2019年3月
专注开发HIV/AIDS药物的ViiV Healthcare公布新型长效注射HIV疗法(cabotegravir/rilpivirine,CAB/RPV)(每月一次肌肉注射给药)关键III期临床研究FLAIR(临床登记号:NCT02938520),ATLAS (NCT02951052)的48周数据。
2019年CROI会议上公布的FLAIR相关数据显示:cabotegravir/rilpivirine与HIV复方药Triumeq(abacavir/dolutegravir/lamivudine,ABC/DTG/3TC)(多替拉韦/阿巴卡韦/拉米夫定)相比,CAB/RPV在维持HIV-1成人感染者病毒学抑制方面具有非劣效性(病毒学抑制率)。
FLAIR临床研究针对HIV-1初治患者,最开始需要接受DTG/ABC/3TC口服方案诱导治疗20周。在16周时HIV-1 RNA<50拷贝/毫升患者按照1:1比例分为针剂组和继续口服方案组,48周时病毒学无应答率,HIV-1 RNA≥50拷贝/毫升的患者比例针剂组非劣效于口服方案组(2.1% vs 2.5%);病毒学抑制率,HIV-1 RNA<50拷贝/毫升的患者比例针剂组非劣效于口服方案组(93.6% vs 93.3%)(265/283 vs264/283)。
双药长效注射制剂,每月一次:cabotegravir长效制剂(CAB LA)为一款新型整合酶抑制剂(长效纳米混悬液, long-acting nanoformulated)(integrase inhibitor ),rilpivirine长效制剂(RPV LA)为非核苷类逆转录酶抑制剂(non-nucleoside reverse transcriptase inhibitor )。两个单独的肌内注射药物,臀部是首选的注部位。
2019年4月
ViiV Healthcare向美国FDA递交新型长效注射HIV疗法(cabotegravir/rilpivirine)新药上市申请(NDA)。
2019年6月
美国FDA授予cabotegravir/rilpivirine新药上市申请(NDA)优先审评(Priority Review)资格。这一操作,将使原本常规审评时间10个月,缩短为6个月。批准日期此前预计在2019年12月29日。如果本款疗法获批,将HIV治疗从每年给药365天变为12次,大大提高患者的依从性。
2019年12月
ViiV Healthcare在2019年12月21日宣布,收到美国FDA的完整答复函(complete response letter ,CRL),HIV长效cabotegravir/rilpivirine复方药物上市申请被拒绝批准。FDA表示是因为该复方药物Chemistry Manufacturing and Controls (CMC)原因。此次被否,跟产品的临床试验数据和安全性无关。ViiV Healthcare将与美国FDA密切沟通,来完善进一步的NDA申请。
2020年3月
3月18日,加拿大卫生部(Health Canada)批准了ViiV Healthcare的Cabenuva®(cabotegravir/rilpivirine)上市,属于全球范围内首次准。另外,加拿大批准了cabotegravir片剂,用于长效疗法的导入治疗。
同样在3月,Cabenuva®(cabotegravir/rilpivirine)的多项临床结果发表在NEJM上。
2020年9月,ViiV Healthcare宣布Cabenuva®(cabotegravir/rilpivirine)在加拿大市场正式推出。期待本款长效疗法给患者带来更完善的治疗方案。
ViiV Healthcare 艾滋病药物在研产品线(HIV Pipeline)
附:
Cabotegravir其他名称或代号: 744 LA, CAB, GSK-1265744, GSK1265744, GSK744, GSK744 LA, GSK744 LAP, S-265744, S/GSK1265744, cabotegravir LA, cab等等。下图为其结构式:
Cabotegravir其他在展开的临床:https://pubchem.ncbi.nlm.nih.gov/compound/54713659#section=Clinical-Trials。
参考:
NMPA/CDE;
药融圈数据;
FDA/EMA;
相关公司公开披露;
https://viivhealthcare.com;
https://adisinsight.springer.com/search;
https://viivhealthcare.com/en-gb/our-medicines/medicines-in-development/;
Long-Acting Cabotegravir and Rilpivirine for Maintenance of HIV-1 Suppression. NEJM, DOI: 10.1056/NEJMoa1904398;
https://viivhealthcare.com/en-gb/media/press-releases/2020/march/viiv-healthcare-announces-first-global-regulatory-approval-of-ca/;
UNAIDS. Global HIV & AIDS Statistics — 2019 Fact Sheet. Available at: http://www.unaids.org/en/resources/fact-sheet.Last accessed November 2019;
ViiV Healthcare receives complete response letter from US FDA for use of investigational cabotegravir and rilpivirine long-acting regimen in the treatment of HIV;
https://viivhealthcare.com/en-gb/media/press-releases/2019/december/complete-response-letter-from-us-fda/;
https://aidsinfo.nih.gov/drugs/513/cabotegravir/0/patient,美国NIH;
HIV在研新药,National Institute of Allergy and Infectious Diseases (NIAID)。 NIAID ChemDB, HIV Drugs in Development. https://chemdb.niaid.nih.gov/DrugDevelopmentHIV.aspx. Accessed March 22, 2019;
ViiV Healthcare 官网。 Medicines in development. https://www.viivhealthcare.com/our-medicines/medicines-in-development.aspx. Accessed March 22, 2019;
https://www.viivhealthcare.com/en-gb/media/press-releases/2019/july/viiv-healthcare-announces-start-of-first-ever-study-to-identify-and-evaluate-approaches-to-implementing-its-once-monthly-injectable-hiv-treatment-in-clinical-practice/;
https://www.viivhealthcare.com/en-gb/media/press-releases/2019/april/viiv-healthcare-submits-new-drug-application-to-us-fda-for-the-first-monthly-injectable-two-drug-regimen-of-cabotegravir-and-rilpivirine-for-treatment-of-hiv/;
GSK1265744 (Cabotegravir, CAB) for named patient/compassionate use in HIV. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US)。 Registered on March 5, 2018. NLM Identifier: NCT03462810. https://www.clinicaltrials.gov/ct2/show/NCT03462810. Accessed March 22, 2019;
http://www.croiconference.org/sites/default/files/posters-2015/554LB.pdf. Accessed March 22, 2019;
Margolis DA, Gonzalez-Garcia J, Stellbrink H-J, et al. Long-acting intramuscular cabotegravir and rilpivirine in adults with HIV-1 infection (LATTE-2): 96-week results of a randomised, open-label, phase 2b, non-inferiority trial. The Lancet. 2017;390(10101):1499-1510;
等等。
文章来源:药融圈
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