Datopotamab Deruxtecan

The pairing of two Bristol Myers Squibb immunotherapies is now permitted for the first-line treatment of two types of gastrointestinal cancers, after regulatory decisions handed out this past week that convert the accelerated approval status of the drug combination to full FDA approval in both indications. The drugs, Opdivo and Yervoy, belong to the class of medicines called checkpoint inhibitors. On April 8, the FDA approved use of this drug combination for adults and children age 12 and older whose colorectal cancer has metastasized or cannot be removed by surgery. The cancer must also be microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), references to biomarkers that indicate the stability of DNA in a tumor. The regulatory submission was based on the results of an open-label Phase 3 test that compared the Opdivo/Yervoy combination to either Opdivo alone or chemotherapy. Results showed the immunotherapy combination led to a 38% reduction in the risk of disease progression or death compared to Opdivo monotherapy, and by 79% compared to chemo, both in the first-line setting. The study is ongoing to assess secondary measures, including overall survival. BMS said it will continue working with study investigators to present these data and longer-term follow-up results in the future. Sponsored Post Changes in Nurse Staffing Answer Clinician Demands The ongoing nursing shortage facilitates high turnover rates since nurses know they won’t have difficulties finding new jobs. In order to retain and attract staff, it’s in a facility’s best interest to understand what nurses want. By Tomasz Rezik On April 11, the FDA approved the combination of Opdivo and Yervoy for treating advanced cases of hepatocellular carcinoma. In the pivotal test in this indication, the drug combination led to median overall survival of 23.7 months. The comparator arm, in which patients received standard of care drugs sorafenib or levantinib, median overall survival was 20.6 months. At three years, the drug combination showed an overall survival rate of 38% versus 24% in the comparator arm. FDA approval of Opdivo plus Yervoy in hepatocellular carcinoma follows the European Commission’s early March approval of the drug combination in this indication. There’s plenty of news on the regulatory front. Here’s a recap of other recent highlights: New and Expanded Regulatory Approvals —Argenx drug Vyvgart Hytrulo received an additional approval for dosing of the product via a prefilled syringe. The drug, supplied in vials, previously received FDA approvals for the autoimmune conditions chronic inflammatory demyelinating polyneuropathy and generalized myasthenia gravis. Analysts say prefilled syringes bring patients a more convenient dosing option while giving Argenx the opportunity to get more market share by penetrating into earlier lines of therapy. Sponsored Post Understanding EGPA: The Role of Eosinophils and Advancements in Treatment Options FASENRA® (benralizumab) injection, for subcutaneous use, 30 mg is indicated for the treatment of adult patients with eosinophilic granulomatosis with polyangiitis (EGPA). FASENRA provides a treatment option for HCPs to consider when managing this challenging disease. By FASENRA, Sponsored Content —Amgen’s Uplizna expanded its label to include the treatment of immunoglobulin G4-related disease (IgG4-RD), an immune-mediated inflammatory disorder that can affect multiple organs. The regulatory decision makes the intravenously infused antibody the first FDA-approved treatment for this rare and chronic disease. Uplizna was first approved in 2020 as a treatment for neuromyelitis optica spectrum disorder. —Bayer’s Viktrakvi now has full FDA approval for the treatment of NTRK gene fusion-positive solid tumors in adults and children without a known acquired resistance mutation. The drug received accelerated approval in this indication in 2018. —AstraZeneca and Daiichi Sankyo welcomed European Union approval of Datroway as a treatment for metastatic breast cancer that is HR positive and HER2 negative. Datroway received FDA approval in the same indication in January. The drug is an antibody drug conjugate designed to target the cancer protein TROP2. —Novartis drug atrasentan, brand name Vanrafia, was awarded accelerated approval as a new treatment for the kidney disorder immunoglobulin A nephropathy (IgAN). The drug is an oral small molecule designed to block the endothelin A receptor. It’s one of two IgAN nephropathy drugs that came via the $3.2 billion acquisition of Chinook Therapeutics in 2023. Novartis’s internal IgAN research yielded the complement inhibitor Fabhalta, which received accelerated approval in this indication last summer. —Speaking of Fabhalta, that Novartis drug expanded its label to include C3 glomerulopathy, making the twice-daily pill the first approved treatment for this rare kidney disorder. Fabhalta is a small molecule designed to block the complement protein C3. It was first approved in 2023 as a treatment for the rare blood disorder paroxysmal nocturnal hemoglobinuria. —Sanofi received FDA approval for fitusiran, brand name Qfitlia, as a treatment for both hemophilia A and B. The drug leverages RNA interference to lower levels of AT, a protein that inhibits blood clotting. The approval covers the treatment of adults and children age 12 and older with or without inhibitors, which are antibodies that can develop in hemophilia patients, making it more difficult to control bleeding. By contrast, new Pfizer drug Hympavzi is approved only for hemophilia A and B patients without inhibitors while Sanofi’s Alhemo is approved only for hemophilia A and B patients with inhibitors. —Blockbuster AstraZeneca cancer immunotherapy Imfinzi landed European Union approval for the treatment of limited-stage small cell lung cancer. This new approval is based on Phase 3 results showing a 27% reduction in the risk of death compared to a placebo. The FDA approved Imfinzi for this indication last December. —Imfinzi also added perioperative treatment of muscle invasive bladder cancer to its list of FDA-approved indications. The newest FDA nod covers use of the drug in combination with chemotherapy before surgery to remove the bladder, followed by Imfinzi as an adjuvant monotherapy. In the pivotal study supporting this new indication, results showed a 32% reduction in the risk of cancer recurrence and a 25% reduction in the risk of death compared to neoadjuvant chemotherapy alone. —The European Commission approved Pfizer vaccine Abrysvo for protection against respiratory syncytial virus (RSV). The regulatory decision expands the vaccine’s approval to adults ages 18 to 59. European regulators initially approved the vaccine in 2023 for preventing lower respiratory tract disease in adults age 60 and older. Abrysvo won FDA approval the same year. —The FDA expanded approval of Novartis’s Pluvicto to include use as an earlier line of treatment — after anti-androgen drugs and before chemotherapy — for PSMA-positive metastatic castration-resistant prostate cancer (mCRPC). Pluvicto was initially approved in 2022 for PSMA-positive mCRPC that has already been treated with an anti-androgen drug and chemotherapy. Novartis said this expansion is important because about half of patients do not live long enough to receive a second-line treatment. —Exelixis cancer drug Cabometyx expanded its FDA-approved uses to advanced cases of pancreatic neuroendocrine tumors (pNET) and extra-pancreatic neuroendocrine tumors (epNET). The approval covers adults and children age 12 and older. Cabometyx is a small molecule designed to block enzymes that support cancer growth. The drug was first approved in 2016 for advanced renal cell carcinoma. —GSK landed FDA approval for Blujepa, an oral antibiotic developed to treat uncomplicated urinary tract infections. While drugs are already available for these infections, they can become resistant to treatment. Blujepa is designed to block two enzyme targets key to bacterial DNA replication, an approach intended to lower the potential for drug resistance. —The European Commission approved Capvaxive, a pneumococcal vaccine developed by Merck to protect against the 21 Streptococcus pneumoniae serotypes that lead to the majority of cases of invasive pneumococcal disease including eight that are not covered by any other available pneumococcal vaccine. The European regulatory decision covers adults age 18 and older. Capvaxive received FDA approval last July. —Alynlam Pharmaceuticals drug Amvuttra received FDA approval for treating cardiomyopathy caused by transthyretin amyloidosis (ATTR). The RNA interference drug was first approved in 2022 for the treatment of polyneuropathy caused by ATTR. In the cardiomyopathy indication, it will compete with Pfizer’s Vyndaqel and Vyndamax, which are established as the standard of care, as well as Attruby, a BridgeBio Pharma drug that received FDA approval last fall. —Bristol Myers Squibb’s Breyanzi received European Commission approval for relapsed or refractory follicular lymphoma. The CAR T-therapy received accelerated FDA approval in this indication last May. —Geron Corporation’s Rytelo received European Commission approval for the treatment of transfusion-dependent anemia caused by lower-risk myelodysplastic syndrome, a progressive type of blood cancer. The intravenously infused drug is the first telomerase inhibitor to reach the market. Rytelo landed FDA approval last June. —Neffy, an epinephrine nasal spray that ARS Pharmaceuticals developed to treat allergic reactions to insect bites, medications, and food, expanded its FDA approval to include patients weighing 15 to 30 kilograms (about 33 to 60 pounds). The product’s initial approval last year covered its use in patients weighing 30 kg or more. —Roche subsidiary Genentech received FDA approval for tenecteplase, brand name TNKase, as a treatment for acute ischemic stroke in adults. Genentech said TNKase is the first stroke medicine approved by the FDA in nearly 30 years. It’s the second approved indication for the clot-busting drug. The FDA approved it in 2000 for treating acute myocardial infarction. —A Neurotech Pharmaceuticals cell and gene therapy administered via a surgical implant received FDA approval for the treatment of macular telangectasia type 2. The therapy, brand name Encelto, is the first approved treatment for this rare vision-loss disorder. Regulatory Setbacks —The FDA missed the April 1 regulatory decision target date for Novavax’s Covid-19 vaccine. Politico reported the holdup was due to the intervention of Sara Brenner, the FDA’s principal deputy commissioner, who asked for more data. Novavax said it has responded to all of the FDA’s information requests and believes the application is ready for approval based on the submitted Phase 3 data. Novavax’s protein-based vaccine initially received FDA emergency use authorization in 2022, a status that it retained under amended authorizations in 2023 and last year, both times for new formulas that covered the prevalent variants at the time. Full FDA approval would put the vaccine on par with the approved messenger RNA vaccines marketed by Pfizer and Moderna. Novavax’s Covid-19 vaccine will be co-commercialized with Sanofi under a partnership announced last year. —Roche paused European clinical tests of the Duchenne muscular dystrophy gene therapy Elevidys, the pharmaceutical giant said in a letter to the World Duchenne Organization. The move follows Sarepta Therapeutics’ recent report of a liver failure-associated patient death. Roche said the European Medicines Agency asked for a clinical hold on four studies until the inquiry into the cause of death is complete. Under a 2019 deal with Sarepta, Roche holds rights to Elevidys outside of the U.S. —For the second time, the FDA has rejected Aldeyra Therapeutics drug reproxalap as a treatment for dry eye disease. The agency turned down an application for the drug in 2023. According to Aldeyra, the FDA’s latest complete response letter said the new drug application failed to demonstrate efficacy. The regulator asked the company to run at least one more clinical trial. Among the concerns raised by the FDA is differences in baseline scores, which may have affected interpretation of trial results. Aldeyra said results from two ongoing studies are expected later in the current quarter, potentially paving the way for a mid-year resubmission of the application. —The European Medicines Agency refused marketing authorization for Eli Lilly Alzheimer’s disease drug Kisunla. Safety was the main reason cited, particularly the brain inflammation and bleeding that is a known complication risk associated with all drugs in the same class of Alzheimer’s medicines. The agency said the drug’s benefits were not enough to outweigh the potentially fatal safety risks. The FDA approved Kisunla last July. —In other Alzheimer’s drug news, Eisai again failed to persuade Australia’s drugs regulator to register Leqembi. The pharma company had asked the Therapeutics Goods Administration (TGA) to reconsider its October 2024 decision to not register the drug in Australia. Eisai’s request for reconsideration covered a narrower indication, but Eisai said the TGA did not agree that safety has been established for these patients.

昨天分享了一些肺癌靶向用药中，三代EGFR-TKI药物的相关数据（这个赛道，能容下这么多新药吗？），今天补充一下其他靶向用药的国内市场销售数据。1、EGFR突变最常见突变，占比最大，用药最多。一代、二代TKI基本被淘汰。全球市场基本被淘汰。国内市场吉非替尼、厄洛替尼国采后，价格大幅下降，市场销售大幅下降，基本被淘汰。国产新药埃克替尼凭借独家优势，以及贝达的推广能力，仍有较大市场规模。但面临更多的国产三代TKI冲击。三代TKI是核心一线方案。三代药物可以克服T790M耐药，能更好的穿透血脑屏障，对合并脑转移患者更有优势。国内已上市1个进口，6个国产三代TKI。奥希替尼最早上市，获批适应症最多，证据最充分。国产三代新药结构、适应症、疗效指标相似，竞争激烈。三代TKI国内医院市场年销售额约100亿元，原研进口的奥希替尼销售额稳定。早先获批的阿美替尼、伏美替尼销售大幅增长，份额不断增加。来源：摩熵医药未来的新一线方案。最有潜力的是强生的埃万妥单抗联合兰泽替尼。在全球多中心III期MARIPOSA临床中，一线方案头对头击败奥希替。埃万妥单抗显著延长患者的 PFS（23.7vs16.6 个月，HR=0.70）。2024年8月该疗法已获FDA批准，未来可能改写一线治疗方案。埃万妥单抗皮下注射剂型，显示出更好的疗效和安全性。PALOMA-3试验数据显示，皮下注射剂型组在mDOR（11.2vs8.3），mPFS（6.1vs4.3），mOS（HR=0.62）等终点中均占据优势，相关不良反应发生率更低（13%vs66%）。浙江通源的三代氘代 EGFR-TKI TY-9591是也开展头对头奥希替尼的大型临床研究。治疗三代EGFR-TKI耐药，是新药的发力方向。重点药物类型包括：抗体耦联药物（ADC)、 PD-1/PD-L1、MET靶向药。ADC药物：科伦博泰的药物SKB264（TROP2 ADC），百利天恒的BL-B01D1（HER3 ADC）。第一三共/阿斯利康德达博妥单抗（Dato-DXd）用于EGFR突变NSCLC患者（EGFR-TKI和铂类化疗后进展），2025年1月获FDA优先审评资格。PD-1/PD-L1：康方的PD-1/VEGF 双抗依沃西单抗，2024年5月在国内获批联合化疗治疗经 EGFR TKI（包括一二代）治疗后进展的 nsq-NSCLC患者。信迪利单抗(PD-1)联合贝伐珠单抗+含铂化疗，用于三代TKI治疗后患者适应症获批。MET靶向药：埃万妥单抗联合化疗或靶向药物，已在美国、欧盟获批用于奥希替尼耐药患者，并已在中国提交进口上市申请。2、ALK重排NSCLC中占比3-7%，钻石突变，靶向治疗效果好，治疗后长期生存率高。ALK抑制剂历经三次迭代。一代：克唑替尼。最早上市，从2020年开始，销售额就大幅下降。复星万邦首仿已经获批。二代：阿来替尼、布格替尼、恩沙替尼、依奉阿克、伊鲁阿克。阿来替尼上市多年，国内销售表现强劲，年销18亿元。齐鲁的伊鲁阿克，在一线和二线方案的临床数据表现，最为出色。但二代产品的同质化竞争依然严重。正大天晴的依奉阿克也是强劲对手。三代：洛拉替尼。由辉瑞研发，全球首个获批的第三代ALK。与前两代相比，洛拉替尼具备更强的血脑屏障穿透能力，对颅内肿瘤也有较好的控制效果，在基线伴随脑转移的患者中更具优势。洛拉替尼对一代、二代 ALK 抑制剂耐药的患者仍然有效， 目前临床上常使用二代TK 耐药后再序贯三代TKI的“2+3 模式”。国内上市时间不长，但增长很快，去年半年销售额超过2亿。3、METc-MET 抑制剂有望用于多种肿瘤的治疗。国内已获批5个药品：和黄的赛沃替尼、中美冠科的伯瑞替尼、上海海和的谷美替尼、诺华的卡马替尼、默克的特泊替尼。首发适应症均为外显子14跳变的NSCLC，各产品的临床数据结果差距相当。和黄的赛沃替尼具有先发优势，年销超2亿，又拓展了EGFR TKI耐药适应症，潜力较大。4、KRAS最常见的突变基因之一，一直是肿瘤新药热门方向，其中，G12C是常见类型，但已获批的药物较少。全球仅有3款，BMS的阿达格拉西、安进的索托拉西布还未获批进口。信达/劲方的氟泽雷塞2024年8月抢到国内首个获批，正大天晴的格索雷塞第二家上市，加思科的格来雷塞上市申请还在审批中。还没有销售数据。但此类药物单药效果并不明显，BMS和安进的产品卖的都不好。各企业的临床开发路线，选择抱大腿：和PD1等其他药物联用。5、ROS1占比较少，药物不多，主要都是进口产品。再鼎与BMS联合开发的瑞普替尼，信达的他雷替尼，临床结果数据略有优势。暂无销售数据。6、HER2重点是HER2 ADC，第一三共的德曲妥珠单抗在2022年获FDA批准，拓展经治HER2突变的转移性NSCLC适应症， 肺癌领域首个获批HER2靶向治疗方案，完成概念验证。这个适应症在国内刚刚获批。国产恒瑞的SHR-A1811进展最快，2024年9月已提交上市申请。其他有多个企业参与，但进度较慢。7、BRAF药物很少，全球已上市两款，分别是诺华的达拉非尼，2019年就获批进口，国内医院市场销售额约3亿元。辉瑞的恩考芬尼还未进口。这两个产品都需要和其他药物联用。国内企业布局较少。8、RET全球仅两个产品，分布是基石药业引进的普拉替尼，信达引进的塞普替尼，国内卖的不多。9、NTRK突变发生率很低，只有0.23%。NTRK 抑制剂多为多靶点抑制剂，共四个产品获批上市：拉罗替尼、恩曲替尼、瑞普替尼、他雷替尼。除罗氏的恩曲替尼外，其他产品上市时间不长，还没有销售数据。用摩熵药筛小程序，快速查询产品申报进展！