Bictegravir/Emtricitabine/Tenofovir Alafenamide Fumarate

▎药明康德内容团队编辑 只需每年一针，长效HIV预防疗法挺进3期临床 吉利德科学（Gilead Sciences）公司日前公布了两种每年一次的lenacapavir配方，作为暴露前预防（PrEP）疗法，在1期临床试验中的积极结果。数据支持每年一次lenacapavir用于PrEP的未来开发。该结果已发表于医学期刊《柳叶刀》。吉利德科学公司计划于2025年下半年启动3期临床试验。 1期临床试验数据显示，每年一次、肌肉注射的两种lenacapavir配方达到并维持了超出在3期临床试验PURPOSE 1和PURPOSE 2试验中观察到的与HIV预防疗效相关的血浆浓度。此前报道的PURPOSE 1和PURPOSE 2数据显示，每年两次皮下注射lenacapavir在降低HIV感染方面显示出优于背景HIV发病率和每日一次口服Truvada。 两种配方的受试者血浆中lenacapavir浓度在至少56周内均高于95%有效浓度。此外，两种每年一次lenacapavir配方在第52周的中位谷浓度（分别为57.0 ng/mL和65.6 ng/mL）均高于PURPOSE 1和PURPOSE 2试验中每年两次lenacapavir在第26周观察到的23.4 ng/mL。 Lenacapavir是一种“first-in-class”长效HIV病毒衣壳抑制剂，可以干扰HIV病毒衣壳蛋白的组装和拆卸，在病毒生命周期的多个阶段发挥作用。它已经获得美国FDA授予的突破性疗法认定，用于HIV病毒感染暴露前预防。2024年，《科学》期刊也将lenacapavir评为年度科学突破，表示这一“first-in-class”药物为艾滋病的长效治疗与预防带来了新的曙光。 维持HIV病毒抑制48周，默沙东双药疗法达两项3期临床主要终点 默沙东（MSD）公司今日宣布，在研每日一次口服双药方案doravirine/islatravir（DOR/ISL）在两项关键性3期试验中获得积极结果。在两项试验中，DOR/ISL与活性对照组相比达到非劣效性标准。基于这些积极结果，默沙东计划在2025年中期启动向监管机构提交上市申请。 在双盲试验MK-8591A-052中，主要终点（HIV-1 RNA≥50拷贝/毫升）结果显示，在接受克替拉韦/恩曲他滨/替诺福韦艾拉酚胺（BIC/FTC/TAF）治疗下已实现病毒抑制的成人患者中，第48周切换至DOR/ISL的受试者中有1.5%病毒载量达到或超过50拷贝/毫升，而BIC/FTC/TAF组为0.6%（治疗差异0.9%，95% CI：-1.9，2.9）。第48周切换至DOR/ISL的受试者中有91.5%维持了病毒抑制，而继续接受BIC/FTC/TAF治疗的受试者中这一比例为94.2%（治疗差异-2.6%，95% CI：-7.1，2.6）。 在开放标签试验MK-8591A-051中，在接受基线抗病毒治疗（bART）并获得病毒抑制的成人患者中，第48周切换接受DOR/ISL治疗的受试者中有1.4%病毒载量达到或超过50拷贝/毫升，而继续接受bART治疗的患者这一数值为4.9%（治疗差异-3.6%，95% CI：-7.8，-0.8）。第48周切换至DOR/ISL的受试者中有95.6%维持了病毒抑制，而继续接受bART的受试者中这一比例为91.9%（治疗差异3.7%，95% CI：-0.3，8.9）。 4个月一次，长效HIV抗体疗法组合3期临床结果积极 ViiV Healthcare今日宣布，其长效HIV抗体疗法N6LS，在2b期临床试验EMBRACE中取得积极结果。数据显示，每四个月一次给药的N6LS，与每月一次长效cabotegravir（CAB LA）联用，可成功使已稳定接受治疗的HIV成年患者保持病毒抑制，并且耐受性良好。 EMBRACE研究在六个月主要终点时的结果显示，静脉注射60 mg/kg的N6LS组中96%的受试者，以及皮下注射3000 mg的N6LS组中88%的受试者维持了HIV-1 RNA水平低于50拷贝/毫升，而标准治疗组为96%。 基于试验中观察到的积极结果，ViiV Healthcare将在EMBRACE的第二部分试验中，进一步评估六个月一次静脉注射N6LS与CAB LA联用的效果。 罗氏合作开发潜在“best-in-class”胰淀素类似物 Zealand Pharma今日宣布，与罗氏（Roche）达成全球合作及许可协议，共同开发Zealand Pharma的胰淀素类似物petrelintide，作为体重管理的基石性疗法，同时迅速扩展至相关适应症。新闻稿指出，petrelintide具有成为“best-in-class”疗法的潜力。 根据协议，双方将共同开发和商业化petrelintide及其组合产品，包括petrelintide与罗氏的潜在“best-in-class”胰高血糖素样肽-1（GLP-1）、葡萄糖依赖性促胰岛素多肽（GIP）受体双重激动剂CT-388构成的固定剂量组合产品。双方将在美国和欧洲共同商业化petrelintide及本次合作产生的其他产品，而罗氏获得全球其他地区的独家商业化权益。Zealand Pharma可在美国和欧洲参与最多50%的商业化活动。 Zealand Pharma将获得16.5亿美元的前期付款。Zealand Pharma还将有资格获得12亿美元的研发里程碑付款（主要与petrelintide单药治疗3期临床试验启动相关）及24亿美元的销售里程碑付款。 Petrelintide为一种长效胰淀素类似物，适合每周一次皮下注射。该药物在设计时注重化学和物理稳定性，在中性pH值下无纤维化现象，从而可与其他肽类药物实现联合配方及联合给药。 超9亿美元助力反义寡核苷酸疗法开发 Ono Pharmaceutical（ONO）宣布已与Ionis Pharmaceuticals签订许可协议，获得反义寡核苷酸（ASO）疗法sapablursen的开发及商业化权益。Sapablursen是一种用于治疗真性红细胞增多症（PV）的在研ASO药物，目前正在2期临床试验IMPRSSION中针对成人PV患者进行评估。Sapablursen已于2024年1月获得美国FDA授予的快速通道资格，并于2024年8月获得孤儿药资格。 根据协议，ONO将获得全球范围内开发和商业化sapablursen的独家许可。Ionis将继续负责完成正在进行的2期临床试验IMPRSSION，而ONO将全权负责后续开发、监管申报及商业化工作。ONO将支付2.8亿美元前期付款，并根据达到研发、监管及销售里程碑，支付高达6.6亿美元的额外里程碑付款。 Sapablursen的设计旨在降低TMPRSS6基因编码的跨膜蛋白酶丝氨酸6的产生，从而增加铁稳态关键调控因子铁调素（hepcidin）的表达。通过提高铁调素的产生，sapablursen有望对真性红细胞增多症等血液疾病产生积极影响。 ▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放 参考资料： [1] First Clinical Data for Gilead’s Investigational Once-Yearly Lenacapavir for HIV Prevention Presented at CROI 2025 and Published in The Lancet. Retrieved March 12, 2025, from https://www.gilead.com/news/news-details/2025/first-clinical-data-for-gileads-investigational-once-yearly-lenacapavir-for-hiv-prevention-presented-at-croi-2025-and-published-in-the-lancet [2] Merck Announces Positive Data from Phase 3 Trials that Show the Investigational, Once-Daily, Oral, Two-Drug Regimen of Doravirine/Islatravir (DOR/ISL) Maintained HIV-1 Viral Suppression at Week 48. Retrieved March 12, 2025, from https://www.merck.com/news/merck-announces-positive-data-from-phase-3-trials-that-show-the-investigational-once-daily-oral-two-drug-regimen-of-doravirine-islatravir-dor-isl-maintained-hiv-1-viral-suppression-at-week-48/ [3] ViiV HEALTHCARE’S INVESTIGATIONAL BROADLY NEUTRALISING ANTIBODY - N6LS - SUCCESSFULLY MAINTAINS VIRAL SUPPRESSION IN LONG-ACTING TREATMENT OF HIV. Retrieved March 12, 2025, from https://viivhealthcare.com/hiv-news-and-media/news/press-releases/2025/march/investigational-broadly-neutralising-antibody/ [4] Zealand Pharma and Roche enter collaboration and license agreement to co-develop and co-commercialize petrelintide as a future foundational therapy for people with overweight and obesity. Retrieved March 12, 2025, from https://www.globenewswire.com/news-release/2025/03/12/3041113/0/en/Zealand-Pharma-and-Roche-enter-collaboration-and-license-agreement-to-co-develop-and-co-commercialize-petrelintide-as-a-future-foundational-therapy-for-people-with-overweight-and-o.html [5] Ono Enters into License Agreement with Ionis Pharmaceuticals for Sapablursen for the Treatment of Polycythemia Vera. Retrieved March 12, 2025, from https://www.businesswire.com/news/home/20250311080840/en 免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。 版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。 分享，点赞，在看，聚焦全球生物医药健康创新

– Long-Term Outcomes Reinforce the High Efficacy of Biktarvy ® in People with HIV and HBV Coinfection – – Investigational Long-Acting, Twice-Yearly Treatment Regimen of Lenacapavir and Broadly Neutralizing Antibodies (bNAbs) Meets Primary Endpoint in Phase 2 Study and Gains Breakthrough Therapy Designation – – Late-Breaker Oral Presentation of Phase 2 Results from the First HIV Cure Clinical Trial Conducted in South Africa – FOSTER CITY, CA, USA I March 12, 2025 I Gilead Sciences, Inc. (Nasdaq: GILD) today announced the presentation of late-breaking data and multiple oral presentations from its innovative HIV treatment portfolio and pipeline at the Conference on Retroviruses and Opportunistic Infections (CROI 2025). The new findings reflect a transformative portfolio and a rapidly advancing forward-looking pipeline focused on expanding choices and enhancing outcomes for those with HIV, while continuing to reach towards a cure. “Gilead is fueling the next wave of innovation in HIV to help end the epidemic globally,” said Jared Baeten, MD, PhD, Senior Vice President, Virology Therapeutic Area Head. “Our contributions to CROI spotlight our dedication to scientific discovery, reflect our commitment to addressing the diverse treatment needs and preferences of communities affected by HIV and underscore the vital importance of catalyzing research reaching towards a cure.” Biktarvy Demonstrates High Rates of Viral Suppression in People with HIV/HBV Coinfection ALLIANCE ( NCT03547908 ) is an ongoing Phase 3 study evaluating Biktarvy versus dolutegravir 50 mg (DTG) + emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg, F/TDF, DTG+F/TDF, in adults with HIV-1/HBV co-infection initiating treatment. The ALLIANCE trial is the first randomized clinical trial of TAF- vs TDF-based regimens in treatment naïve adults with HIV/HBV coinfection. Its goal is to evaluate treatment regimens that may effectively suppress both HIV and HBV. Previously reported results demonstrated the efficacy of both antiretroviral regimens. New outcomes were presented at CROI. Week 48 outcomes from the open-label extension phase following the 96-week randomized phase reported on the longer-term efficacy and safety of the investigational use of Biktarvy in adults with HIV/HBV coinfection initiating treatment. The newly presented data shows that Biktarvy maintained high rates of HIV-1 (95.4%) and HBV (86.6%) virologic suppression, defined as HIV RNA <50 copies/ mL and HBV DNA <29 IU/ mL, respectively, in participants (n=89) following a switch to Biktarvy after 96 weeks of treatment with DTG+ F/TDF. Study drug-related treatment-emergent adverse events (TEAEs) were reported in 19% of participants and most were mild to moderate, with zero discontinuations due to TEAEs. The most commonly reported study drug–related TEAEs were weight gain (9%) and low-density lipoprotein (LDL) cholesterol increased (3%). These data demonstrate the high rates of viral suppression by Biktarvy in adults with both HIV-1 and HBV switching their treatment to Biktarvy. The use of Biktarvy in individuals with HIV/HBV co-infection is investigational and the safety and efficacy of this use have not been established. Breakthrough Therapy Designation Awarded to Long-Acting, Twice-Yearly Investigational Treatment Combination Regimen of Lenacapavir and Broadly Neutralizing Antibodies (bNAbs) In January 2025, the FDA granted lenacapavir (LEN) with bNAbs (teropavimab [GS-5423, TAB] and zinlirvimab [GS-2872, ZAB]) Breakthrough Therapy Designation, which is intended to expedite the development of new drugs that may demonstrate substantial improvement over available therapy. LEN+TAB+ZAB (LTZ) harbors the potential to be the first long-acting combination treatment regimen with twice-yearly dosing. At CROI 2025, the primary results of a Phase 2 study evaluating the investigational combination of LTZ were presented during an oral session and featured in the press program; those data announced at CROI confirm previously presented Phase 1b results. The Phase 2 ( NCT05729568 ) open-label study from Gilead’s long-acting treatment pipeline evaluated the treatment response of participants receiving the investigational combination of LTZ. Efficacy and safety results were evaluated when virologically suppressed adults switched to LTZ every 6 months versus staying on stable baseline oral antiretroviral regimen. The study met its primary endpoint, which is the proportion of participants with HIV-1 RNA ≥ 50 copies/mL at Week 26 as determined by the US FDA-defined snapshot algorithm. The Week 26 data demonstrated the high efficacy of the LTZ regimen, with 96% (n=51 of 53) of participants who received LTZ and 96% (n=26 of 27) who received SBR remained virologically suppressed. CD4 cell counts also increased from baseline to week 26 in both groups, with a mean change of +23/μL (n=143) with LTZ and +69/μL (n=203) with SBR. The most common AEs with LTZ were injection site reactions related to subcutaneous LEN administration. There were no serious adverse events (AEs) related to LTZ; there were no infusion reactions related to TAB or ZAB. One participant in the SBR arm discontinued the study due to a serious treatment-related AE. Teropavimab and zinlirvimab are investigational compounds. The use of these compounds in combination with lenacapavir are investigational. They are not approved by the U.S. Food and Drug Administration or any other regulatory authority for any use, alone or in combination with lenacapavir. Their safety and efficacy are unknown. The use of lenacapavir in virologically suppressed people with HIV is investigational and the safety and efficacy of this use have not been established. Landmark HIV Cure Clinical Trial Conducted in South Africa Results from the first HIV cure trial to be conducted in South Africa, sponsored by Gilead, demonstrated that complex cure studies can be successfully conducted, alongside community, in resource-limited settings where great unmet need exists. As part of Gilead’s efforts to find a cure for HIV, the Phase 2a GS-US-382-5445 trial ( NCT05281510 ) enrolled 20 South African cisgender women from the FRESH (Females Rising through Education, Support, and Health) cohort who had received antiretroviral therapy (ART) soon after acquiring HIV and were virologically suppressed for at least 12 months. Participants received up to 10 oral doses of Gilead’s investigational TLR7 agonist, vesatolimod, every 2 weeks starting on day 0, plus IV infusions of broadly neutralizing antibodies (bNAbs) VRC07-523LS and CAP256V2LS, provided by the National Institutes of Health (NIH), on day 7. Participants began an analytical treatment interruption (ATI) on Day 35 and remained off ART until Week 48, or until they met restart criteria. Participants who reached week 48 without meeting ART restart criteria had the option of remaining off ART through the end of study follow-up at Week 60. Results presented at CROI showed the treatment combination was generally well-tolerated with no treatment-related serious adverse events (TEAEs) reported. The most common study TEAEs were infusion-related reactions (n = 18; 16 grade 1, 2 grade 2). Seventy percent of participants (n=14) met ART restart criteria. Thirty percent (n=6) remained off ART through Week 48, of which 4 remained off ART through Week 60. While the data suggest that the trial regimen alone is not sufficient as an HIV cure regimen, the mechanistic learnings will inform the development of future cure approaches. There is currently no cure for HIV or AIDS. Vesatolimod, VRC07-523LS and CAP256V2LS are investigational compounds. They are not approved by the U.S. Food and Drug Administration or any other regulatory authority for any use, alone or in combination. Their safety and efficacy are unknown. Please see below for U.S. Indications and Important Safety Information, including Boxed Warning , for Biktarvy. About Lenacapavir Lenacapavir is approved in multiple countries for the treatment of adults with multi-drug resistant HIV in combination with other antiretrovirals. The use of lenacapavir for HIV prevention is investigational and the safety and efficacy of lenacapavir for this use have not been established. The multi-stage mechanism of action of lenacapavir is distinguishable from other currently approved classes of antiviral agents. While most antivirals act on just one stage of viral replication, lenacapavir is designed to inhibit HIV at multiple stages of its lifecycle and has no known cross resistance exhibited in vitro to other existing drug classes. Lenacapavir is being evaluated as a long-acting option in multiple ongoing and planned early and late-stage clinical studies in Gilead’s HIV prevention and treatment research program. Lenacapavir is being developed as a foundation for potential future HIV therapies with the goal of offering both long-acting oral and injectable options with several dosing frequencies, in combination or as a mono agent, that help address individual needs and preferences of people and communities affected by HIV. Science Magazine named lenacapavir its 2024 “Breakthrough of the Year.” About Biktarvy Biktarvy is a complete HIV treatment that combines three powerful medicines to form the smallest 3-drug, integrase strand transfer inhibitor (INSTI)-based single-tablet regimen (STR) available, offering simple once-daily dosing with or without food, with a limited drug interaction potential and a high barrier to resistance. Biktarvy combines the novel, unboosted INSTI bictegravir with the F/TAF backbone. Biktarvy is a complete STR and should not be taken with other HIV medicines. U.S. Indication for Biktarvy Biktarvy (bictegravir 50 mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg) is indicated as a complete regimen for the treatment of HIV-1 infection in adults and pediatric patients weighing at least 14 kg who have no antiretroviral (ARV) treatment history or to replace the current ARV regimen in those who are virologically-suppressed (HIV-1 RNA <50 copies per mL) on a stable ARV regimen with no known or suspected substitutions associated with resistance to bictegravir or tenofovir. About Gilead HIV 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, and cancer. Gilead operates in more than 35 countries worldwide, with headquarters in Foster City, California. For more than 35 years, Gilead has been a leading innovator in the field of HIV, driving advances in treatment, prevention and cure research. Gilead researchers have developed 12 HIV medications , including the first single-tablet regimen to treat HIV, the first antiretroviral for pre-exposure prophylaxis (PrEP) to help reduce new HIV infections, and the first long-acting injectable HIV treatment medication administered twice-yearly. Our advances in medical research have helped to transform HIV into a treatable, preventable, chronic condition for millions of people. Gilead is committed to continued scientific innovation to provide solutions for the evolving needs of people affected by HIV around the world. Through partnerships , collaborations and charitable giving, the company also aims to improve education, expand access and address barriers to care, with the goal of ending the HIV epidemic for everyone, everywhere. Gilead has been repeatedly recognized as one of the top two leading philanthropic funders of HIV-related programs in a report released by Funders Concerned About AIDS. SOURCE: Gilead Sciences