Our study rationale is based on:
1. Tuberculosis Preventive Treatment (TPT) is given to healthy people and needs to be safe;
2. Tuberculosis Preventive Treatment (TPT) with shorter regimens are superior with respect to acceptance, completion, and costs;
3. 4 months of Rifampin 10mg/kg (4R10) is the safest regimen, but is completed by <80% of patients;
4. The safety of 2 months of Rifampin 20mg/kg (2R20) is similar to that of 4 months of Rifampin 10mg/kg (4R10), but completion is a concern;
5. 1-month regimens have promising efficacy;
6. Safety and tolerability must be carefully assessed with comparisons to 4 months of Rifampin 10mg/kg (4R10), and head-to-head with each other.
OBJECTIVES: The investigator will use a Bayesian adaptive Phase 2 randomized open-label trial design to test at least three experimental Tuberculosis Preventive Treatment (TPT) regimens to identify at least one regimen of ≤2 months duration that has non-inferior safety, completion, and tolerability in adults and children relative to the reference Tuberculosis Preventive Treatment (TPT) regimen. The shortest, safest, and best tolerated regimen identified in this Phase 2 trial will be tested for effectiveness and efficacy in a Phase 3 trial.
Specific Tuberculosis Preventive Treatment (TPT) regimens (All are daily and self-administered) Reference: Rifampin at a dose of 10 mg/kg/day for 4 months (4R10); Experimental: 1) Rifampin at 20 mg/kg/day for 2 months (2R20); (2) one month Levofloxacin and Rifapentine (1LP). At a later stage a 3rd experimental regimen will be selected and added: one another novel 1-2-month regimen identified from pre-clinical and clinical studies. When selected, this will be explained fully including preliminary data on safety and efficacy in an amended protocol and consent - which will be submitted for ethics and regulatory approval at that time).

开始日期2025-02-01

申办/合作机构

Mcgill University Health Centre

[+1]

NCT06192160 / Not yet recruiting临床2期IIT

A Phase 2 Randomized, Adaptive, Dose-Ranging, Open-Label Trial of Novel Regimens for the Treatment of Pulmonary Tuberculosis

A5409/RAD-TB is an adaptive Phase 2 randomized, controlled, open-label, dose-ranging, platform protocol to evaluate the safety and efficacy of multidrug regimens for the treatment of adults with drug-susceptible pulmonary tuberculosis (TB).
A5409 hypothesizes that novel regimens for the treatment of pulmonary tuberculosis will result in superior early efficacy, as determined by longitudinal mycobacteria growth indicator tube (MGIT) liquid culture time to positivity (TTP) measurements over the first 6 weeks of treatment, and will have acceptable safety and tolerability over 8 weeks of treatment relative to standard of care [(SOC) isoniazid/rifampicin/pyrazinamide/ethambutol (HRZE)].
The study will run for 52 weeks, inclusive of 26 weeks of TB treatment comprised of 8 weeks of experimental or SOC treatment (based on treatment arm assignment) followed by 18 weeks of SOC treatment with 45 participants in each experimental treatment arm and at least 90 participants in the SOC arm.

开始日期2025-01-10

申办/合作机构

National Institute of Allergy & Infectious Diseases

[+1]

NCT06701136 / Not yet recruiting临床1期

A Clinical Study to Evaluate the Drug-Drug Interaction and Food Effect of Sudapyridine(WX-081) Tablet With Itraconazole and Rifampin in Healthy Chinese Adult Volunteers

The goal of this clinical trial is to learn how Sudapyridine (WX-081) tablets interact with other drugs and how food intake affects its pharmacokinetics in healthy Chinese adults. The main questions it aims to answer are:
How does itraconazole (a strong CYP3A inhibitor) affect the pharmacokinetics of Sudapyridine? How does rifampin (a strong CYP3A inducer) affect the pharmacokinetics of Sudapyridine? How does food intake influence the pharmacokinetics of Sudapyridine?
Participants will:
Take Sudapyridine alone, with itraconazole, with rifampin, and under fed and fasting conditions based on a predefined sequence.
Attend multiple clinic visits for blood sample collection and safety evaluations.
Researchers will compare the pharmacokinetic parameters of Sudapyridine under these conditions to determine the impact of drug-drug interactions and food.

开始日期2024-12-12

申办/合作机构

上海嘉坦医药科技有限公司

100 项与利福平相关的临床结果

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100 项与利福平相关的转化医学

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100 项与利福平相关的专利（医药）

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27,449

项与利福平相关的文献（医药）

2025-02-01·INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY

Transfer of Salmonella enterica and Enterococcus faecium from food-contact surfaces to stone fruits

Article

作者: Long, Xiaonuo ; Nitin, Nitin ; Harris, Linda J ; Xie, Yucen

Contaminated food-contact surfaces are a potential route for spreading microorganisms to stone fruit during postharvest handling. The objective of this study was to investigate the factors that affect the transfer of bacteria from food-contact surfaces to stone fruits. Coupons (1 × 1 cm) of polyurethane (PU) or polyvinyl chloride (PVC) were inoculated with rifampin-resistant variants of Salmonella (five-strain cocktail) or Enterococcus faecium NRRL B-2354 at ~5 or ~7 log CFU/cm². Inoculated coupons (n = 8-11) were attached to a texture analyzer, and uniform contact conditions (5 N, 5 s) were used to explore the impact of bacterial species, inoculation level, donor surface, the presence of dried peach juice or wax, recipient produce commodity, and the dryness of inoculum. Whole fruits were transferred to 20 mL of 0.1 % peptone, rubbed for 2 min, and then the diluent was plated onto tryptic soy agar supplemented with rifampin at 50 μg/mL. Whole fruits were enriched when populations were anticipated to fall below the limit of detection (1.6 log CFU/fruit). At an inoculum of ~5 log CFU/coupon, Salmonella and E. faecium were recovered from the fruit by enrichment but not by plating. At ~7 log CFU/coupon, transfer rates, i.e., ratio of populations on recipient fruit to donor surface, were not significantly (P > 0.05) influenced by either bacterial species (Salmonella [0.26 % ± 0.77 %] versus E. faecium [0.068 % ± 0.071 %]) or donor surface (PU [0.085 % ± 0.098 %] versus PVC [0.16 % ± 0.16 %]). The rates of transfer of E. faecium from contaminated PU to peaches (0.050 % ± 0.031 %), nectarines (0.066 % ± 0.076 %), and onion skins (0.048 % ± 0.059 %) were not significantly different. The mean transfer rates of E. faecium increased significantly (P < 0.05) in the presence of dried wax (18 % ± 16 %) or peach juice (1.3 % ± 2.6 %) on the PU surface compared with the control (0.080 % ± 0.086 %). The transfer rates of E. faecium from contaminated surfaces were also significantly influenced by the drying time post-inoculation; the drier the inoculum, the lower the transfer rates. The presence of residues or moisture on food-contact surfaces facilitated the transfer of microorganisms during dry handling of fresh stone fruits. The results underscore the importance of implementing adequate cleaning, sanitation and, where appropriate, drying of equipment surfaces to effectively remove organic residues and mitigate the risks of cross-contamination.

2025-02-01·BIORESOURCE TECHNOLOGY

Effects of antibiotic supplementation vs. nutrient stress on α-linolenic acid and α-tocopherol in Scenedesmus sp.

Article

作者: Ghosh, Tonmoy ; Bux, Faizal ; Bala, Kiran ; Ojha, Kanishka ; Chouhan, Vaibhav

The hormetic effects of antibiotics on Scenedesmus sp. werecompared with nitrogen limitationstrategies. We observed that 100 and 1000 nM supplementation with antibiotics could stimulate bothα-linolenic acid (ALA) and α-tocopherol productivities. Although nitrogen limitation had the best overall biomass and chlorophyll a productivity (∼ 43.83 % and 109.07 % ↑, respectively), tetracycline (1000 nM, T₁₀₀₀) was the best antibiotic for biomass (∼ 12.08 % ↑) while erythromycin (100 nM, E₁₀₀) was the best for chlorophyll a (∼ 52.19 % ↑). The antibiotics also triggered accumulation of monounsaturated fatty acids, like C16:1 and C18:1, which the nitrogen stress strategies failed to achieve. Rifampicin (100 nM, R₁₀₀) and E₁₀₀, with ∼3.92-4.14-fold increase in α-tocopherol and ∼4.41-4.81-fold increases in ALA productivities, reiterate the role of moderate stresses in stimulating high-value metabolites in microalgae. Our results provide an alternative medium engineering strategy for stimulating algal metabolites without compromising on the biomass. However, further studies are underwaytosafely remediate cultivation effluents and elucidate the physiological mechanisms of individual antibiotics to develop a more holistic strategy for targeted algal farming.

2025-02-01·Infectious disorders drug targets

Vigilance Needed in Treating a Child with Disseminated TB: A Case Report

Article

作者: Keshari Kar, Bikram ; Gaikwad, Nitin Rewaram ; Chouhan, Dushyant ; Velmurugan, Hemasri ; Thangaraju, Pugazhenthan ; Neelambaram, Krishnapriya ; Gurunthalingam, Meenalotchini Prakash

Background::

Tuberculosis is still one of the biggest causes of infection-related death around the world. Disseminated tuberculosis is a potentially fatal disease caused by the haematogenous spread of Mycobacterium tuberculosis. First-line anti-tuberculosis drugs in-clude isoniazid, rifampicin, pyrazinamide, and ethambutol. The first three drugs are known to cause hepatotoxicity.

Case Presentation::

We have, herein, reported a case of Drug-induced Liver Injury (DILI) due to anti-tuberculosis therapy in a one-year-old male child with disseminated tuberculosis. He was started on a fixed-dose combination of Anti-tuberculosis Therapy (ATT; isoniazid 50 mg, rifampicin 75 mg, and pyrazinamide 150 mg) and pyridoxine 10 mg orally. Initially, liver pa-rameters were normal, but later on with the course of the treatment, there was a rapid rise in liver enzymes, suggesting liver injury.

Discussion::

The association between liver injury and anti-tuberculosis therapy has been con-firmed by applying various causality association scales. It is obvious that proper treatment of disseminated tuberculosis can avoid the development of drug-resistant strains that can be harm-ful, worsening the prognosis as there are fewer therapeutic alternatives available. At the same time, there is a need to monitor the patient with ATT-induced DILI.

Conclusion::

The diagnosis of tuberculosis in children is difficult because of the mild, nonspe-cific clinical presentation, which usually reflects the implicated underlying organ. In addition to prompt diagnosis and treatment of disseminated TB, careful monitoring is equally important.

374

项与利福平相关的新闻（医药）

2024-12-13

·Business Wire

Gilead’s Seladelpar Receives Positive CHMP Opinion for Primary Biliary Cholangitis

FOSTER CITY, Calif.--( BUSINESS WIRE )--Gilead Sciences, Inc. (Nasdaq: GILD) today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion recommending seladelpar for the treatment of primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA) in adults who have an inadequate response to UDCA alone, or as monotherapy in those unable to tolerate UDCA. The final European Commission decision is anticipated in the first quarter of 2025. This follows the accelerated approval by the U.S. Food and Drug Administration (FDA) in August 2024. PBC is a rare, chronic, autoimmune disease of the bile ducts that affects approximately 15 per 100,000 people in Europe, primarily women, and can cause liver damage and possible liver failure if untreated. The most common symptoms of PBC are pruritus (chronic itch) and fatigue, which can be debilitating for some people. The disease currently has no cure and treatment goals for people living with PBC include suppressing liver damage and reducing the symptoms related to cholestasis. The effect of treatment on slowing disease progression is primarily measured by an improvement in liver biochemical tests, including the normalization of alkaline phosphatase (ALP) levels, an important marker of disease progression in PBC. “ This positive opinion from the Committee confirms promising clinical benefit and value of seladelpar, which has been underscored by its differentiated body of data,” said Palak Trivedi, MD, BSc (Hons), MBBS, MRCP (UK), ESEGH, PhD, Associate Professor and Consultant Hepatologist at the Queen Elizabeth Hospital in Birmingham. “ After many years of treating people with PBC, I have seen the critical unmet need for additional effective and symptom-directed treatment options. Today’s recommendation of a potential new therapy that can help treat both the disease and improve symptoms that impact quality of life is a significant milestone for the PBC community.” The positive opinion was supported primarily by data from the pivotal placebo-controlled Phase 3 RESPONSE study. In the study, 62% of participants taking seladelpar achieved the primary endpoint of composite biochemical response at month 12 compared with 20% of participants taking placebo. Treatment with seladelpar led to normalization of ALP values in 25% of trial participants at month 12. This change was not seen in any trial participants receiving placebo. ALP is a cholestatic marker that is a predictor of risk for liver transplant and death. Change from baseline pruritus score at month 6 was a key secondary endpoint; treatment with seladelpar led to a statistically significant reduction in pruritus compared with placebo. Participants entering the study with moderate to severe itch experienced a 3.2-point improvement on a pruritus scale of 0-10 after six months of treatment with seladelpar, compared to a decrease of 1.7 points with placebo. “ We are encouraged by the CHMP’s positive opinion as we are one step closer to providing seladelpar to people living with PBC in Europe,” said Timothy Watkins, MD, MSc, Vice President, Clinical Development of Inflammation Therapeutics, Gilead Sciences. “ There are still people living with PBC who do not have an adequate response to current medicines or who are still experiencing symptoms, such as debilitating itch. As a leader in liver disease, Gilead is committed to bringing forth therapies that not only improve markers of disease progression but also help alleviate symptoms which impact the lives of people living with this rare liver condition.” In addition to Europe, Gilead is working with regulatory authorities on marketing applications for seladelpar in other parts of the world. In August 2024, the FDA granted accelerated approval for seladelpar for the treatment of PBC in combination with (UDCA) in adults who have had an inadequate response to UDCA, or as monotherapy in patients unable to tolerate UDCA. Continued approval of seladelpar for the approved indication may be contingent on verification and description of clinical benefit in confirmatory trial(s). About RESPONSE (NCT04620733) RESPONSE is a Phase 3, double-blind, placebo-controlled clinical trial designed to evaluate the efficacy and safety of seladelpar in adults with PBC who have shown inadequate response or intolerance to first-line treatment with UDCA. The trial enrolled 193 participants across multiple sites worldwide. RESPONSE assessed key biomarkers of cholestasis, including ALP levels, as well as secondary endpoints related to liver function and patient quality of life. Participants in the RESPONSE trial received a daily oral dose of 10 mg of seladelpar or placebo for 12 months, with a focus on measuring changes in ALP and other relevant liver function tests. The trial aimed to address the high unmet need for effective second-line therapies for individuals with PBC, providing important insights into the long-term management of this chronic liver disease. About PBC PBC is a rare, chronic inflammatory liver disease primarily affecting women (1 in 1,000 women over the age of 40 or about 110,000 people in Europe). PBC is characterized by impaired bile flow (known as cholestasis) and the accumulation of toxic bile acids in the liver, leading to inflammation and destruction of the bile ducts within the liver and causing increased levels of ALP, alanine transaminase (ALT) and gamma-glutamyl transferase (GGT), enzymes found primarily in the liver, as well as total bilirubin. The most common symptoms of PBC are pruritus and fatigue, which can be debilitating for some people. Progression of PBC is associated with an increased risk of liver-related mortality. About Seladelpar Seladelpar is an oral PPAR-delta agonist, or delpar, for the treatment of PBC. PPAR-delta has been shown to regulate critical metabolic and liver disease pathways. Preclinical and clinical data indicate seladelpar has anticholestatic, anti-inflammatory, antipruritic, and antifibrotic effects. Seladelpar has potential to help meet the current unmet need of people living with PBC, as the first and only treatment that achieved statistically significant improvements across biochemical response, ALP normalization, and pruritus versus placebo. Pruritus is a common symptom that can significantly impair quality of life in people with PBC. Livdelzi ® (seladelpar) was granted accelerated approval for the treatment of PBC by the U.S. Food and Drug Administration (FDA) in August 2024. Seladelpar received FDA Breakthrough Therapy Designation, as well as Orphan Drug Designation for the treatment of people living with PBC. Seladelpar has Priority Medicine (PRIME) designation in the EU, which is assigned to optimize the development of novel medicines that target conditions with an unmet medical need for which no treatment options exists or where they can offer a major therapeutic advantage over existing treatments. Seladelpar is also under review by the UK Medicines and Healthcare products Regulatory Agency (MHRA). As part of the FDA accelerated approval, Gilead has committed to a confirmatory long-term outcomes study called AFFIRM, which has already been initiated in people with compensated cirrhosis. Continued U.S. approval may be contingent upon verification of clinical benefit in confirmatory trial(s). U.S. Indication for Livdelzi (seladelpar) 10mg capsules Livdelzi is indicated for the treatment of primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA) in adults who have had an inadequate response to UDCA, or as monotherapy in patients unable to tolerate UDCA. This indication is approved under accelerated approval based on a reduction of ALP. Improvement in survival or prevention of liver decompensation events have not been demonstrated. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s). Limitations of Use: Use of Livdelzi is not recommended in patients who have or develop decompensated cirrhosis (e.g., ascites, variceal bleeding, hepatic encephalopathy). U.S. Important Safety Information for Livdelzi Warnings and Precautions Fractures: Fractures occurred in 4% of LIVDELZI-treated patients compared to no placebo-treated patients. Consider the risk of fracture in the care of patients treated with LIVDELZI and monitor bone health according to current standards of care. Liver Test Abnormalities: LIVDELZI has been associated with dose-related increases in serum transaminase (AST and ALT) levels > 3 x ULN in patients receiving 50 mg and 200 mg once daily (5x and 20x higher than the recommended dosage of 10 mg once daily). Perform baseline clinical and laboratory testing when starting LIVDELZI and monitor thereafter according to routine patient management. Interrupt treatment if the liver tests (ALT, AST, total bilirubin, and/or ALP) worsen, or if the patient develops signs and symptoms of clinical hepatitis (eg, jaundice, right upper quadrant pain, eosinophilia). Consider permanent discontinuation if liver tests worsen after restarting LIVDELZI. Biliary Obstruction: Avoid use of LIVDELZI in patients with complete biliary obstruction. If biliary obstruction is suspected, interrupt LIVDELZI and treat as clinically indicated. Adverse Reactions The most common adverse reactions (≥5%) with LIVDELZI were headache (8%), abdominal pain (7%), nausea (6%), abdominal distension (6%), and dizziness (5%). Drug Interactions OAT3 Inhibitors and Strong CYP2C9 Inhibitors: Avoid coadministration with LIVDELZI due to increased LIVDELZI exposure. Rifampin: Monitor biochemical response (e.g., ALP and bilirubin) when patients initiate rifampin during LIVDELZI treatment. Coadministration may result in delayed or suboptimal biochemical response of LIVDELZI. Dual Moderate CYP2C9 and Moderate-to-Strong CYP3A4 Inhibitors and BCRP Inhibitors (e.g., cyclosporine): Monitor closely for adverse effects. Concomitant administration with LIVDELZI may increase LIVDELZI exposure. CYP2C9 Poor Metabolizers Using Moderate-to-Strong CYP3A4 Inhibitors: Monitor more frequently for adverse reactions as concomitant use of a moderate-to-strong CYP3A4 inhibitor in patients who are CYP2C9 poor metabolizers may increase LIVDELZI exposure and risk of LIVDELZI adverse reactions. Bile Acid Sequestrants: Administer LIVDELZI at least 4 hours before or 4 hours after taking a bile acid sequestrant, or at as great an interval as possible. Pregnancy and Lactation Pregnancy: There are insufficient data from human pregnancies exposed to LIVDELZI to allow an assessment of a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Report pregnancies to Gilead Sciences, Inc., at 1-800-445-3235. Lactation: There are no data on the presence of LIVDELZI in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for LIVDELZI and any potential adverse effects on the breastfed infant from LIVDELZI. About Gilead Sciences in Liver Disease For decades, Gilead has pioneered the way forward to improve the lives of people living with liver disease around the world. The company has helped to transform hepatitis C from a chronic condition into one that can be cured for millions of people. For individuals living with hepatitis B or D, Gilead's focus on advancing medicines drives hope that today’s research will turn into tomorrow’s cures. Beyond viral hepatitis, Gilead is working to deliver advanced treatments for people living with PBC. The commitment of Gilead doesn’t stop there. Through ground-breaking science and collaborative partnerships, the company strives to create healthier futures for everyone living with liver disease. Gilead remains devoted to a future without liver disease. About Gilead Sciences Gilead Sciences, Inc. is a biopharmaceutical company that has pursued and achieved breakthroughs in medicine for more than three decades, with the goal of creating a healthier world for all people. The company is committed to advancing innovative medicines to prevent and treat life-threatening diseases, including HIV, viral hepatitis, COVID-19, cancer and inflammation. Gilead operates in more than 35 countries worldwide, with headquarters in Foster City, California. Forward-Looking Statements This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including Gilead’s ability to initiate, progress or complete clinical trials within currently anticipated timelines or at all, and the possibility of unfavorable results from ongoing or additional clinical trials, including those involving Livdelzi (seladelpar) (such as the RESPONSE and any confirmatory studies); uncertainties relating to regulatory applications and related filing and approval timelines, including European Commission and MHRA reviews of seladelpar for the treatment of PBC; the risk that any regulatory approvals, if granted, may be subject to significant limitations on use or subject to withdrawal or other adverse actions by the applicable regulatory authority; and any assumptions underlying any of the foregoing. These and other risks, uncertainties and factors are described in detail in Gilead’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2024, as filed with the U.S. Securities and Exchange Commission. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. The reader is cautioned that any such forward-looking statements are not guarantees of future performance and involve risks and uncertainties and is cautioned not to place undue reliance on these forward-looking statements. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation and disclaims any intent to update any such forward-looking statements.

临床结果突破性疗法孤儿药临床3期加速审批

2024-12-13

·和黄医药官微

和黄医药宣布继FRUZAQLA® (呋喹替尼) 在欧洲首次纳入医保将获得来自武田的里程碑付款

中国香港、上海和美国新泽西州：2024年12月13日，星期五：和黄医药(中国)有限公司 (简称 "和黄医药" 或 "HUTCHMED") (纳斯达克/伦敦证交所: HCM; 香港交易所: 13) 今日宣布将收到一笔来自合作伙伴武田 (TSE: 4502/ NYSE: TAK) 的1千万美元的里程碑付款。武田于2024年12月在西班牙取得FRUZAQLA®用于治疗经治的转移性结直肠癌患者获纳入公共医疗保障范围的建议，这是在欧洲取得的首个纳入公共医疗保障范围的建议。结直肠癌是欧洲第二大癌症相关死亡原因。 — 继在欧洲首次纳入医保后，和黄医药将收到1千万美元的里程碑付款 — — FRUZAQLA® (呋喹替尼) 于2024年6月在欧盟获批，成为欧洲超过十年来首个获批用于治疗转移性结直肠癌的口服创新靶向疗法，无论患者的生物标志物状态如何 — FRUZAQLA®于2024年6月在欧盟取得欧盟委员会 ("EC") 批准。武田拥有在中国内地、香港和澳门以外进一步开发、商业化和生产呋喹替尼的全球独家许可。我们为合作伙伴武田以及西班牙的患者感到非常高兴，他们现在能够通过医保取得这种创新的疗法。这也是在欧洲更广泛地提高患者可及性所迈出的重要一步。这不仅见证了我们与武田的持续合作，也更彰显了我们致力解决转移性结直肠癌患者需求的共同承诺。和黄医药首席执行官兼首席科学官苏慰国欧盟委员会的批准主要是基于FRESCO-2国际多中心III期研究的结果。FRESCO-2 研究的数据已在2023 年 6 月发表于《柳叶刀 (The Lancet)》。呋喹替尼于2023年11月在美国、2024年6月在欧盟、2024年8月在瑞士、2024年9月在加拿大、日本和英国，以及于2024年10月在阿根廷、澳洲和新加坡获批。在其他多个国家和地区的监管申请亦在进行中。关于结直肠癌结直肠癌是始于结肠或直肠的癌症。根据国际癌症研究机构 (IARC)/世界卫生组织 (WHO) 的数据，结直肠癌是全球第三大常见癌症，在2022年估计有超过190万例新增病例，并造成超过90万人死亡。在欧洲，结直肠癌是第二大常见癌症，2022年约有53.8万例新增病例和24.8万例死亡。[1],[2] 在美国，2024年估计将新增15.3万例结直肠癌新症以及5.3万例死亡。[3] 在日本，结直肠癌是最常见的癌症，2022年估计有14.6万例新增病例和6万例死亡。[2] 尽管早期结直肠癌能够通过手术切除，但转移性结直肠癌目前治疗结果不佳且治疗方案有限，仍然存在大量未被满足的医疗需求。虽然部分转移性结直肠癌患者或可受益于基于分子特征的个性化治疗策略，然而大部分患者未携带可作为治疗靶点的突变。[4-8] 关于呋喹替尼呋喹替尼是一种选择性针对所有三种VEGFR (VEGFR-1、-2及-3) 的口服抑制剂。VEGFR抑制剂在抑制肿瘤的血管生成中起到至关重要的作用。呋喹替尼被设计为拥有更高的激酶选择性，旨在降低脱靶激酶活性，从而实现对靶点持续覆盖的药物暴露以及当潜在作为联合疗法时拥有更高的灵活度。关于呋喹替尼获批向全球监管机构提交的注册申请是基于两项大型、随机对照III期临床试验的数据，即国际多中心临床试验FRESCO-2研究以及于中国开展的FRESCO研究，在总共734名接受呋喹替尼治疗的患者中展现出了一致的获益。各项研究的安全性特征亦保持一致。FRESCO-2研究的结果已在2023年6月于《柳叶刀 (The Lancet)》发表，[9] FRESCO研究的结果则已于《美国医学会杂志 (JAMA)》上发表。[10] 在中国内地、香港和澳门，呋喹替尼由和黄医药及礼来公司合作以商品名爱优特® (ELUNATE®) 上市销售。其于2020年1月获纳入中国国家医保药品目录。自呋喹替尼在中国上市以来已有超过10万名结直肠癌患者接受呋喹替尼治疗。欧洲重要安全性信息处方前请参阅 FRUZAQLA (呋喹替尼) 产品特性摘要 (SmPC)。使用指南：FRUZAQLA 应该由具有抗肿瘤治疗经验的医生起始使用。应向患者提供包装说明书。禁忌：对活性成分或任何赋形剂过敏。特殊人群：肾功能不全：轻度、中度或重度肾功能不全患者无需调整剂量；肝功能不全：轻度或中度肝功能不全患者无需调整剂量。重度肝功能不全的患者不建议使用 FRUZAQLA，因为尚无FRUZAQLA针对该人群的研究；老年人：65岁以上患者无需调整剂量；儿童人群：FRUZAQLA 在儿童人群中没有用于转移性结直肠癌适应症的相关使用数据；育龄妇女/女性避孕：应建议育龄妇女在治疗期间以及最后一次服用 FRUZAQLA 后至少 2 周内使用高效避孕措施；妊娠：尚无FRUZAQLA用于孕妇的临床数据。根据其作用机制，FRUZAQLA 有可能对胎儿造成伤害。动物研究显示生殖毒性，包括胎儿畸形。FRUZAQLA 不应在怀孕期间使用，除非妇女的临床情况需要 FRUZAQLA 治疗。如果在怀孕期间使用 FRUZAQLA 或患者在治疗期间怀孕，必须告知患者对胎儿的潜在危害；哺乳：尚未确定哺乳期间是否可以安全使用FRUZAQLA。目前尚不明确FRUZAQLA 或其代谢物是否会经人乳排泄。没有关于 FRUZAQLA 经动物乳汁排泄的动物数据。不能排除母乳喂养的新生儿/婴儿所面临的风险。治疗期间及最后一次服药后 2 周内应停止哺乳；生育力：尚无关于 FRUZAQLA影响人类生育力的数据。动物研究结果显示 FRUZAQLA 可能会损害雄性和雌性生育力。警告及注意事项 ·高血压：接受FRUZAQLA 治疗的患者中曾报告出现高血压，包括高血压危象。在开始FRUZAQLA治疗之前，应根据标准医疗实践监测并充分控制已存在的高血压。高血压应使用抗高血压药物进行药物治疗，并在必要时调整 FRUZAQLA 的剂量。对于无法通过降压治疗控制的高血压或出现高血压危象的患者，应永久停用 FRUZAQLA。 ·出血事件：接受FRUZAQLA 治疗的患者中曾报告出现出血事件，包括胃肠道出血。接受FRUZAQLA 治疗的患者中曾报告出现严重或甚至危及生命的出血事件。对有出血风险的患者 (包括接受抗凝血剂或其他会增加出血风险的合并药物治疗的患者) 应根据标准医疗实践进行血液学和凝血特征监测。若发生需要立即进行医疗干预的严重出血，应永久停用 FRUZAQLA。 ·胃肠穿孔：接受FRUZAQLA 治疗的患者中曾报告出现胃肠穿孔事件，包括致命事件。FRUZAQLA 治疗期间应定期监测胃肠穿孔症状。发生胃肠穿孔的患者应永久停用 FRUZAQLA。 ·蛋白尿：接受FRUZAQLA 治疗的患者中曾报告出现蛋白尿。在开始使用FRUZAQLA之前和整个治疗过程中应根据标准医疗实践监测蛋白尿。若尿液试纸检测到24小时蛋白尿≥2g，可能需要中断剂量、调整剂量或停药。出现肾病综合征的患者应永久停用 FRUZAQLA。 ·掌跖红肿感觉综合征 (PPES) ：掌跖红肿感觉综合征是最常报告的皮肤不良反应。如果监测到≥2级以上皮肤反应，可能需要中断剂量、调整剂量或停药。 ·可逆性后部脑病变综合征 (PRES) ：在临床研究中，曾报告一例 (0.1%) 接受FRUZAQLA 治疗的患者出现可逆性后部脑病变综合征。这是一种罕见的神经系统疾病，可表现为头痛、癫痫发作、嗜睡、精神错乱或精神功能改变、失明及其他视觉或神经系统障碍，伴随或不伴随高血压。可逆性后部脑病变综合征需要通过脑部影像学检查确诊，最好是磁共振成像 (MRI)。对于出现可逆性后部脑病变综合征的患者，建议停用 FRUZAQLA，并同时给予控制高血压和其他症状的支持性医疗管理。 ·伤口愈合延迟：在临床研究中，曾报告一例 (0.1%) 接受FRUZAQLA 治疗的患者出现伤口愈合延迟。建议患者在大手术前至少2周不要服用 FRUZAQLA。大手术后至少2周内请勿使用FRUZAQLA，直到根据临床指征有证据显示伤口充分愈合。 ·动脉和静脉血栓栓塞事件：建议在过去6个月内有血栓栓塞事件史 (包括深部静脉血栓形成和肺栓塞) 或在过去12个月内有中风和/或短暂性脑缺血发作病史的患者，建议避免开始 FRUZAQLA治疗。对于怀疑出现动脉血栓栓塞的患者，应立即停用FRUZAQLA。药物相互作用其他药品对 FRUZAQLA 的药代动力学影响 CYP3A诱导剂 FRUZAQLA合与利福平 (rifampicin，一种强效 CYP3A 诱导剂) 600 mg 每日一次联合给药，使FRUZAQLA的 AUCinf降低 65%，Cmax 降低 12%。应避免 FRUZAQLA 与强效和中度 CYP3A 诱导剂同时给药。 CYP3A抑制剂 FRUZAQLA与伊曲康唑 (itraconazole，一种强效 CYP3A 抑制剂) 200 mg 每日两次联合给药，未对血浆药物浓度-时间曲线下面积 (AUC) 和Cmax产生临床显著性影响。与 CYP3A 抑制剂联合给药时无需调整 FRUZAQLA 的剂量。抑酸药物 FRUZAQLA与雷贝拉唑 (rabeprazole，一种质子泵抑制剂) 40 mg 每日一次联合给药，未对FRUZAQLA的AUC产生临床显著性影响。与抑酸药物联合给药时无需调整 FRUZAQLA 的剂量。 FRUZAQLA对其他药品的药代动力学影响作为 P-糖蛋白 (P-gp) 底物的医药产品单剂量150 mg达比加群酯 (dabigatran etexilate，一种 P-gp 受质) 与单剂量5 mg FRUZAQLA 联合给药，使达比加群的 AUC降低 9%。与FRUZAQLA抑制剂联合给药时无需调整 P-gp 底物的剂量。作为乳腺耐药蛋白 (BCRP) 底物的医药产品单次 10 mg 剂量的瑞舒伐他汀 (rosuvastatin，一种 BCRP 底物) 与单次 5 mg 剂量的FRUZAQLA 联合给药，使瑞舒伐他汀的 AUC 降低 19%。与 FRUZAQLA抑制剂联合给药时无需调整 BCRP底物的剂量。不良反应：FRUZAQLA 最常见的不良反应是：十分常见 (发生率≥1/10) 血小板计数降低、甲状腺功能减退、厌食、高血压、发声困难、腹泻、口腔炎、天门冬氨酸转氨酶升高、总胆红素升高、丙氨酸转氨酶升高、掌跖红肿感觉综合征、骨骼肌肉痛、关节痛、蛋白尿、疲乏和乏力常见 (≥1/100 至<1/10) 肺炎、上呼吸道感染、细菌感染、白血球减少、嗜中性白血球减少、低血钾、鼻出血、咽喉疼痛、胃肠道出血、胃肠道穿孔、胰酶升高、口腔疼痛、皮疹、黏膜炎关于美国处方信息： https://www.fruzaqla.com/sites/default/files/resources/fruzaqla-prescribing-information.pdf 关于日本处方信息： https://www.pmda.go.jp/PmdaSearch/iyakuDetail/ResultDataSetPDF/400256_42910H0M1028_1_01 关于欧盟处方信息： https://www.ema.europa.eu/en/documents/product-information/fruzaqla-epar-product-information_en.pdf 参考资料： [1] Bray F, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 Countries. CA Cancer J Clin. 2024;74(3):229-263. doi:10.3322/caac.21834. [2] Ferlay J, et al. Global Cancer Observatory: Cancer Today. Lyon, France: International Agency for Research on Cancer. Available from: https://gco.iarc.who.int/today, accessed 12 June 2024. [3] American Cancer Society. Cancer Facts & Figures 2024. Atlanta, American Cancer Society; 2024. [4] Bando H, et al. Therapeutic landscape and future direction of metastatic colorectal cancer. Nat Rev Gastroenterol Hepatol 2023; 20(5)306‑322. doi:10.1038/s41575‑022‑00736‑1. [5] D'Haene N, et al. Clinical application of targeted next‑generation sequencing for colorectal cancer patients: a multicentric Belgian experience. Oncotarget. 2018;9(29):20761‑20768. Published 2018 Apr 17. doi:10.18632/oncotarget.25099. [6] Venderbosch S, et al. Mismatch repair status and BRAF mutation status in metastatic colorectal cancer patients: A pooled analysis of the CAIRO, CAIRO2, COIN, and FOCUS Studies. Clinical Cancer Res. 2014; 20(20):5322–5330. doi:10.1158/1078‑0432.ccr‑14‑0332. [7] Koopman M, et al. Deficient mismatch repair system in patients with sporadic advanced colorectal cancer. Br J Cancer. 2009;100(2), 266–273. doi:10.1038/sj.bjc.6604867. [8] Ahcene Djaballah S, et al. HER2 in Colorectal Cancer: The Long and Winding Road From Negative Predictive Factor to Positive Actionable Target. Am Soc Clin Oncol Educ Book. 2022;42:1‑14. doi:10.1200/EDBK_351354. [9] Dasari NA, et al. Fruquintinib versus placebo in patients with refractory metastatic colorectal cancer (FRESCO‑2): an international, multicentre, randomised, double‑blind, Phase III study. Lancet. 2023;402(10395):41‑53. doi:10.1016/S0140‑6736(23)00772‑9. [10] Li J, et al. Effect of Fruquintinib vs Placebo on Overall Survival in Patients With Previously Treated Metastatic Colorectal Cancer: The FRESCO Randomized Clinical Trial. JAMA. 2018;319(24):2486-2496. DOI:10.1001/jama.2018.7855. 前瞻性陈述本新闻稿包含1995年《美国私人证券诉讼改革法案》"安全港"条款中定义的前瞻性陈述。这些前瞻性陈述反映了和黄医药目前对未来事件的预期，包括但不限于对于呋喹替尼用于治疗结直肠癌患者的治疗潜力的预期，以及呋喹替尼针对此适应症及其他适应症的进一步临床研究计划。前瞻性陈述涉及风险和不确定性。此类风险和不确定性包括下列假设：支持呋喹替尼于欧洲等地区获批用于治疗结直肠癌或其他适应症的上市许可申请的数据充足性、获得监管部门审批的潜力，呋喹替尼的安全性、和黄医药及/或武田为呋喹替尼进一步临床开发计划及商业化提供资金并实现及完成的能力，此类事件发生的时间，各方满足许可协议的条款和条件的能力，监管机构的行动或可影响临床试验的启动、时间和进展及呋喹替尼的注册路径，以及武田成功开发和商业化呋喹替尼的能力等。此外，由于部分研究依赖与其他药物产品与呋喹替尼联合使用，因此此类风险和不确定性包括有关这些治疗药物的安全性、疗效、供应和持续监管批准的假设。当前和潜在投资者请勿过度依赖这些前瞻性陈述，这些陈述仅在截至本新闻稿发布当日有效。有关这些风险和其他风险的进一步讨论，请查阅和黄医药向美国证券交易委员会、香港联合交易所有限公司以及AIM提交的文件。无论是否出现新讯息、未来事件或情况或其他因素，和黄医药均不承担更新或修订本新闻稿所含讯息的义务。医疗信息本新闻稿所提到的产品可能并未在所有国家上市，或可能以不同的商标进行销售，或用于不同的病症，或采用不同的剂量，或拥有不同的效力。本文中所包含的任何信息都不应被看作是任何处方药的申请、推广或广告，包括那些正在研发的药物。和黄医药（纳斯达克/伦敦证交所：HCM；香港交易所：13）是一家处于商业化阶段的创新型生物医药公司，致力于发现、全球开发和商业化治疗癌症和免疫性疾病的靶向药物和免疫疗法。集团旗下公司共有约5,000名员工，其中核心的肿瘤/免疫业务拥有约1,800人的团队。自成立以来，和黄医药致力于将自主发现的候选药物带向全球患者，首三个药物已在中国上市，其中首个药物亦于美国、欧洲和日本获批。欲了解更多详情，请访问：www.hutch-med.com/sc 。

临床3期引进/卖出上市批准

2024-12-13

·GlobeNewswire-Health Care

HUTCHMED to Receive Milestone Payment from Takeda following First European Reimbursement for FRUZAQLA® (fruquintinib)

— US$10 million milestone payment to HUTCHMED follows first national reimbursement in Europe — — Follows June 2024 European approval of FRUZAQLA® (fruquintinib), the first novel oral targeted therapy in the EU for metastatic colorectal cancer regardless of biomarker status in over a decade — HONG KONG and SHANGHAI and FLORHAM PARK, N.J., Dec. 12, 2024 (GLOBE NEWSWIRE) -- HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq/AIM:HCM; HKEX:13) today announces that it will receive a US$10 million milestone payment by its partner Takeda (TSE:4502/NYSE:TAK). Takeda received a national reimbursement recommendation for FRUZAQLA® (fruquintinib) for patients with previously treated metastatic colorectal cancer (“CRC”) in Spain in December 2024, the first national reimbursement recommendation in Europe. CRC is the second most common cause of cancer-related deaths in Europe. FRUZAQLA® was approved by the European Commission (“EC”) of the European Union (“EU”) in June 2024. Takeda has the exclusive worldwide license to further develop, commercialize and manufacture fruquintinib outside of mainland China, Hong Kong and Macau. “We are delighted for both our partner, Takeda, and patients in Spain who will now be able to receive reimbursement for this innovative treatment. This is an important step forward in improving patient access across Europe more broadly,” said Dr Weiguo Su, Chief Executive Officer and Chief Scientific Officer of HUTCHMED. “It also underscores our ongoing collaboration with Takeda and reinforces our shared commitment to addressing the needs of patients with metastatic colorectal cancer.” The approvals by the EC were primarily based on results from the Phase III multiregional FRESCO-2 trial. Data from FRESCO-2 were published in The Lancet in June 2023. FRUZAQLA® was approved in the US in November 2023, in the EU in June 2024, in Switzerland in August 2024, in Canada, Japan and the United Kingdom in September 2024 and in Argentina, Australia and Singapore in October 2024. Regulatory applications are progressing in many other jurisdictions. About CRC CRC is a cancer that starts in either the colon or rectum. According to the International Agency for Research on Cancer/World Health Organization, CRC is the third most prevalent cancer worldwide, associated with more than 1.9 million new cases and 900,000 deaths in 2022. In Europe, CRC was the second most common cancer in 2022, with approximately 538,000 new cases and 248,000 deaths.1,2 In the US, it is estimated that 153,000 patients will be diagnosed with CRC and 53,000 deaths from the disease will occur in 2024.3 In Japan, CRC was the most common cancer, with an estimated 146,000 new cases and 60,000 deaths, in 2022.2 Although early-stage CRC can be surgically resected, metastatic CRC remains an area of high unmet need with poor outcomes and limited treatment options. Some patients with metastatic CRC may benefit from personalized therapeutic strategies based on molecular characteristics; however, most patients have tumors that do not harbor actionable mutations.4,5,6,7,8 About Fruquintinib Fruquintinib is a selective oral inhibitor of all three VEGF receptors (VEGFR-1, -2 and -3). VEGFR inhibitors play a pivotal role in inhibiting tumor angiogenesis. Fruquintinib was designed to have enhanced selectivity that limits off-target kinase activity, allowing for drug exposure that achieves sustained target inhibition and flexibility for potential use as part of a combination therapy. About Fruquintinib Approvals Global regulatory submissions are based on data from two large, randomized, controlled Phase III trials, the global, multi-regional FRESCO-2 trial and the FRESCO trial conducted in China, showing consistent benefit among a total of 734 patients treated with fruquintinib. Safety profiles were consistent across trials. Results from the FRESCO-2 trial were published in The Lancet in June 2023,9 while results from the FRESCO trial were published in The Journal of the American Medical Association, JAMA.10 In mainland China, Hong Kong and Macau, fruquintinib is co-marketed by HUTCHMED and Eli Lilly and Company under the brand name ELUNATE®. It was included in the China National Reimbursement Drug List (NRDL) in January 2020. Since its launch in China, over 100,000 patients with colorectal cancer have been treated with fruquintinib. About HUTCHMED HUTCHMED (Nasdaq/AIM:HCM; HKEX:13) is an innovative, commercial-stage, biopharmaceutical company. It is committed to the discovery and global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. It has approximately 5,000 personnel across all its companies, at the center of which is a team of about 1,800 in oncology/immunology. Since inception it has focused on bringing cancer drug candidates from in-house discovery to patients around the world, with its first three medicines marketed in China, the first of which is also approved in the US, Europe and Japan. For more information, please visit: www.hutch-med.com or follow us on LinkedIn. E.U. IMPORTANT SAFETY INFORMATION Please consult the FRUZAQLA (fruquintinib) Summary of Product Characteristics (SmPC) before prescribing. Guidance for use: FRUZAQLA should be initiated by a physician experienced in the administration of anticancer therapy. Patients should be given the package leaflet. CONTRAINDICATIONS: Hypersensitivity to the active substance or to any of the excipients. SPECIAL POPULATIONS: Renal impairment: No dose adjustment is required for patients with mild, moderate, or severe renal impairment; Hepatic impairment: No dose adjustment is required for patients with mild or moderate hepatic impairment. FRUZAQLA is not recommended for use in patients with severe hepatic impairment as FRUZAQLA has not been studied in this population; Elderly: No dose adjustment is required in patients aged 65 years or above; Pediatric population: There is no relevant use of FRUZAQLA in the pediatric population for the indication of metastatic colorectal cancer; Women of childbearing potential / Contraception in females: Women of childbearing potential should be advised to use highly effective contraception during treatment and for at least 2 weeks following the last dose of FRUZAQLA; Pregnancy: There are no clinical data available on the use of FRUZAQLA in pregnant women. Based on its mechanism of action, FRUZAQLA has the potential to cause fetal harm. Animal studies have shown reproductive toxicity, including fetal malformations. FRUZAQLA should not be used during pregnancy unless the clinical condition of the woman requires treatment with FRUZAQLA. If FRUZAQLA is used during pregnancy or if the patient becomes pregnant while on treatment, the patient must be informed of the potential hazard to the fetus; Breast-feeding: The safe use of FRUZAQLA during breast-feeding has not been established. It is not known whether FRUZAQLA or its metabolites are excreted in human milk. There are no animal data on the excretion of FRUZAQLA in animal milk. A risk to the breastfeeding newborns/infants cannot be excluded. Breastfeeding should be discontinued during treatment and for 2 weeks after the last dose; Fertility: There are no data on the effects of FRUZAQLA on human fertility. Results from animal studies indicate that FRUZAQLA may impair male and female fertility. SPECIAL WARNINGS AND PRECAUTIONS FOR USE Hypertension: Hypertension, including hypertensive crisis, has been reported in patients treated with FRUZAQLA. Pre-existing hypertension should be monitored and adequately controlled in accordance with standard medical practices before starting FRUZAQLA treatment. Hypertension should be medically managed with antihypertensive medicinal products and adjustment of the FRUZAQLA dose, if necessary. FRUZAQLA should be permanently discontinued for hypertension that cannot be controlled with antihypertensive therapy or in patients with hypertensive crisis. Hemorrhagic events: Hemorrhagic events have been reported in patients treated with FRUZAQLA, including gastrointestinal (GI) tract events. Serious and sometimes fatal bleeding events have been reported in patients after treatment with FRUZAQLA. Hematologic and coagulation profiles should be monitored in accordance with standard medical practices in patients at risk for bleeding, including those treated with anticoagulants or other concomitant medicinal products that increase the risk of bleeding. In the event of severe bleeding requiring immediate medical intervention, FRUZAQLA should be permanently discontinued. Gastrointestinal perforation: GI perforation events, including fatal events, have been reported in patients treated with FRUZAQLA. Symptoms of GI perforation should be periodically monitored during treatment with FRUZAQLA. FRUZAQLA should be permanently discontinued in patients developing GI perforation. Proteinuria: Proteinuria events have occurred in patients treated with FRUZAQLA. Proteinuria should be monitored before initiation and during treatment with FRUZAQLA in accordance with standard medical practices. If urine dipstick proteinuria ≥ 2 g / 24 hours is detected, dose interruptions, adjustments, or discontinuation may be necessary. FRUZAQLA should be permanently discontinued in patients developing nephrotic syndrome. Palmar-plantar erythrodysesthesia syndrome (PPES): PPES is the most frequently reported dermatological adverse reaction. If Grade ≥2 skin reactions are detected, dose interruptions, adjustments, or discontinuation may be necessary. Posterior reversible encephalopathy syndrome (PRES): PRES has been reported in 1 patient (0.1%) treated with FRUZAQLA in clinical studies. PRES is a rare neurologic disorder that can present with headache, seizure, lethargy, confusion, altered mental function, blindness, and other visual or neurological disturbances, with or without associated hypertension. A diagnosis of PRES requires confirmation by brain imaging, preferably magnetic resonance imaging (MRI). In patients developing PRES, discontinuation of FRUZAQLA, along with control of hypertension and supportive medical management of other symptoms, are recommended.Impaired wound healing: Impaired wound healing has been reported in 1 patient (0.1%) treated with FRUZAQLA in clinical studies. Patients are recommended to withhold FRUZAQLA for at least 2 weeks prior to surgery. FRUZAQLA should not be resumed for at least 2 weeks after surgery, as clinically indicated when there is evidence of adequate wound healing. Arterial and venous thromboembolic events: It is recommended to avoid starting treatment with FRUZAQLA in patients with a history of thromboembolic events (including deep vein thrombosis and pulmonary embolism) within the past 6 months or if they have a history of stroke and/or transient ischemic attack within the last 12 months. If arterial thrombosis is suspected, FRUZAQLA should be discontinued immediately. INTERACTIONS Effects of other medicinal products on the pharmacokinetics of FRUZAQLA CYP3A inducers Co-administration of FRUZAQLA with rifampicin (a strong CYP3A inducer) 600 mg once daily decreased FRUZAQLA AUCinf by 65% and decreased Cmax by 12%. The concomitant use of FRUZAQLA with strong and moderate CYP3A inducers should be avoided. CYP3A inhibitors Co-administration of FRUZAQLA with itraconazole (a strong CYP3A inhibitor) 200 mg twice daily did not result in clinically meaningful changes in the area under the concentration-time curve (AUC) and Cmax of FRUZAQLA. No dose adjustment of FRUZAQLA is needed during concomitant use with CYP3A inhibitors. Gastric acid lowering agents Co-administration of FRUZAQLA with rabeprazole (a proton pump inhibitor) 40 mg once daily did not result in clinically meaningful changes in the AUC of FRUZAQLA. No dose adjustment of FRUZAQLA is needed during concomitant use with gastric acid lowering agents. Effect of FRUZAQLA on the pharmacokinetics of other medicinal products Medicinal products that are substrates of P-glycoprotein (P-gp) Co-administration of a single dose of dabigatran etexilate 150 mg (a P-gp substrate) with a single dose of FRUZAQLA 5 mg decreased AUC of dabigatran by 9%. No dose adjustment is recommended for P-gp substrates during concomitant use with FRUZAQLA. Medicinal products that are substrates of breast cancer resistance protein (BCRP) Co-administration of a single 10 mg dose of rosuvastatin (a BCRP substrate) with a single 5 mg dose of FRUZAQLA decreased AUC of rosuvastatin by 19%. No dose adjustment is recommended for BCRP substrates during concomitant use with FRUZAQLA. UNDESIRABLE EFFECTS: The most commonly reported adverse reactions with FRUZAQLA are: Very common(frequency ≥1/10)Thrombocytopenia, hypothyroidism, anorexia, hypertension, dysphonia, diarrhea, stomatitis, aspartate aminotransferase increased, total bilirubin increased, alanine aminotransferase increased, palmar-plantar erythrodysesthesia syndrome, musculoskeletal discomfort, arthralgia, proteinuria, asthenia, and fatigueCommon(≥1/100 to <1/10)Pneumonia, upper respiratory tract infection, bacterial infections, leukopenia, neutropenia, hypokalemia, epistaxis, throat pain, gastrointestinal hemorrhage, gastrointestinal perforation, pancreatic enzymes increased, oral pain, rash, and mucosal inflammation For US Prescribing Information: https://www.fruzaqla.com/sites/default/files/resources/fruzaqla-prescribing-information.pdf For Japan Prescribing Information: https://www.pmda.go.jp/PmdaSearch/iyakuDetail/ResultDataSetPDF/400256_42910H0M1028_1_01 For EU Prescribing Information: https://www.ema.europa.eu/en/documents/product-information/fruzaqla-epar-product-information_en.pdf Forward-Looking Statements This press release contains forward-looking statements within the meaning of the “safe harbor” provisions of the US Private Securities Litigation Reform Act of 1995. These forward-looking statements reflect HUTCHMED’s current expectations regarding future events, including its expectations regarding the therapeutic potential of fruquintinib for the treatment of such patients with CRC and the further clinical development of fruquintinib in this and other indications. Forward-looking statements involve risks and uncertainties. Such risks and uncertainties include, among other things, assumptions regarding the sufficiency of clinical data to support approval of fruquintinib for the treatment of patients with CRC or other indications in jurisdictions such as Europe, its potential to gain approvals from regulatory authorities, the safety profile of fruquintinib, HUTCHMED and/or Takeda’s ability to fund, implement and complete its further clinical development and commercialization plans for fruquintinib, the timing of these events, each party’s ability to satisfy the terms and conditions under the license agreement; actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials or the regulatory pathway for fruquintinib; and Takeda’s ability to successfully develop and commercialize fruquintinib. In addition, as certain studies rely on the use of other drug products as combination therapeutics with fruquintinib, such risks and uncertainties include assumptions regarding the safety, efficacy, supply and continued regulatory approval of these therapeutics. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. For further discussion of these and other risks, see HUTCHMED’s filings with the US Securities and Exchange Commission, The Stock Exchange of Hong Kong Limited and on AIM. HUTCHMED undertakes no obligation to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise. Medical Information This press release contains information about products that may not be available in all countries, or may be available under different trademarks, for different indications, in different dosages, or in different strengths. Nothing contained herein should be considered a solicitation, promotion or advertisement for any prescription drugs including the ones under development. CONTACTS Investor Enquiries+852 2121 8200 /ir@hutch-med.com Media Enquiries Ben Atwell / Alex Shaw, FTI Consulting+44 20 3727 1030 / +44 7771 913 902 (Mobile) / +44 7779 545 055 (Mobile) /HUTCHMED@fticonsulting.comZhou Yi, Brunswick+852 9783 6894 (Mobile) /HUTCHMED@brunswickgroup.com Nominated Advisor Atholl Tweedie / Freddy Crossley / Rupert Dearden, Panmure Liberum+44 (20) 7886 2500 ___________________________ 1Bray F,et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 Countries.CA Cancer J Clin.2024;74(3):229-263. doi:10.3322/caac.21834.2Ferlay J,et al. Global Cancer Observatory: Cancer Today. Lyon, France: International Agency for Research on Cancer. Available from:https://gco.iarc.who.int/today, accessed 12 June 2024.3American Cancer Society. Cancer Facts & Figures 2024. Atlanta,American Cancer Society; 2024.4Bando H, et al. Therapeutic landscape and future direction of metastatic colorectal cancer.Nat Rev Gastroenterol Hepatol2023; 20(5)306-322. doi:10.1038/s41575-022-00736-1.5D'Haene N, et al. Clinical application of targeted next-generation sequencing for colorectal cancer patients: a multicentric Belgian experience.Oncotarget.2018;9(29):20761-20768. Published 2018 Apr 17. doi:10.18632/oncotarget.25099.6Venderbosch S, et al. Mismatch repair status and BRAF mutation status in metastatic colorectal cancer patients: A pooled analysis of the CAIRO, CAIRO2, COIN, and FOCUS Studies.Clinical Cancer Res.2014; 20(20):5322–5330. doi:10.1158/1078-0432.ccr-14-0332.7Koopman M, et al. Deficient mismatch repair system in patients with sporadic advanced colorectal cancer.Br J Cancer.2009;100(2), 266–273. doi:10.1038/sj.bjc.6604867.8Ahcene Djaballah S, et al. HER2 in Colorectal Cancer: The Long and Winding Road From Negative Predictive Factor to Positive Actionable Target.Am Soc Clin Oncol Educ Book.2022;42:1-14. doi:10.1200/EDBK_351354.9Dasari NA, et al. Fruquintinib versus placebo in patients with refractory metastatic colorectal cancer (FRESCO-2): an international, multicentre, randomised, double-blind, Phase III study.Lancet.2023;402(10395):41-53. doi:10.1016/S0140-6736(23)00772-9.10Li J,et al. Effect of Fruquintinib vs Placebo on Overall Survival in Patients With Previously Treated Metastatic Colorectal Cancer: The FRESCO Randomized Clinical Trial.JAMA. 2018;319(24):2486-2496. DOI:10.1001/jama.2018.7855.

上市批准临床3期免疫疗法临床结果引进/卖出

100 项与利福平相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D00211	利福平	J04AB02	DB01045

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
细胞内鸟分枝杆菌感染	日本	Daiichi Sankyo Co., Ltd.	2011-05-20
非结核分枝杆菌感染	日本	Daiichi Sankyo Co., Ltd.	2011-05-20
嗜血杆菌感染	澳大利亚	Sanofi-Aventis Australia Pty Ltd.	2009-01-21
脑膜炎球菌感染	美国	Sanofi-Aventis U.S. LLC	1989-05-25
麻风	中国	四川省长征药业股份有限公司	1981-01-01
麻风	中国	茂祥集团吉林制药有限公司	1981-01-01
麻风	中国	四川彩虹制药有限公司	1981-01-01
麻风	中国	成都第一制药有限公司	1981-01-01
麻风	中国	国药控股股份有限公司	1981-01-01
麻风	中国	成都通德药业有限公司	1981-01-01
结核	中国	成都第一制药有限公司	1981-01-01
结核	中国	四川彩虹制药有限公司	1981-01-01
结核	中国	国药控股股份有限公司	1981-01-01
结核	中国	四川省长征药业股份有限公司	1981-01-01
结核	中国	成都通德药业有限公司	1981-01-01
结核	中国	茂祥集团吉林制药有限公司	1981-01-01
脑膜炎	美国	Oxford Pharmaceuticals LLC	1971-05-21
肺结核	美国	Oxford Pharmaceuticals LLC	1971-05-21

未上市

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适应症	最高研发状态	国家/地区	公司	日期
假体关节感染	临床3期	法国	Sanofi	2009-04-01
多发性硬化症	临床1期	美国	Sanofi	2020-05-18
自身免疫性疾病	临床1期	英国	Kadmon Corp. LLC	2018-04-09
糖尿病	临床1期	法国	Sanofi	2017-02-27
额颞痴呆	临床前	美国	medilabo RFP, Inc.	2023-03-07

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临床结果

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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


NCT04918771 (CTgov)	临床3期	病毒性呼吸道感染	435	Raphamin (Raphamin)	網選網獵鬱淵積觸積憲(夢築網鹽選壓夢廠蓋襯) = 鏇鹽觸醖願構壓餘網顧簾夢蓋窪憲憲構艱積壓 (壓壓願壓顧遞鹽膚夢蓋, 餘蓋窪衊淵願鹹齋齋壓 ~ 範淵窪網鏇鑰糧憲壓顧) 更多	-	2024-10-15
				Placebo (Placebo)	網選網獵鬱淵積觸積憲(夢築網鹽選壓夢廠蓋襯) = 蓋築鹽齋鏇顧遞淵鬱蓋簾夢蓋窪憲憲構艱積壓 (壓壓願壓顧遞鹽膚夢蓋, 範糧選築鬱襯範簾顧齋 ~ 壓築網構獵網廠憲艱顧) 更多
NCT04021121 (ALTER, CTgov)	临床2期	脑膜结核	40	High dose RIF+LZD (High Dose RIF With LZD)	蓋鏇膚淵夢遞齋鹽繭積(選壓簾憲鹽襯築鹽糧簾) = 獵艱遞積網顧構襯鏇齋醖選壓顧醖衊鹹憲餘選 (糧糧蓋醖衊觸獵憲顧範, 糧遞膚壓齋艱憲膚選製 ~ 醖鑰窪顧網糧艱膚鹹製) 更多	-	2024-10-01
				Standard dose RIF+LZD (Standard Dose RIF With LZD)	蓋鏇膚淵夢遞齋鹽繭積(選壓簾憲鹽襯築鹽糧簾) = 積積蓋構鹹繭網憲齋顧醖選壓顧醖衊鹹憲餘選 (糧糧蓋醖衊觸獵憲顧範, 積積襯築夢艱餘簾蓋鬱 ~ 蓋積膚齋積壓鹽糧網壓) 更多
NCT04485156 (Pubmed \| Tuberc Respir Dis (Seoul)) 人工标引	临床3期	肺结核	58	rifampicinrisoniazid,pyrazinamideand pyrazinamide	網鏇鏇壓齋製艱簾網壓(積遞襯蓋積網膚顧鹹範) = 選繭鹹願遞淵構願築廠鬱糧選鹽餘願獵膚憲獵 (簾鹹鹽鑰鏇構獵網膚壓 )	不佳	2024-09-27
				Standard 6-month regimen	網鏇鏇壓齋製艱簾網壓(積遞襯蓋積網膚顧鹹範) = 構網觸鹹淵鏇醖窪繭憲鬱糧選鹽餘願獵膚憲獵 (簾鹹鹽鑰鏇構獵網膚壓 )
ATS2024	N/A	-	-	Rifampin	觸繭膚夢願窪獵衊齋築(鏇鏇夢鬱選壓餘淵夢蓋) = progressive liver failure 壓醖鹹蓋襯窪願繭膚艱 (遞蓋壓蓋鏇廠餘鹹獵醖 ) 更多	-	2024-05-19
AUA2024	N/A	-	-	RIFAMPIN (Sacral neuromodulation (SNM) device biofilms)	鏇願夢製範製艱衊餘襯(艱願艱醖鏇網糧獵蓋顧) = 觸選淵餘膚遞願範壓範鹹構襯憲蓋遞衊醖顧壓 (構製糧齋鏇構齋憲願顧 )	-	2024-05-01
NCT03988933 (Pubmed) 人工标引	临床2期	结核一线	1,368	rifampicinose group (10 mg/kg once daily for 4 months)	淵觸淵夢醖範製淵簾餘(齋窪蓋糧製鏇糧鬱鹽繭) = 蓋醖餘網構選艱淵襯鏇壓蓋襯膚艱淵製醖膚網 (廠鑰襯積餘鑰蓋積遞鏇 )	不佳	2024-03-26
				rifampicinroup (20 mg/kg daily for 2 months)	淵觸淵夢醖範製淵簾餘(齋窪蓋糧製鏇糧鬱鹽繭) = 獵夢衊網餘夢夢糧願淵壓蓋襯膚艱淵製醖膚網 (廠鑰襯積餘鑰蓋積遞鏇 )
NCT04525235 (Pubmed \| Antimicrob Agents Chemother)	临床1期	肺结核	25	RIF40	淵壓壓鹹製鏇繭顧鏇壓(齋憲齋醖襯艱衊壓夢願) = 築衊餘糧醖壓膚廠廠鹹顧製衊淵壓觸糧積壓壓 (醖齋衊窪鏇積艱鑰鬱遞, 96 ~ 115) 更多	积极	2023-10-18
NCT03174184 (COMRADE, CTgov)	临床2期	肺结核	112	MEROPENEM 2 grams TID+Rifampin+Amoxicillin/Clavulanate Potassium 500 MG-125 MG Oral Tablet (Rifampin Resistant A)	夢顧壓遞衊製憲獵壓繭(蓋鏇鹹選範蓋淵選蓋艱) = 齋齋憲衊鹹膚積鑰廠膚壓憲網積糧鏇構蓋壓積 (衊簾艱選壓築積衊繭襯, 衊鏇鏇鹽膚廠簾膚範獵 ~ 醖選憲艱憲網選觸廠艱) 更多	-	2023-07-19
				MEROPENEM 2 grams TID+Amoxicillin/Clavulanate Potassium 500 MG-125 MG Oral Tablet (Rifampin Resistant B)	夢顧壓遞衊製憲獵壓繭(蓋鏇鹹選範蓋淵選蓋艱) = 鹽壓積醖築蓋衊淵夢鬱壓憲網積糧鏇構蓋壓積 (衊簾艱選壓築積衊繭襯, 觸夢夢醖願鹽鏇鹽繭淵 ~ 簾窪艱鏇範遞觸選築選) 更多
NCT02256696 (CTgov)	临床2期	肺结核	157	PA-824+Rifampin+Isoniazid+Pyrazinamide (Arm 1)	衊襯積願膚積窪壓壓齋(餘簾窪艱顧繭淵鏇鬱鹽) = 遞構獵鹽顧鹽窪繭膚齋觸夢窪願鬱廠廠憲鹽獵 (選窪繭願鹽鹹襯醖餘願, 蓋衊積築積夢觸憲鹽廠 ~ 願糧鑰製鹽範襯糧齋選) 更多	-	2023-07-18
				PA-824+Rifabutin+Isoniazid+Pyrazinamide (Arm 2)	衊襯積願膚積窪壓壓齋(餘簾窪艱顧繭淵鏇鬱鹽) = 壓鬱鹽鹽憲簾積壓製願觸夢窪願鬱廠廠憲鹽獵 (選窪繭願鹽鹹襯醖餘願, 窪築衊繭壓製鏇廠願積 ~ 夢簾獵繭餘獵壓窪齋鬱) 更多
ALTER trial (S25.003) (AAN2023)	临床2期	脑膜结核 HIV	23	Linezolid 1200 mg	築積築積鬱構積製鑰餘(衊獵蓋鹹糧積淵膚糧構) = n=1 觸顧蓋鹹窪遞憲築襯窪 (壓鬱醖餘積鑰網齋鹽壓 ) 更多	-	2023-04-25
				High-dose rifampin