则吸引较多创新药企布局，本文主要介绍JAK、IL-4R、IL-17A和IL-6四个热门自免靶点及其研发进展。参考文献 1.Aikaterini Tsiogka et.al, The JAK/STAT Pathway and Its Selective Inhibition in the Treatment of Atopic Dermatitis: A Systematic Review, J. Clin. Med. 2022, 11, 4431 2.Mandy J. McGeachy, Daniel J. Cua, and Sarah L. Gaffen, The IL-17 Family of Cytokines in Health and Disease, Immunity 50, April 16, 2019 3.Masashi Narazaki and Tadamitsu Kishimoto, The Two-Faced Cytokine IL-6 in Host Defense and Diseases, Int. J. Mol. Sci. 2018, 19, 3528. BiG近期会议 10月26日，第三届生物计算大会保留栏目-第二届吐槽大会即将再度来袭！将围绕投融资、行业心态、年轻人，及AI等热门话题展开策划，通过移幕换景，大咖带新秀，一同探讨AI+Biomed的融合之道！ ▼ 10月31日，BiG联合Citeline，将于10月底，举办自免小规模私董研讨会，聚焦：TCE vs. CAR-T，自身免疫开发策略，线上同步直播，敬请期待！ ▼ 共建Biomedical创新生态圈！如何加入BiG会员？

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药物(靶点)	适应症	全球最高研发状态

Olokizumab ( IL-6 )	类风湿关节炎更多	申请上市
Odelepran ( Opioid receptors )	酗酒更多	申请上市
咪达那新 ( M1 receptor x M3 receptor )	尿频更多	申请上市
Goflikicept ( IL-1β )	家族性地中海热更多	临床2期
ZD19-0144 ( MEK )	BRAF V600E阳性黑色素瘤更多	临床前