Benvitimod

同写意20岁庆！第五届全球生物医药前沿技术大会报名开启！“意”同创新，穿越周期。7月中旬，苏州金鸡湖畔，让我们与“新药写意人”一起为中国医药创新“同写意”！在过去的十年间，随着中国研究的发展、基础设施的改善、制药行业生态系统的完善以及药品监管体系的改革，中国创新药物的研发水平得到了显著的提高。此外，中国制药公司通过在境外开展临床试验，也加快了融入全球药物研发企业的步伐。为了评估中国创新药物在美国的研发成果和现状，来自复旦大学药学院和美国Tufts药物研发中心的中美学者分析了ClinicalTrials.gov网站自2007年1月1日至2023年12月31日期间，中国创新药物在美国临床研发的数据。研究结果发表于Nature Reviews Drug Discovery（医学一区，影响因子120.1）。总体趋势从2007年到2023年，来自177家中国制药公司的350个创新药物在美国进行了691项临床试验，其中包括Ⅰ期试验339项（49%）、Ⅱ期试验269项（39%）、Ⅲ期试验83项（12%），共涵盖499个适应证。在此期间，在美国进行试验的6个中国创新药物获美国食品药品监督管理局（FDA）批准，用于10个适应证，这6个药物是：泽布替尼（2019年首次批准）、ciltacabtagene autoleucel（2022年）、本维莫德（2022年）、特瑞普利单抗（2023年）、呋喹替尼（2023年）及艾贝格司亭α（2023年）。中国创新药及其适应证350个创新药中，新分子实体182个（52%），新生物制剂162个（46%），中药6个（2%）。小分子药物（158/350；45%）和单克隆抗体（77/350；22%）是主要的治疗方式。双特异性抗体（28/350；8%）、抗体-药物偶联物（24/350；7%）以及细胞和基因治疗产品（19/350；5%）也成为重要的治疗药物类别（图1a）。肿瘤一直是中国药企的主要研发重点（图1b），其中230个（66%）创新药物在358项（72%）肿瘤适应证的临床试验中进行研究。排名前5位的肿瘤药物靶点为PD-1、EGFR、PD-L1、HER2和claudin 18.2。图1. 2007~2023年在美国开展临床试验的中国创新药物概况。a. 按形式（modality）分类的药物。b，按治疗领域划分的药物适应证。ADC，抗体-药物偶联物；mAb，单克隆抗体。 药物研发规划的趋势 从2019年到2023年，在美国进行的中国新药临床试验数量剧增，大多数（569/691; 82%）临床试验都是在此期间进行的（图2a）。Ⅰ期和Ⅱ期试验的增长速度最快，Ⅲ期试验的增长速度较慢，考虑到临床药物研发中典型的损耗率，这是符合预期的。然而，2021年之后，所有这三个期别的临床试验数目均有所下降，部分原因是COVID-19疫情所导致的研究中断。在美国进行的这691项临床试验中，481项（70%）由中国发起人公司申办，188项（27%）由国外合作者申办，22项（3%）由国内合作伙伴申办。由国外合作者申办的临床试验的比例随药物研发阶段的进展而增加，Ⅰ期仅占19%，Ⅲ期则增加到40%（2b）。图2. 美国临床试验中研究的中国创新药物研发规划的趋势。a. 每年启动的临床试验数量。B. 临床试验申办方。发起人（Originators）和国内合作者（Domestic collaborators）是总部设在中国的公司，国外合作者（Foreign collaborators）是总部设在其他地方的公司。临床成功率作者还分析跟踪了每种药物特定适应证的研发项目。从2007年到2023年，34家公司主导的75个研发项目（45个肿瘤项目，占60%）共发生了311个阶段转换。作者将药物研发过程中各个阶段的临床成功率定义为：从一个阶段进入下一个阶段的药物研发项目数除以所分析的时间段内更早期阶段启动并完成的项目总数。 如图3a所示，Ⅱ期成功率远低于任何其他阶段，仅为17%（15/88）；Ⅰ期和Ⅲ期成功率分别为41%（75/184）和36%（12/33）。成功率最高的是监管提交阶段，为67%。总体而言，从Ⅰ期一路走到美国FDA批准的复合概率为1.7%（41% × 17% × 36% × 67%）。此外，有14个药物研发项目进入了监管备案阶段但未在美国进行/完成Ⅲ期试验，其中7个获得美国FDA批准，成功率为50%（低于67%）。例如，ciltacabtagene autoleucel（cilta-cel）是一种靶向BCMA的CAR-T疗法，基于关键Ⅰb/Ⅱ期 CARTITUDE-1研究的数据，已获得美国FDA批准。作者还确定了新分子实体和新生物制剂研发项目各个阶段的成功率（图3b）。新生物制剂研发项目的Ⅰ期成功率远低于新分子实体研发项目，分别为16%（7/45）和49%（65/133）；而新生物制剂研发项目的Ⅲ期成功率高于新分子实体研发项目，分别为50%（8/16）和31%（4/13）。 图3. 在美国开展临床试验的中国创新药物的临床研发成功率。a. 每个阶段的成功概率。b. 每个阶段不同治疗类型的成功概率。BLA，生物许可申请。EUA，紧急使用授权。NDA，新药申请。前景该分析的结果表明，中国制药企业正在从仿制药生产商向创新药开发商转型，并取得进展，中国药品监管制度改革和加大对中国药品研发的投入也正在取得成果。努力关注创新质量、迈向多样化疗法和平台，对于将中国制药企业打造成全球药物研发企业的主要参与者，将具有非常重要的意义。参考文献：Ge Q, Zhang X, Kaitin KI, Shao L. Development of Chinese innovative drugs in the USA. Nat Rev Drug Discov. 2024 May 8. doi: 10.1038/d41573-024-00079-3. Epub ahead of print. PMID: 38720006.更多优质内容，欢迎关注↓↓↓

- sNDA filing acceptance is based on positive data from the Phase 3 ADORING 1 and ADORING 2 pivotal trials and interim results from the Phase 3 ADORING 3 open-label, long-term extension trial- - FDA PDUFA Action Expected in Q4 2024 - LONG BEACH, Calif. & BASEL, Switzerland--(BUSINESS WIRE)-- Dermavant Sciences Inc. a biopharmaceutical company dedicated to developing and commercializing innovative therapeutics in immuno-dermatology, today announced that the U.S. Food and Drug Administration (FDA) accepted the company’s Supplemental New Drug Application (sNDA) for VTAMA® (tapinarof) cream, 1% for the topical treatment of atopic dermatitis (AD) in adults and children 2 years of age and older. The Prescription Drug User Fee Act ("PDUFA") action date assigned by the Agency is in Q4 2024. VTAMA cream is a novel, aryl hydrocarbon receptor agonist in development as a once-daily, cosmetically elegant, and steroid-free, topical cream for both acute treatment and long-term management of AD. VTAMA cream, 1% is currently approved for the topical treatment of plaque psoriasis in adults in the U.S. and is the same strength and formulation being studied in the ADORING Phase 3 development program and included in the sNDA submission for AD. Atopic dermatitis, commonly referred to as eczema, is one of the most common inflammatory skin diseases that causes inflammation, intense itch, redness, and irritation of skin and impacts approximately 16.5 million adults and more than 9.6 million children in the U.S. Approximately 80% of individuals affected by atopic dermatitis experience disease onset prior to 6 years of age; if approved VTAMA cream may be available for children as young as 2 years old affected with atopic dermatitis. “The FDA acceptance of our sNDA is an important milestone in our efforts to bring VTAMA cream, as a potentially safe and well-tolerated non-steroidal treatment option, to adults and children as young as 2 years old who suffer from atopic dermatitis,” said Todd Zavodnick, Chief Executive Officer of Dermavant. “Our commitment to patients is unwavering, and we remain highly focused on preparing for the commercial launch of VTAMA cream, subject to FDA approval, for its second indication of atopic dermatitis.” The regulatory application is supported by positive Phase 3 data from ADORING 1 and ADORING 2, two identical, double-blind, randomized, vehicle-controlled, pivotal trials, as well as an open-label maximal usage pharmacokinetics (MUPK) trial in children aged 2-17 years, and the interim analysis results of ADORING 3, a Phase 3, 48-week, open-label, extension trial. On May 24, 2022, Dermavant announced the FDA approved VTAMA® (tapinarof) cream, 1% for the treatment of plaque psoriasis in adults. The approval made VTAMA cream the first non-steroidal topical novel chemical entity launched for psoriasis in the U.S. in more than 25 years. VTAMA cream is once-daily, cosmetically elegant, steroid-free, topical cream approved for mild, moderate, and severe plaque psoriasis in adults – with no label safety warnings or precautions, or restrictions on duration of use or body surface area. IMPORTANT SAFETY INFORMATION Indication: VTAMA® (tapinarof) cream, 1% is an aryl hydrocarbon receptor agonist indicated for the topical treatment of plaque psoriasis in adults. Adverse Events: The most common adverse reactions (incidence ≥ 1%) in subjects treated with VTAMA cream were folliculitis (red raised bumps around the hair pores), nasopharyngitis (pain or swelling in the nose and throat), contact dermatitis (skin rash or irritation, including itching and redness, peeling, burning, or stinging), headache, pruritus (itching), and influenza (flu). You are encouraged to report negative side effects of prescription drugs to the FDA. Visit or call 1-800-FDA-1088. See full Prescribing Information and Patient Information. About Dermavant’s Phase 3 Program for VTAMA cream in Atopic Dermatitis ADORING is Dermavant’s Phase 3 atopic dermatitis (AD) clinical development program for VTAMA® (tapinarof) cream, 1%, which consists of ADORING 1 (NCT05014568) and ADORING 2 (NCT05032859), as well as ADORING 3 (NCT05142774), a 48-week open-label, extension trial. About Atopic Dermatitis Atopic dermatitis (AD), commonly referred to as eczema, is one of the most common inflammatory skin diseases, affects over 26 million people in the U.S. alone and up to 10% of adults worldwide. AD occurs most frequently in children, affecting up to 20% worldwide. The disease results in itchy, red, swollen, and cracked skin, often affecting the folds of the arms, back of the knees, hands, face, and neck. Itching is an especially bothersome symptom in AD, and tends to worsen at night, disturbing sleep and causing fatigue, which in children can lead to inattention at school. People with AD may also experience social and emotional distress due to the visibility and discomfort of the disease. About Dermavant Dermavant Sciences, a subsidiary of Roivant Sciences, is a biopharmaceutical company dedicated to developing and commercializing innovative therapeutics in immuno-dermatology. Dermavant’s focus is to develop therapies that have the potential to address high unmet medical needs while driving greater efficiency in research and clinical development. The company’s medical dermatology pipeline includes earlier-development, late-stage and commercialized, product candidates that target specific unmet needs in two of the largest growing immuno-dermatology markets, plaque psoriasis and atopic dermatitis, as well as other immunological and inflammatory diseases. Dermavant is marketing VTAMA® (tapinarof) cream, 1%, for the topical treatment of plaque psoriasis in adults. The FDA approved VTAMA cream for the topical treatment of mild, moderate, and severe plaque psoriasis in May 2022. Dermavant has been developing VTAMA cream for the treatment of atopic dermatitis in adults and children 2 years of age and older and released positive topline results from its ADORING 1 and 2 pivotal Phase 3 clinical trials in 1H 2023. Dermavant’s pipeline includes DMVT-506, a next generation aryl hydrocarbon receptor (AhR) agonist under development as a potential treatment option for immunological and inflammatory diseases with multiple potential routes of administration. For more information, please visit and follow us on Twitter (@dermavant) and LinkedIn (Dermavant Sciences). ©2024 Dermavant Sciences, Inc. All Rights Reserved. All trademarks are the property of Dermavant Sciences, GmbH.