Emtricitabine/Tenofovir Disoproxil 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

– Phase 1 Data Indicate Potential for Use of Once-Yearly Lenacapavir for HIV Prevention, with Plans to Launch a Phase 3 Trial in 2H 2025 – – Also at CROI: New PURPOSE 1 Data Showcasing Preference for Twice-Yearly Lenacapavir vs. Once-Daily Orals and In-Depth Look at Adolescent Pharmacokinetic, Safety and Efficacy Data – FOSTER CITY, CA, USA I Marcch 11, 2025 I Gilead Sciences, Inc. (Nasdaq: GILD) today presented the first data from its ongoing Phase 1 study investigating two novel, once-yearly formulations of lenacapavir, the company’s injectable HIV-1 capsid inhibitor, for the investigational use of HIV prevention as pre-exposure prophylaxis (PrEP). The data were presented during an oral abstract session at the Conference on Retroviruses and Opportunistic Infections (CROI 2025) and were also published today in The Lancet . Data will support the future development of once-yearly lenacapavir for PrEP, for which Gilead plans to launch a Phase 3 study in the second half of 2025. The Phase 1 study data showed that the two different formulations of once-yearly lenacapavir administered via intramuscular injection achieved and maintained plasma concentrations exceeding those associated with HIV prevention efficacy observed in the Phase 3 PURPOSE 1 trial ( NCT04994509 ) and PURPOSE 2 trial ( NCT04925752 ). The previously reported PURPOSE 1 and PURPOSE 2 data showed that twice-yearly subcutaneous lenacapavir demonstrated superiority at reducing HIV infections when compared to background HIV incidence (bHIV) and once-daily oral Truvada® (emtricitabine 200mg and tenofovir disoproxil fumarate 300mg; F/TDF) in a broad and geographically diverse range of people. “Gilead is continuing to innovate in our work to develop additional person-centered long-acting injectable and oral options to help people find an HIV prevention choice that is right for them,” said Jared Baeten, MD, PhD, Senior Vice President, Virology Therapeutic Area Head, Gilead Sciences. “Once-yearly lenacapavir, if approved, could become an important new HIV prevention option that could help address PrEP adherence and persistence challenges for individuals who need or want PrEP around the world.” Promising once-yearly lenacapavir for PrEP pharmacokinetic profiles over 52 weeks The Phase 1 study evaluated the pharmacokinetics, safety and tolerability of two intramuscular single-dose 5000mg lenacapavir formulations. The trial included 40 healthy adults at low risk of HIV acquisition, between the ages of 18 and 55 years, with a body mass index of less than or equal to 35.0 kg/m 2 . Lenacapavir plasma concentrations for participants remained above the 95% effective concentration for at least 56 weeks with both formulations. Furthermore, median trough concentrations of both formulations of once-yearly lenacapavir at Week 52 (57.0 ng/mL and 65.6 ng/mL) were higher than those observed with twice-yearly lenacapavir in the PURPOSE 1 and PURPOSE 2 trials at Week 26 (23.4 ng/mL). Data from the study confirmed that both once-yearly formulations of lenacapavir warrant further investigation. Safety data demonstrated both formulations of once-yearly lenacapavir for PrEP were well tolerated, with no new safety signals Once-yearly lenacapavir is being investigated as an intramuscular injection. This is different from the subcutaneous formulation of lenacapavir, which is being investigated for twice-yearly dosing. The most commonly reported adverse event for both intramuscular formulations studied was injection site pain, which was mostly mild in severity and resolved within 1 week (occurred in 80% of participants receiving formulation 1, and 75% receiving formulation 2), and was reduced by pretreatment with an ice pack. Medication-emergent adverse events were similar between the two cohorts and mostly mild to moderate in severity. New PrEP modality preference data demonstrate preference for twice-yearly lenacapavir vs. once-daily orals in PURPOSE 1 survey participants New quantitative survey data and late-breaking qualitative survey data from the PURPOSE 1 trial, evaluating twice-yearly subcutaneous lenacapavir for PrEP among cisgender women in sub-Saharan Africa, were also presented at CROI in two poster sessions. An interim analysis of surveys included 2,561 trial participants’ self-reported preferences for twice-yearly lenacapavir for PrEP injections and once-daily pills, with approximately two-thirds of survey respondents preferring twice-yearly lenacapavir at Week 52 of their trial participation, compared to fewer than one-third of respondents preferring once-daily pills. Additionally, at Week 52, most respondents (61%) reported they would feel more protected from HIV with twice-yearly PrEP injections compared with once-daily pills, and 61% of respondents also reported they would feel more confident about not missing a PrEP dose with twice-yearly injections compared with once-daily pills. Qualitative data among 108 participants also showed that respondents, particularly adolescents aged 16 and 17 years, noted that twice-yearly injections better suited their lifestyles compared with once-daily pills. New study population data from PURPOSE 1 show comparable pharmacokinetic and safety profiles for both adolescent and adult trial participants Additional adolescent-related data from the PURPOSE 1 trial were also presented at CROI yesterday during an oral abstract session and press conference. PURPOSE 1 is the first adult Phase 3 HIV prevention trial to intentionally include adolescents aged 16 and 17 years, and trial enrollment was much higher than in typical adolescent-dedicated studies (124 adolescents, 56 of whom were assigned to the lenacapavir group). The data showed that observed lenacapavir plasma concentrations were comparable between adolescent and adult trial groups, with participants in both groups experiencing the same most common adverse events. There were zero incident HIV infections across the adolescent and adult groups receiving lenacapavir. Given these results, data submitted to regulatory authorities support the potential use of twice-yearly lenacapavir for adolescents who need or want PrEP The use of lenacapavir for the prevention of HIV is investigational and has not been determined to be safe or efficacious and is not approved anywhere globally. There is currently no cure for HIV or AIDS. 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 the PURPOSE Program Gilead’s landmark PURPOSE program is the most comprehensive and diverse HIV prevention trial program ever conducted. The program comprises five HIV prevention trials around the world that are focused on innovation in science, trial design, community engagement and health equity. The PURPOSE trials are evaluating the safety and efficacy of an investigational, twice-yearly injectable medicine, lenacapavir, to reduce the chance of getting HIV. The Phase 2 and 3 program, consisting of PURPOSE 1-5, is assessing the potential of lenacapavir to help a diverse range of people around the world who could benefit from PrEP. More information about the PURPOSE program, including individual trial descriptions, populations and locations, can be found at www.purposestudies.com . About Gilead HIV 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 was recognized as one of the leading philanthropic funders of HIV-related programs in a report released by Funders Concerned About AIDS. SOURCE: Gilead Sciences