Doravirine

▎药明康德潜在首款！FDA受理默沙东HIV双药疗法上市申请默沙东（MSD）今日宣布，美国FDA已受理其为所开发的在研复方口服药物doravirine/islatravir（DOR/ISL）所提交的新药申请（NDA）。这是一款每日一次的双药方案，用于治疗病毒学抑制的HIV-1感染成人患者。该申请的PDUFA日期为2026年4月28日。根据新闻稿，如获批准，DOR/ISL将成为在关键3期试验中显示出疗效不劣于基于整合酶链转移抑制剂（INSTI）三联复方治疗方案的首个双药方案。此次新药申请基于两项关键3期临床试验（MK-8591A-051和MK-8591A-052）第48周的数据。在MK-8591A-051试验中，DOR/ISL在开放标签设计下展现出不劣于基线抗病毒治疗（bART）的疗效；而在随机双盲对照的MK-8591A-052试验中，该方案亦被证实不劣于基于INSTI的三联复方治疗方案克替拉韦/恩曲他滨/替诺福韦艾拉酚胺（BIC/FTC/TAF）。两项研究中，DOR/ISL的安全性概况整体与对照治疗方案相当，支持其作为一种简化治疗的新选项，有望助力HIV治疗方案进一步优化。不会致幻！小分子疗法获FDA授予突破性疗法认定Transcend Therapeutics今日宣布，美国FDA已授予其在研药物TSND-201突破性疗法认定，用于治疗创伤后应激障碍（PTSD）。该认定是基于其IMPACT-1关键性2期临床试验的积极结果，标志着TSND-201有望为PTSD患者带来更快速和持久的治疗获益。TSND-201是一种快速起效的神经重塑因子（neuroplastogen），具有明确的药理学特征，其主要作用位点是单胺转运蛋白，对5HT-2a无活性（即不会致幻）。IMPACT-1是一项随机、安慰剂对照的2期临床试验，共有65名患有重度PTSD的患者入组。研究显示，TSND-201能显著、快速且持续改善PTSD症状：至第10天，患者的创伤后应激障碍量表CAPS-5评分在安慰剂调整后改善达-8.00分，并在第64天持续至-9.64分。该药物在试验中表现出良好的耐受性，未观察到幻觉等不良精神反应，亦无患者因不良事件而中断治疗。近20亿美元！艾伯维囊获潜在“first-in-class”三特异性抗体艾伯维（AbbVie）今日宣布与Ichnos Glenmark Innovation旗下的IGI Therapeutics达成一项独家许可协议，获得由其专有BEAT蛋白平台所开发的主打疗法ISB 2001在肿瘤及自身免疫疾病领域的全球开发与商业化权利。根据协议条款，艾伯维将获得ISB 2001在北美、欧洲、日本及大中华区的独家开发、生产与销售权。IGI将获得7亿美元首付款，并有望根据后续开发、监管和商业进展，额外获得最多12.25亿美元的里程碑付款。ISB 2001是一款潜在“first-in-class”、靶向CD38/BCMA/CD3的三特异性抗体，该疗法目前正在1期临床试验中，针对复发/难治性多发性骨髓瘤（R/R MM）患者进行评估。该平台突破了传统双特异性抗体的工程瓶颈，通过专有的通用轻链库与基于T细胞受体（TCR）界面的重链配对机制，BEAT平台能够构建结构更接近天然抗体的多特异性抗体，提升其稳定性与功能。该平台具备广泛的多特异性设计能力，可针对多个抗原招募多种免疫细胞类型，包括包括T细胞、髓系细胞和自然杀伤（NK）细胞，从而为肿瘤免疫治疗和自身免疫疾病提供具有前景的新一代免疫细胞接合药物。此次合作将进一步强化艾伯维在免疫治疗领域的布局，推动BEAT平台的临床转化与全球拓展。参考资料：[1] U.S. FDA Accepts New Drug Application for Merck’s Doravirine/Islatravir, an Investigational, Once-Daily, Oral, Two-Drug Regimen for Treatment of Adults with Virologically Suppressed HIV-1 Infection. Retrieved July 10, 2025 from https://www-merck-com.libproxy1.nus.edu.sg/news/u-s-fda-accepts-new-drug-application-for-mercks-doravirine-islatravir-an-investigational-once-daily-oral-two-drug-regimen-for-treatment-of-adults-with-virologically-suppressed-hiv-1-infe/[2] Transcend Therapeutics Receives Breakthrough Therapy Designation for TSND-201 (methylone) for the Treatment of PTSD. Retrieved July 10, 2025 from https://www.prnewswire.com/news-releases/transcend-therapeutics-receives-breakthrough-therapy-designation-for-tsnd-201-methylone-for-the-treatment-of-ptsd-302501928.html[3] AbbVie and Ichnos Glenmark Innovation (IGI) Announce Exclusive Global Licensing Agreement for ISB 2001, a First-in-Class CD38×BCMA×CD3 Trispecific Antibody. Retrieved July 10, 2025 from https://www.prnewswire.com/news-releases/abbvie-and-ichnos-glenmark-innovation-igi-announce-exclusive-global-licensing-agreement-for-isb-2001-a-first-in-class-cd38ObcmaOcd3-trispecific-antibody-302501835.html免责声明：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：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

Doravirine/islatravir would be the first FDA-approved two-drug regimen without an integrase inhibitor that demonstrated non-inferior efficacy and a generally comparable safety profile to the three-drug InSTI-based regimen, BIC/FTC/TAF, in a Phase 3 pivotal trial RAHWAY, NJ, USA I July 10, 2025 I Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced that the U.S. Food and Drug Administration (FDA) has accepted for review the New Drug Application (NDA) for doravirine/islatravir (DOR/ISL), an investigational, once-daily, oral, two-drug regimen for adults with HIV-1 infection that is virologically suppressed on antiretroviral therapy. The FDA has set a target action date of April 28, 2026, for the application under the Prescription Drug User Fee Act (PDUFA). “Merck has been at the forefront of HIV research for more than 35 years and we are pleased to continue our work to innovate and deliver new options that aim to meet the needs of the HIV community,” said Dr. Eliav Barr, senior vice president, head of global clinical development and chief medical officer, Merck Research Laboratories. “The health needs of people living with HIV often change over time – whether it’s managing comorbidities or navigating complex medication regimens. We believe DOR/ISL, if approved, will represent an important new complete regimen option designed to help meet their diverse needs.” The NDA is based on findings at Week 48 of two pivotal Phase 3 clinical trials ( MK-8591A-051 and MK-8591A-052 ) where DOR/ISL was demonstrated to be non-inferior to baseline antiretroviral therapy (bART) in the open-label trial MK-8591A-051 and non-inferior to bictegravir/emtrictabine/tenofovir alafenamide i [BIC/FTC/TAF (50mg/200mg/25mg)] in the double-blind trial MK-8591A-052. Across both trials, the safety profile of DOR/ISL was generally comparable to comparator baseline antiretroviral regimens in trial MK-8591A-051 and BIC/FTC/TAF in trial MK-8591A-052. Data from these trials were presented during the 2025 Conference on Retroviruses and Opportunistic Infections (CROI) in San Francisco. About the Phase 3 Trial MK-8591A-051 MK-8591A-051 is a Phase 3, open-label, randomized, active-controlled clinical trial evaluating the efficacy and safety of a switch to investigational, oral, once-daily DOR/ISL (100mg/0.25mg) in adults with HIV-1 infection that has been virologically suppressed using ART. The primary efficacy endpoint was the percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 48 (non-inferiority margin 4%). In this trial, 551 adults with HIV-1 RNA <50 copies/mL for three months or more on oral 2- or 3-drug ART, with no history of treatment failure and no known virologic resistance to DOR, were randomized 2:1 and switched to DOR/ISL (n=366) or continued bART (n=185), stratified by bART regimen. The median age of participants was 51 years; 39.7% were assigned female sex at birth, 45.4% were Black or African American, and 14.5% were Hispanic or Latine. At baseline, 64.2% were treated with an InSTI-based regimen, 30.3% with an NNRTI-based regimen, and 5.4% with a protease inhibitor (PI)-based regimen, with median duration on current ART of 3.8 years (IQR 2.0-6.3). About the Phase 3 Trial MK-8591A-052 MK-8591A-052 is a Phase 3, double-blind, randomized, active-controlled clinical trial to evaluate the efficacy and safety of a switch to investigational, oral, once-daily DOR/ISL (100mg/0.25mg) in adults with HIV-1 infection that has been virologically suppressed on BIC/FTC/TAF (50mg/200mg/25mg). The primary efficacy endpoint was the percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 48 (non-inferiority margin 4%). In this trial, 513 adults with HIV-1 who had virologic suppression for three months or more on BIC/FTC/TAF, no history of treatment failure and no known resistance to DOR were randomized (2:1) and switched to DOR/ISL (n=342) or continued treatment with BIC/FTC/TAF (n=171). The median age of participants was 47 years; 21.4% were assigned female sex at birth, 30.8% were Black or African American, and 22.8% were Hispanic or Latine. The median duration of BIC/FTC/TAF treatment prior to trial enrollment was 3.4 years (IQR 2.0-5.0). About Islatravir (MK-8591) and Merck’s HIV Research Islatravir (MK-8591), Merck’s investigational nucleoside reverse transcriptase translocation inhibitor (NRTTI), blocks HIV-1 replication by multiple mechanisms including inhibition of reverse transcriptase translocation, resulting in immediate chain termination and induction of structural changes in the viral DNA, resulting in delayed chain termination. Islatravir is under evaluation in multiple ongoing early and late-stage clinical trials in combination with other antiretrovirals for potential daily and once-weekly treatments for HIV-1, with islatravir serving as the anchor medicine in the treatment regimens based on its potency and resistance profile. In addition to the MK-8591A-051 and MK-8591A-052 trials, ongoing Phase 3 trials of daily DOR/ISL (100mg /0.25mg) include MK-8591A-053 in people with HIV who had not previously received treatment (treatment-naïve), and MK-8591A-054 evaluating open-label DOR/ISL (100 mg/0.25 mg) in individuals who participated in earlier Phase 3 trials of DOR/ISL (100 mg/0.75 mg). Islatravir in combination with Gilead’s lenacapavir is in Phase 3 development as a novel oral once-weekly treatment for HIV-1, and islatravir in combination with our company’s investigational non-nucleoside reverse transcriptase inhibitor (NNRTI) ulonivirine (MK-8507) is in Phase 2 development as an oral once-weekly treatment. Merck’s commitment to researching NRTTIs includes MK-8527, an investigational, novel oral, once-monthly NRTTI candidate that is in Phase 2 development for HIV-1 pre-exposure prophylaxis (PrEP). For an overview of Merck’s HIV treatment and prevention clinical development program, please click here . Merck’s Commitment to HIV For more than 35 years, Merck has been committed to scientific research and discovery in HIV leading to scientific breakthroughs that have helped change HIV treatment. Our work has helped pioneer the development of new options across multiple drug classes to help those impacted by HIV. Today, we are developing a series of antiviral options designed to help people manage their HIV and to help prevent HIV, with the goal of reducing the growing burden of infection worldwide. We want to ensure people are not defined by HIV, and our work focuses on transformational innovations, collaborations with others in the global HIV community, and access initiatives aimed at helping to end the HIV epidemic for everyone. Indications and usage for PIFELTRO ® (doravirine) and DELSTRIGO ® (doravirine, lamivudine, and tenofovir disoproxil fumarate) in the U.S. PIFELTRO is indicated in combination with other antiretroviral (ARV) agents for the treatment of HIV-1 infection in adult patients with no prior ARV treatment history or to replace the current ARV regimen in those who are virologically suppressed (HIV-1 RNA less than 50 copies per mL) on a stable ARV regimen with no history of treatment failure and no known substitutions associated with resistance to doravirine. DELSTRIGO is indicated as a complete regimen for the treatment of HIV-1 infection in adult patients with no prior ARV treatment history or to replace the current ARV regimen in those who are virologically suppressed (HIV-1 RNA less than 50 copies per mL) on a stable ARV regimen with no history of treatment failure and no known substitutions associated with resistance to the individual components of DELSTRIGO. About Merck At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.merck.com and connect with us on X (formerly Twitter) , Facebook , Instagram , YouTube and LinkedIn . SOURCE: Merck