全球药物批准/研发动态 01 全球新药批准情况根据药渡数据统计分析，本次统计周期（2024.08.31-09.06）全球（不含中国）共有1个新药获批上市。其中，新适应症批准1个。与上个统计周期相比，本次减少9个批准新药。 9月5日，Travere Therapeutics宣布，FDA已完全批准FILSPARI（Sparsentan）用于减缓有疾病进展风险的原发性IgAN成人患者的肾功能下降。FILSPARI是唯一一种口服、每日一次的非免疫抑制药物，通过阻断IgAN疾病进展的两条关键途径（内皮素-1和血管紧张素II）直接靶向肾脏肾小球损伤。在对404名随机分配患者的最终分析中，与厄贝沙坦相比，FILSPARI显著降低了从基线到第110周的肾功能下降率。与活性对照厄贝沙坦相比，在第36周观察到的对蛋白尿的积极治疗效果在两年测量期内持续存在。PROTECT研究的其他结果表明，FILSPARI耐受性良好，具有明确定义的安全性。全球（不含中国）新药批准情况（部分） 02 全球新药申报进展根据药渡数据统计分析，本次统计周期（2024.08.31-09.06）全球（不含中国）共有3个新药申报上市。其中，NDA申报1个，BLA申报1个，细胞疗法1个。本次NDA/BLA申报数量与上次统计周期相同。 9月4日，AXSM宣布FDA已确认重新提交AXS-07的新药申请，用于治疗急性偏头痛。AXS-07由MoSEIC™美洛昔康和利扎曲坦组成。美洛昔康快速吸收，同时保持较长的血浆半衰期。美洛昔康是一种COX-2优先非甾体抗炎药，利扎曲坦是一种5-HT1B/1D激动剂。AXS-07旨在快速缓解偏头痛，减少症状复发。 NDA/BLA申报根据药渡数据统计分析，本次统计周期（2024.08.31-09.06）全球（不含中国）共有2个药物获监管机构特殊资格认定。其中，化学药1个，生物药1个。与上次统计周期相比，本次减少4个获监管机构特殊资格认定的药物。 9月4日，Actimed宣布FDA已授予S-oxprenolol（ACM-002）孤儿药资格认定，用于治疗肌萎缩侧索硬化症（ALS）。ALS是一种毁灭性的孤儿病，具有高度、未满足的医疗需求，S-oxprenolol在该适应症中生成的早期非临床数据表明，它可能在满足这一服务不足的患者群体的一些重要需求方面发挥潜在作用。同日，信达生物宣布其PD-1/IL-2α-bias双特异性抗体融合蛋白IBI363获得FDA授予快速通道资格，拟定适应症为既往接受过至少一线含PD-1/L1检查点抑制剂系统性治疗后进展的局部晚期或转移性黑色素瘤（脉络膜黑色素瘤除外）。IBI363是PD-1/IL-2双特异性融合蛋白，同时具有阻断PD-1/PD-L1通路和激活IL-2通路两项功能。在37例既往接受过免疫治疗的黑色素瘤患者接受了1mg/kg IBI363治疗并至少接受了一次基线后肿瘤评估的患者中，11例获得了客观缓解，包括1例CR和10例PR，ORR和DCR分别为29.7%和73.0%。特殊资格认定情况（部分） 03 全球新药研发进展根据药渡数据统计分析，本次统计周期（2024.08.31-09.06）全球（不含中国）新药临床研发状态更新共计27条，涉及肿瘤、血液和淋巴疾病、遗传代谢病、神经疾病以及免疫系统疾病等共计9个领域。其中，遗传和代谢领域及感染领域临床进展更新居各领域之首，均为5条：遗传和代谢病涉及化学药3条，生物药2条；感染涉及化学药2条，生物药1条，疫苗2条。 9月2日，锐正基因自主研发的针对转甲状腺素蛋白淀粉样变性（ATTR）的产品ART001近日美国IND申请通过。临床研究数据表明，受试者在用药4周后直至24周，高剂量组的外周TTR蛋白水平较基线平均下降超过90%。目前，所有受试者均已跟进36周或以上，药效依然保持稳定。ART001目前是中国唯一达到90%TTR敲降的体内基因编辑产品。 9月6日，GSK宣布了Nucala（Mepolizumab）的III期临床试验（MATINEE）积极结果。Nucala（美泊利单抗）是一种靶向成人慢性阻塞性肺病白细胞介素5（IL-5）的单克隆抗体。MATINEE在吸入维持治疗中加入Nucala达到了其主要终点，研究结果显示，与安慰剂相比，接受长达104周的患者中度/重度恶化的年化率降低具有统计学意义和临床意义，初步安全性结果与Nucala的已知安全性特征一致。全球新药研发进展详情（部分） 04 全球医药交易事件本次统计周期（2024.08.31-09.06）全球（含中国）医药交易时间共计26起，涉及药物权益转让、公司并购等多起交易事件。全球医药交易时间汇总表（部分）国内药物批准/研发动态 01 国内新药批准情况根据药渡数据统计分析，本次统计周期（2024.08.31-09.06）国内共有4个新药获NMPA批准上市。其中，NDA批准1个，BLA批准2个，新适应症批准1个。与上次统计周期相比，本次增加1个NMPA批准新药。 9月3日，菲洋生物宣布，地舒单抗注射液（恒盖®）获得国家药品监督管理局批准上市，用于治疗骨折高风险的男性和绝经后妇女的骨质疏松症。恒盖®与原研药普罗力®进行了严格的药学、非临床和临床的全面对比，结果表明，两者药学和非临床方面具有高度相似性；III期临床试验显示，主要疗效指标——受试者第12个月腰椎BMD较基线变化率在等效范围内，其他次要疗效指标和安全性指标也无统计学差异。 9月3日，NMPA批准了南京圣和药业的甲磺酸瑞厄替尼片，用于具有表皮生长因子受体（EGFR）外显子19缺失或外显子21（L858R）置换突变的局部晚期或转移性非小细胞肺癌（NSCLC）成人患者的一线治疗。III期临床研究结果显示，与吉非替尼组相比，本品显示出具有统计学和临床意义的PFS获益，瑞厄替尼组和吉非替尼组的中位PFS分别为19.3个月和9.8个月（HR=0.46，95% CI：0.33，0.65，p<0.0001）。国内新药批准情况（部分） 02 国内新药临床默示许可进展根据药渡数据统计分析，本次统计周期（2024.08.31-09.06）国内共有17个新药获临床默示许可，涉及24个受理号。其中，化学药8个，治疗用生物制品8个，预防用生物制品1个。与上次统计周期相比，本次减少22个临床默示许可获批受理号。本周国内新药临床默示许可进展（部分） 03 国内新药申报进展根据药渡数据统计分析，本次统计周期（2024.08.31-09.06）国内共有9个新药申报上市，涉及11个受理号。其中，化药4个，治疗用生物制品4个，预防用生物制品1个。与上个统计周期相比，本次减少6个新药申报上市受理号。国内新药申报上市情况根据药渡数据统计分析，本次统计周期（2024.08.31-09.06）国内共有36个新药申报临床，涉及53个受理号。其中，化学药17个，治疗用生物制品15个，预防用生物制品4个。与上次统计周期相比，本次减少7个临床申报受理号。国内新药临床申报情况（部分）根据药渡数据统计分析，本次统计周期（2024.08.31-09.06）国内共有5个药物获NMPA特殊资格认定。其中，化学药4个，生物药1个。与上次统计周期相比，本次增加4个获监管机构特殊资格认定的药物。 9月2日，NMPA药品审评中心官网最新公示，恒瑞医药注射用瑞康曲妥珠单抗拟纳入优先审评，用于既往接受过至少一种系统治疗的局部晚期或转移性HER2突变成人非小细胞肺癌患者的治疗。瑞康曲妥珠单抗由抗HER2抗体曲妥珠单抗、可裂解连接子及拓扑异构酶I抑制剂有效载荷SHR169265组合而成。临床研究结果显示全剂量组ORR为38.1%，DCR为90.5%，中位DOR为10.3个月，中位PFS为9.5个月；4.8mg/kg剂量组（RP2D, N=43）ORR为41.9%，DCR为95.3%，DOR为13.7个月，中位PFS为8.4个月。 9月6日，CDE官网公示，苏州赞荣医药申报的ZN-A-1041肠溶胶囊拟纳入突破性治疗品种，适应症为：ZN-A-1041联合卡培他滨和曲妥珠单抗用于既往接受过含曲妥珠单抗治疗进展的HER2阳性晚期脑转移乳腺癌患者。ZN-A-1041是一款口服小分子HER2靶向小分子抑制剂，具备高度血脑屏障通透性。研究结果显示，在19例至少两次肿瘤评估的脑转移乳腺癌患者中，ZN-1041联合卡培他滨和曲妥珠单抗的总ORR为78.9%，iORR为73.7%，DCR为100%。。国内监管机构特殊资格认定药物 04 国内新药研发进展根据药渡数据统计分析，本次统计周期（2024.08.31-09.06）国内新药临床研发状态更新共计2条，涉及肿瘤和心血管疾病共计2个领域。其中，化学药1条，生物药1条。与上次统计周期相比，本次减少1条国内新药临床研发状态更新。近日，恒瑞医药降脂创新药SHR-1918一项I期研究亮相2024 ESC年会。与安慰剂相比，SHR-1918在降低血清LDL-C和TG水平方面表现出显著效果，并具有剂量依赖性，300mg及以上剂量水平的LDL-C降低超过30%，持续64天以上，最高达49.1%；TG降低超过50%，持续85天以上，最高达82.8%。SHR-1918单次皮下注射在健康受试者中显示出良好的耐受性和药代动力学特性，且在给药后显示出良好的剂量-暴露-效应关系。SHR-1918作为一种潜在的降脂药物，能够有效降低LDL-C和TG水平。 9月5日，威尚生物医药宣布其新型EGFR抑制剂WSD0922完成首例受试者入组。WSD0922具有穿透血脑屏障潜力的第四代EGFR/EGFRvIII靶向抑制剂。7月8日，WSD0922获NMPA批准在中国开展I期桥接及II期扩展临床试验，用于经一线三代EGFR抑制剂治疗进展具C797S突变的晚期/转移性非小细胞肺癌。国内新药研发进展 05 国内新药研发领域政策法规动态本周暂无相关政策法规动态。 06 国内新药研发领域热点新闻赛诺菲BTK抑制剂III期成功，有效延缓多发性硬化症残疾进展 9月2日，赛诺菲发布公告称其BTK抑制剂Tolebrutinib在HERCULES III期研究中达到主要终点——与安慰剂相比，该药物可以有效延缓残疾进展。值得注意的是，这是首个也是唯一一个显示非复发继发性进行性多发性硬化症（MS）残疾积累减少的研究。关于MS MS是一种慢性、免疫介导的神经退行性疾病，随着时间的推移，会导致不可逆转的残疾。身体和认知障碍导致健康状况逐渐恶化，生活质量下降，影响患者的护理和预期寿命。目前，MS仍然不能治愈，残疾积累是MS中未得到满足的重要医疗需求。迄今为止，当前疗法……更多资讯，请阅读原文 9月3日，益诺思正式登陆科创板，恒瑞医药是其最大客户 9月3日，益诺思正式在科创板上市，发行总股份1.41亿股，每股19.06元。当下的国内CXO行业，沉浸在一片悲观的情绪中。内部环境中，行业正在经历结构性调整镇痛，无人能够幸免，各大参与者大打价格战，增量市场正逐步萎缩为存量市场；外部环境中，地缘政治举起“制裁”的大棒迎来来袭，这一棒威力值巨大，伤筋动骨在所难免。在这样的氛围中，益诺思的上市能否给这个动荡中的行业提振一点士气？更多资讯，请阅读原文 2024H1盘点：A股CXO市值蒸发2100亿元，仅一家幸免截至8月31日，A股5349家上市公司中已有5346家半年报披露完毕。其中，495家医药股中有250家实现了净利润同比增长，占比50.5%。从内外部环境来看，医药行业整体上已有触底反弹的迹象，但作为“卖水人”的CXO行业却仍在持续下探。A股市场所属同花顺行业包含医疗研发外包的29家上市公司中，28家股价下跌（以8月30日收盘价计，下同），仅诺泰生物一家得以幸免，占比96.6%，平均跌幅39.31%。 CXO的底在哪里，未来还值得期待吗？更多资讯，请阅读原文咨询、合作请联系作者小D有话说为方便读者阅读及保存，我们将周报原文整理成了PDF版本，如需获取全文，可点击最上方蓝字，在药渡Daily公众号后台回复“0913创新药周报”，即可下载。

孤儿药上市批准快速通道

2024-09-04

·GlobeNewswire-Health Care

Actimed Therapeutics Announces US FDA Grant of Orphan Drug Designation to S-oxprenolol (ACM-002) for the Treatment of Amyotrophic Lateral Sclerosis (ALS)

London, UK – 4th September 2024. Actimed Therapeutics Ltd (“Actimed”), a UK based clinical stage specialty pharmaceutical company focused on bringing innovation to the treatment of cancer cachexia and other muscle wasting disorders, announces that the US Food and Drug Administration (FDA) has granted Orphan Drug Designation to S-oxprenolol (ACM-002) for the treatment of amyotrophic lateral sclerosis (ALS). ALS (also known as Lou Gehrig’s disease) is a progressive, fatal neuromuscular disease that affects nerve cells in the brain and spinal cord, eventually leading to a loss of muscle control and paralysis. ALS prevents motor neurons sending impulses from the brain and spinal cord to the muscles, causing muscle atrophy and weakness and has a mean survival of 3.5 years. Voluntary muscle action is progressively lost and in late-stage ALS patients may have difficulty communicating, swallowing, moving, and breathing. There is currently no cure for ALS. Cachexia, a complex wasting disease, may occur in the early stages of ALS and has a significant impact on quality of life, proving terminal in some patients. In pre-clinical ALS models, S-oxprenolol has demonstrated significant benefits including slowing disease progression, improvement in survival, attenuation of muscle loss, motor neuron protection, reduction in loss of body mass and improvements in lean body mass1. Robin Bhattacherjee, Chief Executive Officer of Actimed Therapeutics commented “We are pleased to receive Orphan Drug Designation for S-oxprenolol in ALS, where loss of body mass and muscle wasting can have a significant impact on survival. ALS is a devastating orphan disease of high, unmet medical need and the early non-clinical data we have generated for S-oxprenolol in this indication suggest that it could have a potential role in meeting some of the important needs of this under-served patient population”. FDA Orphan Drug Designation is granted to investigational therapies which are intended for the safe and effective treatment, diagnosis or prevention of rare diseases or conditions that affect fewer than 200,000 people in the United States. Orphan Drug Designation provides several benefits to drug developers, including certain development cost benefits in the US, increased FDA interaction and eligibility for seven-year market exclusivity following approval. *** About Actimed Therapeutics Actimed Therapeutics is a clinical stage specialty pharmaceutical company focused on bringing innovation to the treatment of muscle wasting disorders to transform the care of an underserved and vulnerable patient population. The lead area of focus for Actimed is specifically in cachexia. Cachexia is a wasting disease that is associated with cancer and other serious chronic illnesses and with significant morbidity and mortality. A significant number of cancer patients suffer from cachexia2 and it is estimated that cachexia is responsible for up to 20% of all cancer deaths3. A recent meta-analysis demonstrated that cachexia was associated with an 82% higher relative risk of mortality in patients with NSCLC versus no cachexia4. Despite its prevalence and devastating clinical effects, there is no globally approved drug for the treatment or prevention of cancer-related cachexia. The lead product of Actimed, S-pindolol benzoate (ACM-001.1) targets multiple pathways that drive cachexia and has generated promising proof of concept Phase 2a clinical data in cachexia patients. Actimed is currently preparing for further clinical studies in cancer cachexia having received an Investigational New Drug (IND) approval from FDA for this programme in August 2023. Actimed also owns the global rights to its second asset, S-oxprenolol, which is being developed by the Company for the muscle wasting seen in amyotrophic lateral sclerosis (ALS) where loss of body mass and muscle wasting may impact survival5. Actimed has licensed the global rights to develop and commercialise S-oxprenolol for cancer cachexia and any other indications outside of ALS to US company Faraday Pharmaceuticals. FOR MORE INFORMATIONActimed Therapeuticswww.actimedtherapeutics.com MEDiSTRAVA ConsultingFrazer Hall, Erica HollingsworthTel: +44 (0)203 928 6900Email: actimed@medistrava.com ___________________________ 1Suzuki et al, JCSM 2018; 9, 183-212. (Poster 5-17, page 200)2 Anker M et al., J. Cachexia, Sarcopenia and Muscle; 2019: 10: 22 – 243 Argilés JM et al, Nat Rev Cancer 2014; 14:754-624 Bonomi P. et al. The mortality burden of cachexia in patients with non-small-cell lung cancer: A meta-analysis; International Conference of Sarcopenia, Cachexia and Wasting Disorders, June 17 – 18 2023, Stockholm, abstract 2-18, page 1395Wolf J et al., PMID 28184974 DOI: 10.1007/s00115-117-0293

临床2期孤儿药

2024-09-04

·Pharmaceutical Technology

Actimed’s ALS candidate wins FDA orphan drug designation

ALS prevents motor neurons from sending impulses from the brain and spinal cord to the muscles, causing muscle atrophy and weakness. Image credit: Shutterstock / CC7. The US Food and Drug Administration (FDA) has granted an orphan drug designation to Actimed Therapeutics’ S-oxprenolol (ACM-002) for the treatment of amyotrophic lateral sclerosis (ALS). The UK-based pharma company will now be in line for tax credits for US-based clinical trials, and if the therapy is approved, the potential for seven years of market exclusivity in the designated indication, as per a 4 September press release. Actimed says S-oxprenolol shares “a similar pharmacology” to S-pindolol, which is an anabolic/catabolic transforming agent. S-pindolol benzoate, Actimed’s lead product, is being investigated for the treatment of the metabolic weight loss syndrome called cachexia. With S-oxprenolol, Actimed is targeting S-pindolol’s mechanistic approach in the wasting syndrome to address the loss of body mass and muscle wasting seen in ALS. ALS is the most common form of motor neuron disease. Muscle wasting is seen in patients as motor neuron degeneration means muscles no longer receive electrical signals. See Also: ESC 2024: Beta blocker treatment paradigm shifts for myocardial infarction Novavax wins FDA emergency approval for updated Covid-19 vaccine There are currently six FDA-approved therapies for ALS, though the agency has developed a five-year plan to accelerate the development of more treatments and improve medicine access. There have been a few recent setbacks in the space, including Amylyx Pharmaceutical’s Phase III failure and Ionis/Biogen’s decision to discontinue the development of their ALS candidate. In preclinical ALS models, S-oxprenolol has demonstrated an ability to attenuate muscle loss, improve lean body mass, and reduce the loss of overall body mass, amongst other benefits. Oxprenolol is a beta blocker usually used for the treatment of heart conditions such as angina and high blood pressure. While Actimed has not disclosed the mechanism of action in ALS, the related compound S-pindolol increases anabolism and muscle by partial beta-2 receptor agonism. Actimed is currently conducting trials for S-pindolol in cancer cachexia, a sub-type of the syndrome found in cancer patients. The compound has demonstrated positive proof of concept data in a Phase IIa study, with further clinical trials planned according to the company. Actimed has yet not unveiled details of a clinical programme for S-oxprenolol. Nonetheless, the company has already licensed the drug’s global rights for cancer cachexia and non-ALS indications to US company Faraday Pharmaceuticals. The deal, signed in 2021, included an upfront payment of $550,000 and $126.2m in milestone payments. Actimed’s CEO Robin Bhattacherjee said: “The early non-clinical data we have generated for S-oxprenolol in this indication suggest that it could have a potential role in meeting some of the important needs of this under-served patient population.”