CYP3A4抑制剂(细胞色素P450家族成员3A4抑制剂)、CYP3A5抑制剂(cytochrome P450 family 3 subfamily A member 5 inhibitors)、CYP3A7抑制剂(cytochrome P450 family 3 subfamily A member 7 inhibitors)

治疗领域

免疫系统疾病感染泌尿生殖系统疾病

在研适应症

HIV感染

非在研适应症

获得性免疫缺陷综合征实体瘤

原研机构

Gilead Sciences, Inc.

在研机构

Gilead Sciences Ireland UC

Fore Biotherapeutics, Inc.Gilead Sciences Pty Ltd.

非在研机构

Gilead Sciences, Inc.

ViiV Healthcare Ltd.

权益机构-

最高研发阶段批准上市

首次获批日期

欧盟 (2013-09-19),

HIV感染

最高研发阶段(中国)-

特殊审评快速通道 (美国)、孤儿药 (美国)

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结构/序列

分子式C40H53N7O5S2

InChIKeyZCIGNRJZKPOIKD-CQXVEOKZSA-N

CAS号1004316-88-4

关联

项与考比司他相关的临床试验

NCT07462559

/ Not yet recruiting临床1期IIT

KF2025#1 Trial: Ketamine, Cannabidiol and Cobicistat Interaction Study

Ketamine is a dissociative anesthetic developed approximately 60 years ago. Both ketamine and its isomer, esketamine, have been used for over 20 years in the treatment of treatment-resistant depression. Other treatment options for this type of depression include combinations of antidepressants, other medications used in depression treatment (such as lithium), psychotherapy, electroconvulsive therapy, and repetitive transcranial magnetic stimulation. The advantage of ketamine and its stereoisomer, esketamine, over other treatment options is their rapidly emerging antidepressant effect, which becomes apparent within the first few days of treatment.
Ketamine is primarily metabolized by the cytochrome P450 (CYP) 3A4 enzyme, but also by the CYP2B6 and CYP2C9 enzymes. However, information on the significance of these different enzymes in ketamine metabolism is incomplete. Due to extensive first-pass metabolism, the bioavailability of orally administered ketamine varies significantly and is, on average, only 8-24%. This makes ketamine unsuitable for oral administration. In the treatment of depression, ketamine is administered as a slow intravenous infusion.
The concurrent use of medications that inhibit ketamine metabolism can significantly increase the bioavailability of orally administered ketamine. Cobicistat is a potent inhibitor of the CYP3A4 enzyme, which can significantly increase ketamine bioavailability and reduce interindividual variability by inhibiting ketamine's CYP3A4-mediated metabolism. This might enable the oral use of ketamine.
Cannabidiol is a cannabinoid that does not have addictive effects, but may have antidepressant and anxiolytic effects. Cannabidiol might reduce the dissociative side effects associated with ketamine treatment. Clinically, cannabidiol appears to moderately inhibit CYP enzymes in the order of potency: CYP2C19 > CYP2C9 > CYP3A > CYP1A2, and based on in vitro data, it also somewhat inhibits the CYP2B6 enzyme, which is involved in ketamine metabolism. However, its effect on ketamine concentrations cannot be assessed based on current knowledge.
The purpose of this study is to investigate the potential effects of cannabidiol, cobicistat, and their concurrent administration on the pharmacokinetics of orally administered ketamine. A secondary objective is to study the effect of cannabidiol on ketamine-induced side effects.
Study Methodology: This is a four-phase, randomized, open-label, crossover study involving 12 healthy volunteers. On study days, participants will receive a 56 mg oral dose of ketamine in the research facility, alternately with water, cannabidiol, cobicistat, or both cannabidiol and cobicistat. There will be at least a two-week washout period between study days.
The pharmacokinetics of ketamine and other study drugs will be investigated by taking blood samples according to a separate schedule for 11 hours after administration on the study day and the following morning. Pharmacokinetic parameters will be calculated from plasma concentrations of ketamine, cobicistat, cannabidiol, and their metabolites. The primary outcome measure is the total area under the curve (AUC0-∞) of ketamine. Additionally, the effects of the drugs on blood pressure, heart rate, and subjective adverse feeling of the study participants will be examined.

开始日期2026-03-04

申办/合作机构

Helsinki University Central Hospital

[+1]

NCT06726382

/ Completed临床1期IIT

KF2024#1-trial: Esketamine Interaction Study

Esketamine is a drug which is used for depression treatment, to relieve pain and, in larger doses, in anesthesia. Spravato nasal spray is the only esketamine product on the market used for the treatment of depression, but the high price limits the use of the drug.
The aim of this study is to compare the concentration of esketamine after nasal (licensed product Spravato) and oral administration with and without a CYP3A4 inhibitor. Grapefruit juice and cobicistat are studied as CYP3A4 inhibitors in the study.
In an open four-phase, randomized, alternating study with 12 healthy volunteers, the subjects will receive Spravato 28 mg nasal or esketamine 28 mg oral with either grapefruit juice, cobicistat or water in the study facilities. Blood samples will be collected and esketamine pharmacokinetics will be monitored up to 24 hours postdose. Primary endpoint is area under the plasma concentration-time curve of esketamine.

开始日期2024-12-09

申办/合作机构

Helsinki University Central Hospital

[+1]

NCT06337032

/ Recruiting临床4期

An Open-label, Single-arm Study to Provide Continued Access to Study Drug to Participants Who Have Completed Pediatric Clinical Studies Involving Gilead HIV Treatments

The goal of this clinical study is to provide continued access to the study drug(s) to children and adolescents with human immunodeficiency virus type 1 (HIV-1) who completed their participation in an applicable parent study and to monitor for adverse events.
The primary objectives of this study are as follows:
* To provide continued access to the study drug received in the parent protocol or switch to bictegravir/emtricitabine/tenofovir (B/F/TAF) for participants who completed a Gilead parent study evaluating drugs for HIV treatment.
* To evaluate the safety of the study drug(s) in participants with HIV-1.

开始日期2024-08-27

申办/合作机构

Gilead Sciences, Inc.

100 项与考比司他相关的临床结果

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100 项与考比司他相关的转化医学

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100 项与考比司他相关的专利（医药）

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978

项与考比司他相关的文献（医药）

2026-12-31·ANNALS OF MEDICINE

Efficacy and metabolic outcomes of switching from an INSTI-based triple-drug regimen to dolutegravir/lamivudine in treatment-experienced HIV-1-infected patients: a 48-week real-world study

Article

作者: Li, Qisui ; Zhang, Wei ; Yuan, Jing ; Deng, Changgang

BACKGROUND:

Real-world data on switching from INSTI-based triple therapy to DTG/3TC in the Chinese population are lacking.

METHODS:

This retrospective study included 214 treatment-experienced patients with HIV from Chongqing Public Health Medical Center (2021-2022) on an INSTI-based triple-drug regimen for ≥6 months who switched to DTG/3TC for >12 months. Patients with pre-existing metabolic diseases were excluded. Participants were categorized: INSTI+TAF-free (n = 100, prior TDF/AZT/ABC), INSTI+TAF (n = 56, prior BIC/FTC/TAF), and INSTI+TAF+COBI (n = 58, prior EVG/c/FTC/TAF). Virological, immunological, and metabolic parameters were assessed at weeks 24 and 48.

RESULTS:

The INSTI+TAF+COBI group was significantly older (p=0.000). Virological suppression rates (<50 copies/mL) were high at switch (93%, 85.7%, 91.4%). The INSTI+TAF+COBI group had lower eGFR and higher TG, TC, HDL, and LDL at baseline (p < 0.05). After switching, virological suppression remained high (≥90%) at weeks 24 and 48. CD4+ T-cell increases showed no significant intergroup differences. Metabolic changes differed: TC changes were 0.57 mmol/L (IQR: -0.19-0.91) in INSTI+TAF-free, -0.09 mmol/L (-0.47-0.71) in INSTI+TAF, and -0.25 mmol/L (-0.99-0.33) in INSTI+TAF+COBI. LDL changes were 0.23 mmol/L (-0.23-0.67), -0.15 mmol/L (-0.39-0.01), and -0.18 mmol/L (-0.71-0.10), respectively. TC and LDL changes differed significantly among groups (p < 0.05).

CONCLUSION:

Switching to DTG/3TC maintained virological suppression and stable immunological outcomes. Patients previously on TAF-containing regimens demonstrated greater metabolic benefits than those on TAF-free regimens, possibly related to baseline TDF effects, requiring further confirmation.

2026-08-01·JOURNAL OF INFECTION AND CHEMOTHERAPY

Results of three multicenter observational studies of regimens containing tenofovir alafenamide among people with HIV in Japan

Article

作者: Ohwaki, Ichiro ; Ohnishi, Makiko ; Lee, KuanYeh ; Serejo, Margarida ; Ishizaki, Akinobu ; Peters, Jami ; Taguchi, Nao

BACKGROUND:

Safety data on tenofovir alafenamide (TAF)-containing regimens with >2 years' follow-up in large cohorts of people with HIV (PWH) in Japan are limited. We evaluated the safety of TAF-containing regimens among PWH in Japan, including combinations with emtricitabine (F/TAF), elvitegravir/cobicistat/emtricitabine (E/C/F/TAF), and bictegravir/emtricitabine (B/F/TAF).

METHODS:

Data were collected from medical records for three separate single-arm studies from the HIV-Related Drugs multicenter observational joint cooperative surveillance. Data cut-off periods for each study were: F/TAF, January 2017-April 2025; E/C/F/TAF, July 2016-November 2024; and B/F/TAF, April 2019-February 2025. Each cohort was managed independently and analyzed descriptively as a separate observational cohort, without cross-cohort comparative analyses.

RESULTS:

Safety analyses for the studies included 1678 patients who received F/TAF, 659 who received E/C/F/TAF, and 1495 who received B/F/TAF; 22.2%-35.2% of patients were treatment-naïve across the three TAF-containing products. Median (quartile [Q]1, Q3) treatment duration was 5.12 (2.50, 6.89), 3.10 (2.38, 6.00), and 3.00 (1.28, 4.48) years. Adverse drug reactions (ADRs) occurred in 12.0%-18.6% of patients across studies. The most common ADRs by preferred term were: F/TAF, hypertension (23 [1.4%]) and hyperuricemia (22 [1.3%]); E/C/F/TAF, dyslipidemia (9 [1.4%]) and insomnia (6 [0.9%]); and B/F/TAF, weight increased (32 [2.1%]) and insomnia (18 [1.2%]). Most ADRs initially occurred within the first six months of treatment. The frequency of serious ADRs was <5%; 1.3%-2.9% discontinued treatment due to ADRs.

CONCLUSIONS:

The findings from these studies are consistent with the known safety profiles of the three TAF-containing products. No new safety issues emerged.

2026-07-08·CLINICAL INFECTIOUS DISEASES

Renal and Cardiovascular Complications Following Type 2 Diabetes Mellitus in People With and Without HIV: Data From the Cohort Study on Morbidity and HIV in Sweden (COSMOHS) Between 2010 and 2024

Article

作者: Månsson, Fredrik ; Nauclér, Pontus ; Hedberg, Pontus ; Nowak, Piotr ; Elvstam, Olof ; Nilsson, Josefin ; Sparén, Pär ; Brännström, Johanna ; Mellgren, Åsa ; Carlander, Christina ; Wagner, Philippe ; Killander Möller, Isabela ; Eliasson, Björn ; Bäckdahl, Tintin ; Gisslén, Magnus

Abstract:

Background:

Type 2 diabetes mellitus (T2DM) is common among people with HIV (PWH), although studies comparing T2DM-related complications in people with and without HIV (PWoH) remain limited. This was assessed using data from the Cohort Study on Morbidity and HIV in Sweden (COSMOHS).

Methods:

Nationwide study including Swedish residents born 1930–2006, diagnosed with T2DM between 2010 and 2019, followed until 31 December 2024, using 7 national registers including national HIV and diabetes registers. Follow-up began at T2DM diagnosis. Outcomes included renal events, cardiovascular events, and all-cause mortality. Cox proportional regression estimated hazard ratios (adjHRs) by HIV status, stratified by propensity score quintiles of age, sex, migrant status, comorbidities, and socioeconomics.

Results:

350 PWH and 311 668 PWoH were included, with similar median follow-up time (PWH, 7.8 years; PWoH, 8.8 years). PWH had higher renal risk than PWoH (major adverse kidney event: adjHR, 2.04; 95% CI, 1.57-2.65) but no significantly increased cardiovascular risk (major adverse cardiovascular event: adjHR, 1.18; 95% CI, .87–1.60) or all-cause mortality. Findings were consistent across sensitivity analyses, including competing-risk models for death and excluding PWH receiving tenofovir disoproxil fumarate at baseline. Accounting for the benign plasma/serum-creatinine increase associated with bictegravir, cobicistat, dolutegravir, and rilpivirine, the increased renal risk remained, although not statistically significant. The renal risk was most prominent in PWH with BMI ≥30 kg/m2.

Conclusions:

In this nationwide cohort, PWH with T2DM exhibited higher risk of renal complications than PWoH, indicating enhanced renal monitoring may be warranted. Further research should investigate underlying mechanisms, including antiretroviral therapy, to guide clinical management.

项与考比司他相关的新闻（医药）

2026-09-01

·BioSpace

FORE Biotherapeutics Announces Positive Outcome from First Planned Interim Efficacy Analysis from FORTE Basket Study Evaluating Plixorafenib Monotherapy in Advanced Solid Tumors with BRAF Fusions

Independent Data Monitoring Committee recommends study should proceed as planned Fore expects to report topline results from BRAF fusion basket of the FORTE study in the second half of 2027 If positive, Fore Bio believes the primary analysis from the BRAF fusion basket would potentially enable the submission of a New Drug Application (NDA) to the U.S. FDA under the Accelerated Approval pathway PHILADELPHIA--(BUSINESS WIRE)--FORE Biotherapeutics, a registration stage company dedicated to developing targeted therapies to treat patients with cancer, today announced that following the first of two pre-specified interim efficacy analyses for the FORTE basket study evaluating plixorafenib as a monotherapy in patients with advanced solid tumors with BRAF fusions, including recurrent or progressive primary central nervous system (CNS) tumors harboring BRAF fusions, the Independent Data Monitoring Committee (IDMC) has recommended that the study should continue as planned. ezstandalone.cmd.push(function () { ezstandalone.showAds(131); }); This first interim efficacy analysis for the BRAF fusion basket was conducted by the IDMC and was pre-specified to evaluate plixorafenib at a defined efficacy threshold after the first 25 participants treated in this basket of the FORTE study had sufficient data for response assessment, in addition to the IDMC’s ongoing oversight for safety. A second interim efficacy analysis is anticipated once sufficient data is available from 50 participants in this basket. The primary endpoint of overall response rate (ORR), supported by duration of response, in the FORTE BRAF fusions basket is being evaluated in approximately 75 patients. “The passing of this first protocol-specified interim analysis for the BRAF fusion basket, and the second successful interim analysis in the FORTE study, is an important milestone and supports that tumor regressions continue to be observed, along with long duration of treatment, in patients treated with plixorafenib,” said Stacie Peacock Shepherd, M.D., Ph.D., Chief Medical Officer of Fore. “BRAF fusions are estimated to occur in approximately 1% of all solid tumors, yet there are no approved treatments for the vast majority of these patients and their prognosis remains extremely poor. BRAF fusions commonly occur in brain tumors, including in children and young adults, especially in low grade gliomas or rare glioneuronal tumors. Given plixorafenib’s novel dimer and paradox breaker mechanism of action that prevents MAPK activation, which supports the clinical activity and favorable tolerability being reported across several BRAF alterations and populations, we believe plixorafenib has the potential to become the first approved treatment option for the approximately 33,000 patients 1 with BRAF fusions.” William Hinshaw, Chief Executive Officer of Fore, commented, “Plixorafenib is emerging as a potential first-in-class and best-in-class next-generation BRAF inhibitor with a simple, once daily, oral dosing regimen without the PK booster cobicistat. At Fore Bio, we initiated studies in three areas of very high unmet need where we believe plixorafenib’s unique mechanism has the potential to add important clinical innovation and benefit for patients while getting to market as rapidly as possible, including in BRAF V600E central nervous system (CNS) tumors, BRAF fusions and rare BRAF V600E solid tumors. Plixorafenib has demonstrated activity across a wide number of tumors with BRAF alterations and has now passed two rigorous interim analyses, one for BRAF V600E CNS tumors and one for tumors with BRAF fusions, both encouraging milestones for the FORTE program. As we look ahead to the remainder of 2026 and into next year, we expect to achieve several important milestones, including reporting topline results from the BRAF V600E CNS basket around the end of 2026, submitting an NDA for the treatment of BRAF V600E CNS tumors during the first half of 2027, and reporting topline results from the BRAF fusion basket during the second half of 2027.” Overview of Supporting Phase 1/2a BRAF Fusion Results 2 In a Phase 1/2a study in adults with advanced solid tumors harboring BRAF fusions (n=14), plixorafenib achieved a 14% ORR, including one complete response (CR) and one partial response and 7 (50%) with stable disease, for a disease control rate of 64%. Both responders continue treatment under sIND with a total duration of over 8 years for the patient with CR and over 4 years for the patient with PR. Overall, plixorafenib was well tolerated with Grade 3 or higher adverse events attributed to plixorafenib occurring in less than 10% of the 113 participants. Plixorafenib demonstrated a manageable dermatologic safety pro no related skin events leading to dose reduction, interruption, or treatment discontinuation. Discontinuation for adverse events related to plixorafenib was less than 2%. ezstandalone.cmd.push(function () { ezstandalone.showAds(132); }); About the Global Phase 2 FORTE Basket Study The registration-intended FORTE Master Protocol is a global Phase 2 clinical trial which includes four baskets evaluating plixorafenib in distinct patient populations. The three monotherapy indications currently under evaluation are recurrent or progressive BRAF V600E primary CNS tumors, solid tumors with BRAF fusions and rare BRAF V600 mutated solid tumors. Plixorafenib is administered orally once daily (QD) with food as a monotherapy (no longer in combination with cobicistat). As part of the Bayesian adaptive design of the trial, interim efficacy analyses are conducted in each basket. The company previously reported a positive outcome from the BRAF V600 CNS basket in the third quarter of 2025. For the BRAF fusion basket, an additional interim efficacy analysis is anticipated once sufficient data is available from 50 participants. For the third basket of FORTE evaluating plixorafenib in rare BRAF V600 solid tumors, an interim efficacy analysis will be conducted after sufficient scans from approximately 25 patients are evaluated by the IDMC. About Advanced Solid Tumors with BRAF Fusions Solid tumors with BRAF fusions represent a high unmet medical need and a large development opportunity for plixorafenib. BRAF fusions occur in approximately 1% of all solid tumors, up to 2% of melanomas, and up to 4% of all brain gliomas. Limited treatment options are available, with approved therapies presenting limitations in tolerability and safety when administered. About Plixorafenib Plixorafenib is a novel BRAF inhibitor, with a unique mechanism of action that functions both as a dimer and paradox breaker, and that has demonstrated a differentiated and compelling monotherapy pro clinical studies. Plixorafenib received Breakthrough Therapy Designation by the U.S. Food and Drug Administration in April 2026. In a previously conducted Phase 1/2 study in patients with MAPK inhibitor naïve BRAF V600 primary recurrent CNS tumors (n=9), plixorafenib monotherapy demonstrated an ORR of 67% and a clinical benefit rate of greater than 75%. In patients with V600 alterations who were MAPK inhibitor naïve, plixorafenib achieved a 42% response rate with prolonged duration of response (mDOR 17.8 months), with a clinical benefit rate of >70%. Plixorafenib also demonstrated a favorable safety and tolerability pro tumor types, including relative to existing standard of care treatments for various BRAF altered tumors, with a discontinuation rate due to drug-related adverse events of less than 2%. Fore believes plixorafenib has the potential to overcome the limitations and tolerability challenges of currently available BRAF inhibitors, including high rates of rash, hemorrhage and growth effects in younger patients, through its unique mechanism of action targeting both BRAF Class I and Class II alterations, while avoiding the limitations of the earlier generation BRAF inhibitors that led to rapid recurrence of disease and the need for combination with a MEK inhibitor. About FORE Biotherapeutics ezstandalone.cmd.push(function () { ezstandalone.showAds(133); }); Fore is a registration stage targeted oncology company dedicated to developing innovative treatments that provide better outcomes for patients with the hardest-to-treat cancers. The Company’s lead asset plixorafenib (FORE8394 or PLX-8394) is a V600 and non-V600 BRAF inhibitor rationally designed with a first-in-class mechanism to address treatment gaps from 1 st and 2 nd generation BRAF inhibitors. For more information, please visit or follow us on X and LinkedIn . References Reflects Fore Bio’s 2034 estimates across G7 markets. Results presented at ASCO 2023 Annual Meeting and SNO 2023 Annual Meeting Contacts Investors and Media: Argot Partners 212.600.1902 | ForeBio@argotpartners.com

2026-07-29

·药事纵横

2028专利悬崖倒计时：全球已上市&中国未上市品种，谁值得提前布局？

中国仿制药行业处于结构性调整期，一致性评价、集采常态化、资本周期调整叠加，立项难度显著加大。在此背景下，笔者从专利出发，结合注册、竞品及市场表现，进行梳理盘点2028年中国化合物到期的化药品种，企业若能在窗口期内完成申报并获批，可精准把握专利到期后的市场替代窗口，实现第一梯队上市销售。经梳理，全球已上市且中国尚未上市&中国分子专利到期是2028年的化药品种有12个，这12个品种涵盖抗HIV、抗肿瘤、抗感染、代谢病、心血管等领域；技术难度从单一口服制剂到四联复方不等。信息来源：各大国家注册局、专利局、魔方等，图表自制竞争格局盘点：哪些品种竞争蓝海聚焦全球市场，这12个品种均已在主流国家之一获批上市。查看中国市场，这12个品种在中国尚未获批上市。而目前可视的中国竞争厂家在1-3家之内。——意味着竞争格局相对宽松，但窗口期有限。信息来源：各大国家注册局、专利局、魔方等，图表自制市场表现梳理：哪些值得优先关注细化查看这12个品种，筛选出3个机会品种，近三年销售额上亿美元，分别是考比司他四复方、盐酸莫莫替尼及复方西达尿苷地西他滨。同时，考虑到新品种Gepotidacin于2025年全球首上市，潜在机会品种，建议重点关注其在中国市场的开发机会。考比司他四复方近三年全球销售额是17.5、17.4及16.3亿美元；盐酸莫莫替尼近三年全球销售额是0.2、3.0及5.3亿美元。复方西达尿苷地西他滨近三年全球销售额是0.9、3.0及1.6亿美元。信息来源：IMS-MIADS数据库：全球上市年份注册局；内容自行梳理，图表自制重点品种——考比司他四复方，成熟抗HIV大品种，百亿市场谁来分？简介：考比司他四复方（考比司他+达芦那韦+恩曲他滨+富马酸丙酚替诺福韦），由强生制药（Janssen）推出，用于治疗成人和体重≥40kg小儿患者的1型人类免疫缺陷病毒（HIV-1）感染。中国分子专利到期：2028/2/22专利到期，以最晚专利考比司他化合物专利到期计算。全球主要国家进展：2017年9月欧盟获批上市，2018年7月美国获批上市，2019年6月日本获批上市。全球市场表现：考比司他四复方近三年全球销售额是17.5、17.4及16.3亿美元，为成熟的抗HIV大品种数据来源：IQVIA-MIDAS数据库，图表自制重点品种——盐酸莫莫替尼，填补骨髓纤维化贫血空白的精准品种，放量迅猛简介：莫莫替尼（momelotinib）由Sierra Oncology研发，是一种JAK1、JAK2与ALK2/ACVR1抑制剂，用于治疗骨髓纤维化。其差异化优势在于——在抑制JAK通路的同时，通过抑制ALK2调节铁调素水平，改善贫血，填补了骨髓纤维化合并贫血患者无法使用常规JAK抑制剂的临床空白。中国分子专利到期：2028/2/22专利到期。全球主要国家进展：2023年9月美国获批上市，2024年1月欧盟获批上市，尚未进入日本及中国。全球市场表现：盐酸莫莫替尼近三年全球销售额是0.2、3.0及5.3亿美元。盐酸莫洛替尼上市首年即实现快速放量，近三年全球销售额稳步增长并突破亿美元门槛。该品种填补了骨髓纤维化患者合并贫血时无法使用JAK抑制剂的临床空白，市场定位精准，增长动能强劲。数据来源：IQVIA-MIDAS数据库，图表自制重点品种——复方西达尿苷地西他滨，口服剂型替代注射，剂型改良的典型机会简介：西达尿苷+地西他滨（口服片剂），为地西他滨的口服前体药物，用于骨髓增生异常综合征（MDS）等血液肿瘤。中国分子专利到期：2028年10月16日。全球进展：2020年7月美国获批上市，2023年9月欧盟获批上市。剂型及对应中国阶段：片剂，目前中国I/II临床进行中。全球市场表现：复方西达尿苷地西他滨近三年全球销售额是0.9、3.0及1.6亿美元。数据来源：IQVIA-MIDAS数据库，图表自制潜在品种——GepotidacinMesylate，2025年全球首上市的新品种，市场培育期与专利到期期高度重叠简介：Gepotidacin ，GSK公司研发，用于治疗由大肠杆菌、肺炎克雷伯菌等易感菌株引起的单纯性尿路感染（uUTI），适用人群体重≥40kg的成人及12岁以上青少年患者，是治疗uUTI的首个创新口服抗生素。中国分子专利到期：2028年4月16日。全球主要国家进展：2025年3月美国获批上市。剂型及对应中国阶段：片剂，批准临床阶段。全球市场表现：2025年3月全球首次获批上市，2028年中国专利到期，仿制药开发周期与市场培育期高度重叠。若能在2028年率先获批，可同步承接原研快速放量的市场红利，而非争夺成熟市场的存量份额。写在最后 2026年5月中国数据保护政策也新鲜出炉，对于仿制药企而言，不仅仅需要考虑专利，还需要考虑数据保护，同时还需要结合竞品把握考虑如何在窗口期内完成从技术攻关到注册申报的全链条准备。这既考验研发效率，也考验对专利到期及数据保护节奏的精准把握。谁能在专利悬崖来临之际率先获批，谁就能在集采时代拿到第一梯队的入场券。作者简介：药丸，中国药科大学硕士毕业，具有法律及药学教育背景，拥有法律资格证和专利代理师资格证，致力研究药学和专利，做一颗有价值的药丸。参考资源：注册信息：NMPA、FDA、EMA、PMDA等官网专利信息：中国专利局、欧专局销售数据：IQVIA-MIDAS全球药品数据行业报告：医药魔方等立即扫码加入药事纵横交流群

2026-07-07

·Business Wire

FORE Biotherapeutics Announces Closing of Upsized $67.4 Million Series D-2 Extension Financing and Highlights Recent Plixorafenib Achievements

PHILADELPHIA--(BUSINESS WIRE)--FORE Biotherapeutics, a registration stage company dedicated to developing targeted therapies to treat patients with cancer, today announced the closing of an upsized Series D-2 extension financing of $67.4 million, bringing the total Series D-2 amount raised to $110 million. The financing was co-led by SR One, Medicxi, and SymBiosis and supported by a syndicate of new investors, including TaiAx, LG Technology Ventures, Primer Ventures and Axil, and all existing investors, including OrbiMed Advisors, HBM Healthcare Investments, Wellington Management, Cormorant Capital, Novartis Venture Fund, Windham Life Science Partners, Samsung and 3B Capital. Proceeds from the financing will be used to support the ongoing late-stage development of plixorafenib, including delivering on the topline data from the recurrent or progressive BRAF V600E primary CNS tumor basket of the FORTE study around the end of 2026, a subsequent regulatory submission, and continued development in additional distinct monotherapy indications including rare BRAF V600 mutated solid tumors and advanced solid tumors with BRAF fusions. “We are pleased with the progress at Fore this year, which allowed us to expand our investor base with new, quality healthcare investors and are grateful for the continued support from all our existing investors, which reflects their confidence in the potential for plixorafenib to disrupt the BRAF market,” said William Hinshaw, Chief Executive Officer of Fore. “With target enrollment now complete in the primary CNS tumor basket, we look forward to reporting topline data from this basket around the end of 2026. With the recent Breakthrough Therapy Designation granted to plixorafenib, we continue to progress towards a planned regulatory submission in 2027 for BRAF V600E CNS tumors and bringing this novel mechanism and differentiated profile to patients who are in need of improved therapeutic options.” Plixorafenib Updates Fore Bio also announced several positive program updates for its ongoing FORTE study demonstrating continued timely execution as well as notable patient-friendly improvements to the protocol: Target enrollment of approximately 50 patients has been reached in the BRAF V600E CNS tumor basket of the FORTE study, and topline data from the study is now anticipated around the end of 2026. This basket previously met the pre-specified interim analysis, with the Independent Data Monitoring Committee (IDMC) supporting that the study may continue as planned based on responses assessed by blinded independent central review (BICR), in addition to the IDMC’s ongoing oversight for safety. The company anticipates that the primary analysis of data from this basket, if positive, would enable the submission of a New Drug Application to the U.S. Food and Drug Administration under the Accelerated Approval pathway. Based upon the protocol-specified decision rule and available safety and PK data, clearance from the IDMC has been received to enroll patients as young as 8 years of age, compared to a prior age range starting at 10 years old, to align more closely with the observed BRAF-altered patient population including children and young adults in which low-grade gliomas (LGG) and other primary CNS tumors more commonly occur. Fore Bio has implemented an improvement to the dosing regimen in the FORTE study to administer plixorafenib with food, on the basis of a recent food effect study. On the basis of this data, and the supportive data from clinical studies showing robust exposures and anti-tumor activity with plixorafenib alone, cobicistat, an approved CYP3A inhibitor designed to serve as a PK booster, will no longer be administered with plixorafenib. Mr. Hinshaw concluded, “With several key clinical and regulatory catalysts on the horizon, we believe plixorafenib has the potential to meaningfully improve upon the current treatment paradigm, representing a significant opportunity across several BRAF-altered CNS tumor types including high and low grade glial and glioneuronal brain and spinal cord tumors, glioblastomas, and others, in addition to the distinct patient populations currently being evaluated in the FORTE study.” The company is currently evaluating plixorafenib in two additional monotherapy baskets in the FORTE study, in rare BRAF V600 mutated solid tumors and advanced solid tumors with BRAF fusions, respectively. The company anticipates advancing through multiple clinical and regulatory milestones across the plixorafenib development program throughout 2026 and into 2027. About the Global Phase 2 FORTE Basket Study The registration-intended FORTE Master Protocol is a global Phase 2 clinical trial which includes four sub-protocol baskets evaluating plixorafenib in distinct patient populations. The three monotherapy indications currently under evaluation are recurrent or progressive BRAF V600E primary CNS tumors, solid tumors with BRAF fusions and rare BRAF V600 mutated solid tumors. As part of the Bayesian adaptive design of the trial, interim efficacy analyses are conducted in each basket, for which the company reported a positive outcome from the BRAF V600 CNS basket in the third quarter of 2025. About Plixorafenib Plixorafenib is a novel BRAF inhibitor, with a unique mechanism of action that functions both as a dimer and paradox breaker, and that has demonstrated a differentiated and compelling monotherapy profile in clinical studies. Plixorafenib received Breakthrough Therapy Designation by the U.S. Food and Drug Administration in April 2026. In a previously conducted Phase 1/2 study in patients with MAPK inhibitor naïve BRAF V600 primary recurrent CNS tumors (n=9), plixorafenib monotherapy demonstrated an ORR of 67% and a clinical benefit rate of greater than 75%. In patients with V600 alterations who were MAPK inhibitor naïve, plixorafenib achieved a 42% response rate with prolonged duration of response (mDOR 17.8 months), with a clinical benefit rate of >70%. Plixorafenib also demonstrated a favorable safety and tolerability profile across tumor types, including relative to existing standard of care treatments for various BRAF altered tumors, with a discontinuation rate due to drug-related adverse events of less than 2%. Fore believes plixorafenib has the potential to overcome the limitations of currently available BRAF inhibitors through its unique mechanism of action targeting BRAF, while avoiding the limitations of the earlier generation BRAF inhibitors that led to rapid recurrence of disease and the need for combination with a MEK inhibitor. About FORE Biotherapeutics Fore is a registration stage targeted oncology company dedicated to developing innovative treatments that provide better outcomes for patients with the hardest-to-treat cancers. The Company’s lead asset plixorafenib (FORE8394; formerly PLX8394) is a V600 and non-V600 BRAF inhibitor rationally designed with a first-in-class mechanism to address treatment gaps from 1st and 2nd generation BRAF inhibitors. For more information, please visit www.fore.bio or follow us on X and LinkedIn.

临床2期临床结果临床1期突破性疗法

100 项与考比司他相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D09881	考比司他	V03AX03	DB09065

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
HIV感染	欧盟	Gilead Sciences Ireland UC	2013-09-19
HIV感染	冰岛	Gilead Sciences Ireland UC	2013-09-19
HIV感染	列支敦士登	Gilead Sciences Ireland UC	2013-09-19
HIV感染	挪威	Gilead Sciences Ireland UC	2013-09-19

未上市

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
获得性免疫缺陷综合征	临床3期	美国	Gilead Sciences, Inc.	2011-05-01
获得性免疫缺陷综合征	临床3期	澳大利亚	Gilead Sciences, Inc.	2011-05-01
获得性免疫缺陷综合征	临床3期	奥地利	Gilead Sciences, Inc.	2011-05-01
获得性免疫缺陷综合征	临床3期	加拿大	Gilead Sciences, Inc.	2011-05-01
获得性免疫缺陷综合征	临床3期	多米尼加共和国	Gilead Sciences, Inc.	2011-05-01
获得性免疫缺陷综合征	临床3期	德国	Gilead Sciences, Inc.	2011-05-01
获得性免疫缺陷综合征	临床3期	墨西哥	Gilead Sciences, Inc.	2011-05-01
获得性免疫缺陷综合征	临床3期	英国	Gilead Sciences, Inc.	2011-05-01
实体瘤	临床2期	美国	Fore Biotherapeutics, Inc.	2015-04-01

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临床结果

适应症

分期

评价

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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


NCT06014489 (HOVON 171, Pubmed \| Blood Neoplasia)	临床2期	急性髓性白血病	13	Azacitidine+Venetoclax	鑰衊膚餘糧製觸觸夢鹽(廠蓋鹽糧窪願鏇顧範襯) = 2.0 (90% CI, 1.4-2.8) 齋夢獵醖艱範壓繭簾網 (範餘願鬱築繭顧鹹鏇餘 ) 更多	积极	2026-05-01
NCT05494866 (IntenSify, AACR2026)	临床1期	胰腺癌 CYP3A5 expression	6	nab-paclitaxel+gemcitabine+cobicistat (Metastatic Pancreatic Cancer)	齋醖夢淵窪繭鬱衊鏇衊(鹽膚獵齋製顧願簾蓋壓) = One patient was hospitalized after 6 weeks of treatment for grade 4 acute respiratory distress syndrome associated with LDH increase and lung ground-glass opacity in the CT scan. Two more asymptomatic cases of ground glass opacity associated with LDH increase were observed. 膚積醖鑰鬱積蓋積艱憲 (鹹築網鹽壓餘餘蓋顧鑰 )	不佳	2026-04-21
NCT05458102 (Pubmed \| Infect Dis Ther)	临床1期	HIV感染	15	VesatolimodCobicistatd + VesatolimodCobicistat	鹹襯築鹽廠膚簾築遞網(願壓鬱簾艱壓鏇窪鹹觸) = 簾鬱獵蓋壓鹽積鏇鑰鬱選壓壓網壓鹽壓觸餘襯 (蓋顧鹹觸獵廠觸鹹壓獵 ) 更多	积极	2025-11-01
NCT03864406 (CTgov)	临床1期	-	12	rivaroxaban+cobicistat+Darunavir/Cobicistat	鹽壓鑰築艱願糧衊網簾(淵淵夢憲鏇廠鑰製鹹願) = 襯築蓋襯製壓獵廠餘齋鏇壓簾積構鏇糧觸壓網 (鹹願艱衊壓鹽醖製襯選, 401.58) 更多	-	2023-12-01
NCT04069221 (CTgov)	临床1期	疟疾	26	OZ439 (Part 2, Treatment B: Single Oral Dose of 800 mg OZ439)	齋繭觸齋顧襯鬱淵簾鹹(膚繭廠齋遞膚繭廠構選) = 獵壓遞鏇壓齋淵願夢鏇鑰網壓獵鑰願製壓襯選 (遞窪壓糧齋窪獵醖襯製, 36.1) 更多	-	2019-11-26
				OZ439 (Part 2, Treatment C: Single Oral Dose of 400 mg OZ439)	齋繭觸齋顧襯鬱淵簾鹹(膚繭廠齋遞膚繭廠構選) = 範顧鹹憲廠鬱夢選膚觸鑰網壓獵鑰願製壓襯選 (遞窪壓糧齋窪獵醖襯製, 40.7) 更多
NCT01815736 (Pubmed \| HIV Res Clin Pract)	临床3期	HIV感染	1,443	Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF)	鑰鬱遞鏇網壓積窪遞襯(網淵顧鏇簾蓋窪網齋襯) = There were no discontinuations due to renal AE, no cases of PRT or Fanconi syndrome in any of the studies 壓願築網網範窪鑰觸鏇 (鹽獵觸艱築糧顧衊糧範 )	-	2019-07-08
Pubmed \| J Acquir Immune Defic Syndr	临床3期	HIV感染	1,733	Tenofovir Alafenamide (TAF)	獵鏇壓構淵衊艱築憲鑰(鏇繭簾窪鏇構網構遞積) = TAF had less impact than TDF on bone mineral density 膚顧廠餘選遞窪顧蓋製 (製鑰觸鬱構遞窪糧窪鹹 ) 更多	积极	2017-06-01
				Tenofovir Disoproxil Fumarate (TDF)
IAS2017	N/A	HIV感染	33	Elvitegravir	膚艱壓膚齋艱餘鬱憲淵(願觸積鬱遞範獵範觸獵) = 鑰製構築範鑰積淵選壓淵範繭膚糧簾淵廠構衊 (築遞醖淵糧鬱蓋獵齋蓋 ) 更多	-	2017-01-01
				Cobicistat	膚艱壓膚齋艱餘鬱憲淵(願觸積鬱遞範獵範觸獵) = 遞願艱艱範襯齋獵鏇觸淵範繭膚糧簾淵廠構衊 (築遞醖淵糧鬱蓋獵齋蓋 ) 更多
NCT01815736 (Pubmed \| Lancet Infect Dis) 人工标引	临床3期	HIV感染	1,436	tenofovir alafenamide group	鬱顧鹹壓鹽壓窪製憲製(齋網壓膚夢膚築廠齋範) = 鏇壓顧襯繭壓齋壓衊廠餘遞餘鬱醖壓糧顧鬱範 (鏇選鬱網壓膚淵膚觸範 ) 更多	非劣	2016-01-01
				one of four previous tenofovir disoproxil fumarate-containing regimens	鬱顧鹹壓鹽壓窪製憲製(齋網壓膚夢膚築廠齋範) = 憲鏇願齋觸製鏇憲淵艱餘遞餘鬱醖壓糧顧鬱範 (鏇選鬱網壓膚淵膚觸範 ) 更多
Pubmed \| J Acquir Immune Defic Syndr	临床3期	-	698	Cobicistat	夢壓鹹夢網鏇餘廠簾窪(齋淵簾鹽鹹襯選蓋窪積) = 鬱顧顧憲顧鑰淵窪鬱觸餘艱觸窪遞遞網窪齋簾 (鑰構觸鑰鬱蓋廠齋積選 ) 更多	-	2015-07-01
				Ritonavir	夢壓鹹夢網鏇餘廠簾窪(齋淵簾鹽鹹襯選蓋窪積) = 網餘範鑰網淵鬱鏇鹹築餘艱觸窪遞遞網窪齋簾 (鑰構觸鑰鬱蓋廠齋積選 ) 更多