Atrasentan

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.

关注并星标CPHI制药在线近日，免疫球蛋白A（IgA）肾病领域好消息不断：3月31日，大冢制药宣布已向FDA提交Sibeprenlimab治疗免疫球蛋白A（IgA）肾病的生物制品许可申请（BLA）；4月3日，诺华阿曲生坦（atrasentan，Vanrafia）被FDA加速批准，用于降低有疾病进展风险的原发性免IgA肾病成人患者的蛋白尿。关于SibeprenlimabSibeprenlimab（VIS649） 是一款抗增殖诱导配体（APRIL）单抗，通过结合和中和APRIL，减少IgA和致病性半乳糖缺乏型 IgA1 (Gd-IgA1)的数量。通过减少 Gd-IgA1的产生，Sibeprenlimab 可能有助于减缓肾脏损伤和向终末期肾病(ESKD) 进展。2024年2月，该药被FDA授予治疗IgA肾病的突破性疗法认定。《新英格兰医学杂志》（NEJM）上发表的Sibeprenlimab治疗IgA肾病的2期临床试验结果显示：与安慰剂治疗相比，IgA肾病患者接受为期12个月的sibeprenlimab治疗后，蛋白尿状况显著减少，eGFR下降延缓。此次Sibeprenlimab递交的BLA是基于2期临床试验ENVISION和3期临床试验VISIONARY的积极结果。VISIONARY是一项多中心、随机、双盲、安慰剂对照试验，在约530名（同类中规模最大的）IgA肾病成年患者中开展，旨在评估每四周皮下注射400 mg的Sibeprenlimab的疗效和安全性。2024年10月，大冢制药宣布VISIONARY试验取得积极中期结果。由独立数据监测委员会进行的预定中期分析显示，VISIONARY研究达到了主要终点--与安慰剂相比，Sibeprenlimab在治疗9个月后显著且具有临床意义地降低了24小时尿蛋白/肌酐比值。而且，Sibeprenlimab的安全性与此前报告的数据一致。值得一提的是，Sibeprenlimab最初由Visterra公司开发，2018年大冢制药通过收购Visterra将其纳入囊中。Sibeprenlimab的申请上市距离其造福IgA肾病患者又近一步。关于阿曲生坦阿曲生坦是一种选择性内皮素A受体拮抗剂（ERA），通过阻断内皮素-1（ET-1）与内皮素A受体的结合，减少肾脏损伤，延缓疾病进展。而ET-1是一种强效内源性血管收缩物质，与内皮素A受体结合后，会诱发广泛的病理生理学效应，包括足细胞损伤、蛋白尿产生、系膜细胞损伤、增殖和纤维化等。2023年6月，诺华通过收购Chinook公司，将包括阿曲生坦和APRI单抗zigakibart两款IgA肾病药物纳入囊中。此次阿曲生坦获批是基于3期临床试验ALIGN的积极结果：36周时，与安慰剂+支持治疗相比，阿曲生坦组患者蛋白尿减少36.1%。值得一提的是，阿曲生坦是首个获批用于减少原发性IgA肾病蛋白尿的选择性ETA拮抗剂。       IgA肾病治疗进展IgA肾病是最为常见的原发性肾小球疾病，是导致进行性肾脏疾病和肾衰竭的主要原因之一。该病是一种进展性自身免疫性慢性肾病，特点是含IgA的免疫复合物在肾小球系膜区沉积。患者临床表现多样，如患者可能出现复发性血尿、蛋白尿以及呼吸道或胃肠道感染。目前，IgA肾病的病理机制还未完全明确。但目前被广泛接受的"多重打击假说"认为IgA肾病是多种机制共同导致的。总的来说，该假说有4个环节：在遗传易感性、外界刺激以及细胞因子如BAFF和APRIL的作用下B细胞产生过量半乳糖缺乏的IgA（Gd-IgA）；Gd-IgA1 作为自身抗原诱发自身抗体的产生（抗糖抗体）；Gd-IgA和抗糖基抗体形成循环免疫复合物；免疫复合物沉积在肾小球系膜区域引起损伤。IgA肾病患者人群庞大。据弗若斯特沙利文报告，全球IgA肾病患者人数已由2016年的887.64万人增加至2020年的926.69万人，预计2025年将增加到973.06万人，2030年达到1016.52万人。鉴于庞大的IgA肾病患者体量，越来越多的药企开始布局该领域，并取得不错进展。据不完全统计，近年来全球监管机构已批准多款IgA肾病新药，如Nefecon（每日一次）、Sparsentan（每日一次）、伊普可泮（每日两次）。其中Nefecon是一种布地奈德的缓释制剂，通过覆以肠溶包衣，使其可以完整无损地到达回肠，靶向作用于回肠末端的黏膜 B 细胞（包括派尔集合淋巴结），从而减少诱发 IgA 肾病的半乳糖缺陷的 IgA1 抗体（ Gd-IgA1 ）产生。2021年12月，该药被FDA加速批准用于降低有疾病快速进展风险(通常为尿蛋白与肌酐之比(UPCR) ≥1.5g/g)的成人原发性IgA肾病患者的蛋白尿。2023年12月，该药获FDA完全批准，成为全球首个且唯一获得FDA完全批准用于治疗有进展风险的IgA肾病的药物，减少肾功能减退，且无基线蛋白尿水平限制。Sparsentan是一款双重内皮素血管紧张素受体拮抗剂，靶向阻断内皮素A受体和血管紧张素II亚型1受体通路，有利于保护肾小球足细胞，防止肾小球硬化和系膜细胞增生以减少蛋白尿。2023年2月，该药被FDA批准用于具有疾病快速进展风险，且尿蛋白与肌酐比值（UPCR）≥1.5 g·g－1的原发性IgAN成人患者。伊普可泮是一款口服、强效、选择性、小分子补体途径因子B抑制剂，能高效抑制补体替代通路中因子B，2024年8月被FDA批准用于降低成人IgA肾病患者的蛋白尿水平。END2025金笔奖征文活动开启，来投稿吧！领取CPHI & PMEC China 2025展会门票智药研习社直播预告来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com▼更多制药资讯，请关注CPHI制药在线▼点击阅读原文，进入智药研习社~