Belzutifan

编者按：透明细胞肾细胞癌（ccRCC）普遍与VHL通路失调相关，这会导致HIF-2α过度表达并上调多种致癌通路。而针对HIF-2α的治疗策略，如贝组替凡等药物为这类VHL患者，甚至肾癌患者带来了新的希望。在今年ASCO GU年会上，肿瘤瞭望-泌尿时讯特邀北京大学第一医院龚侃教授对话MD安德森癌症中心VHL临床中心主任Eric Jonasch教授，共同解读贝组替凡获益人群及不良反应管理，以及未来应用前景。 01 《肿瘤瞭望-泌尿时讯》 贝组替凡已经在2021年获FDA批准治疗VHL病，能否分享一下您的临床实践经验？您在临床实践中，主要在什么疾病阶段（治疗时机）选择贝组替凡？以及对贫血、疲劳等常见不良事件的管理？ Eric Jonasch 教授 MD安德森癌症中心VHL临床中心主任 对于患有VHL病的患者，我们会观察患者最终是否有可能出现多种威胁性病变，从而决定是否需要干预，这因素包括：肾脏肿瘤≥3 cm、可能出现中枢神经系统血管母细胞瘤、胰腺神经内分泌肿瘤等。一般而言，如果患者仅存在一个病变（例如肾脏的一个部位），通过消融或手术干预即可使患者正常生存，而不需要额外干预，此时我们不会为他们推荐贝组替凡。而对于存在多个病变的患者（可能会影响患者生存，并导致患者多次手术），我们通常会推荐贝组替凡。 使用贝组替凡时，我们也会随访并跟踪分析患者的毒副作用。研究发现，最常见的不良反应（AE）是贫血，贫血原因是HIF-2α通过结合促红细胞生成素（EPO）基因中控制其氧依赖性转录的特异性调节元件来介导红细胞生成素的生成；而使用贝组替凡会抑制EPO的转录，因而会造成贫血。在我的实践中，我们通常会使用促红细胞生成素刺激剂来提高血红蛋白水平。 其次常见的AE是缺氧，在年轻的VHL病患者中，我们很少见到这种症状。但在老年VHL病患者和晚期肾癌患者中，确实会出现这种副作用。我们会跟踪随访，并要求每位患者通过血氧仪分析期血氧水平：如果血氧水平低于90%，会暂停用药；等到血氧水平超过92%后，再降低使用剂量。 第三个副作用是疲劳，我们通常通过减少剂量来进行改善。 That looks like they're beginning to potentially cause neurological problems or pancreatic neuroendocrine tumors that are approaching three centimeters in size. And in general, if we have a patient that has only one lesion, for example, one spot in the kidney, where an intervention with an ablation or a surgery would allow them to then have a long period of time where they would not need additional interventions, we would not offer Belzutifan to them. We typically are offering Belzutifan to patients who have multiple lesions that look like they're going to cause problems and would result in them having multiple surgeries. So we start Belzutifan on those individuals, and we then follow them for the toxicities. The major toxicities include anemia, and the reason they get anemia is because erythropoietin (EPO) is a HIF-2α client gene. So we're basically knocking down transcription of EPO. We, in my practice, typically are using erythropoietin-stimulating agents to bring up the hemoglobin levels. The second major toxicity is hypoxia, which we don’t see very often in patients with VHL disease when they’re younger, but we do see it in older VHL disease patients and also in patients with advanced kidney cancer. There, what we do is we will follow. We ask every patient to get a pulse oximeter, we have them watch their oxygen levels. If it goes below 90%, we have them hold the drug, we wait till it goes above 92%, and then have them lower the dose. The third side effect is fatigue, and that is something that we manage usually with dose reduction. 上下滑动查看 龚侃 教授 北京大学第一医院 为什么嗜铬细胞瘤和副神经节瘤（PPGL）患者使用贝组替凡的疗效不佳？ Eric Jonasch 教授 MD安德森癌症中心VHL临床中心主任 我们也观察到了这种现象，但我们对PPGL的诊治经验较少，暂时还未进行深入研究。 龚侃 教授 北京大学第一医院 在中国的VHL患者数据中，贝组替凡治疗PPGL患者的疗效并不明显；但在VHL综合征肾癌患者中，贝组替凡的疗效显著。 Eric Jonasch 教授 MD安德森癌症中心VHL临床中心主任 那么这些PPGL患者均与VHL相关吗？这个现象很有趣。 龚侃 教授 北京大学第一医院 是的，因此我们团队收集了PPGL相关数据，并试图分析其中的原因。我们想了解为什么贝组替凡在PPGL患者中表现不佳。 Eric Jonasch 教授 MD安德森癌症中心VHL临床中心主任 可能还存在您所提及的VHL以及其他突变，这些突变共同导致了该疾病的生物学特性。这非常有趣，值得进一步探索。 02 《肿瘤瞭望-泌尿时讯》 贝组替凡用于晚期透明细胞肾细胞癌（ccRCC）治疗也取得了突破性进展，例如2024年发表于NEJM的III期临床研究。两位对贝组替凡未来的应用前景有怎样的展望？ 龚侃 教授 北京大学第一医院 这一问题具有重要意义。在晚期肾癌治疗领域，当前已有众多药物可供选择，无论是欧洲泌尿外科协会（EAU）还是美国泌尿外科协会（AUA）发布的指南，针对晚期肾癌的一线、二线乃至后线治疗方案，均已被广泛熟知与应用。对于肾透明细胞癌及非透明细胞癌的治疗，临床实践中也积累了丰富的参考依据。 然而，就目前所获取的数据而言，贝组替凡在肾透明细胞癌，尤其是晚期肾透明细胞癌的治疗中，展现出了令人振奋的疗效。因此，我个人认为其将在晚期肾癌治疗领域开启一个全新的纪元。现阶段指南或将其列为二线治疗方案，但随着临床经验的不断积累以及更多数据的证实，贝组替凡在晚期肾癌治疗中的地位与作用将会日益凸显。 从此次LITESPARK-015研究的中国数据来看，贝组替凡的表现令人惊喜。在安全性方面，其导致的贫血、乏力、缺氧等不良反应总体处于可控范围，安全性良好。在治疗过程中，我们需要组建多学科诊疗团队（MDT），联合内科医生共同为患者提供全程规范的治疗。故而，我坚信贝组替凡有望成为未来晚期肾癌治疗的有力武器。 至于联合免疫治疗是否将成为未来的新方向，贝组替凡与免疫治疗联合能否带来更佳疗效，仍有待进一步探索与验证。因此，我与Eric Jonasch教授就此进行了深入交流，双方机构计划进一步开展合作研究，期望通过共同努力为该领域带来新的突破与惊喜。 Eric Jonasch 教授 MD安德森癌症中心VHL临床中心主任 贝组替凡获得FDA批准用于晚期肾细胞癌（RCC）治疗，这一进展对患者而言意义非凡。LITESPARK-005研究入组了既往接受过免疫联合TKI的患者，中位治疗线数为2。研究结果显示，患者客观缓解率约23%，疾病进展比例为34%，这表明部分患者能够从中获益，但另一部分患者则未能改善。值得注意的是，部分患者的缓解持续时间接近两年，且治疗耐受性良好。因此，我认为贝组替凡有望成为既往治疗失败的晚期肾细胞癌患者的单药治疗方案。 然而，关于贝组替凡是否应早期与其他疗法联合应用，仍存在较大争议。来自LITESPARK 003研究的数据显示，贝组替凡与卡博替尼联合使用，未接受任何系统治疗患者的客观缓解率约70%，无进展生存期接近30个月，这提示联合治疗是一种可行的治疗策略。此外，我们还开展了多项研究，探索贝组替凡与免疫疗法及免疫+TKI联合使用的疗效，但目前这些研究的数据尚不成熟。例如，LITESPARK 011研究旨在分析贝组替凡联合仑伐替尼和帕博利珠单抗的效果，我们也在期待这些数据的早日揭晓。 目前，我们已经取得了贝组替凡联合免疫治疗的初步数据，尽管样本量有限，但这些数据表明，贝组替凡联合免疫疗法的无进展生存期可能并不优于其与TKI联合的效果，且协同作用似乎相对较小。未来，我们需要更深入地探究贝组替凡的作用机制，明确其在何种疾病状态下使用最为适宜，以及哪些药物组合能够最大化其疗效。我相信，在接下来的几年里，我们将逐步揭示这些问题的答案，为晚期肾细胞癌的治疗开辟新的篇章。 Yeah, so the approval of Belzutifan in advanced renal cell carcinoma clearly is a great advance for patients with renal cell carcinoma. This study looked at individuals who had received prior therapy, either with an IO agent plus a TKI. They had to have received both, and the median number of treatments that the patients had received was three. What we saw with that study was the objective response rate was around 23%. But the other thing that we did see was that the progressive disease as best response was 34%. So clearly, some people are benefiting, but others not. If patients responded, their responses lasted close to two years, and the treatment is very well tolerated. So I see the future for Belzutifan in advanced renal cell carcinoma as being a monotherapy in individuals who have received prior treatments. But the big question is whether or not Belzutifan should be combined with other therapies in earlier lines of treatment. We have data from LITESPARK-003 that shows that in combination with cabozantinib, there’s an objective response rate of around 70% and a progression-free survival of 30 months in a predominantly favorable-risk population. So maybe combination with cabozantinib is a good idea. We have a number of other studies combining Belzutifan with IO therapies and IO/TKIs, and we don’t have information on those yet. For example, there’s also a study of Belzutifan plus lenvatinib compared to cabozantinib, that’s LITESPARK-011, and we’re waiting for those data. We do have a few data on Belzutifan with IO therapy. There are the KEYMAKER studies that are being run right now. Very small numbers, but they show that Belzutifan together with immune therapy does not seem to have quite the same progression-free survival as Belzutifan with TKI. So maybe there is less synergy or additivity between Belzutifan plus immune therapy compared to TKI. I think we need to keep on working very hard on understanding how to use this drug. It’s clearly helpful, and which combinations are going to be best and in which disease state to use, we will find out in the next few years. 上下滑动查看 往期推荐 1 ASCO GU丨龚侃教授&Eric Jonasch教授共话肾癌相关治疗新策略与展望（上篇） 注：ASCO GU：美国临床肿瘤学会泌尿生殖系统癌症研讨会ccRCC：透明细胞肾细胞癌VHL：Von Hippel－Lindau，希佩尔－林道综合征HIF-2α：低氧诱导因子2αFDA：美国食品药品监督管理局Belzutifan：贝组替凡EPO：促红细胞生成素PPGL：嗜铬细胞瘤/副神经节瘤EAU：欧洲泌尿外科协会AUA：美国泌尿外科协会MDT：多学科诊疗团队RCC：肾细胞癌 TKI：酪氨酸激酶抑制剂 龚侃 教授 教授、博导、主任医师 北京大学泌尿外科研究所副所长  北京大学第一医院肿瘤转化中心副主任 北京大学第一医院科研处处长 国家高层次人才特殊支持计划（中组部万人） 科技部“中青年科技创新领军人才” 教育部“新世纪优秀人才 中华医学会泌尿外科分会肿瘤学组委员 中华医学会泌尿外科分会转化学组副组长 中华医学会罕见病分会第一届委员会委员 中国医促会泌尿外科分会副主任委员 中华医学会泌尿外科分会遗传及罕见病协作组组长 中国医师协会泌尿外科肿瘤委员会委员 中国抗癌协会家族遗传性肿瘤专业委员会常务委员 中国研究型医院学会罕见病分会常务理事 北京医学会肿瘤专业委员会常务委员 北京医学会罕见病分会专业委员会常务委员 国际VHL联盟咨询委员 长期致力于泌尿生殖系统肿瘤的罕见疑难病的诊、防、治攻关研究，主持科技部重大项目课题、国自然重点专项和面上基金、北京市自然科学基金等20余项。在Cancer Discovery、PNAS、Cancer Research等权威杂志发表SCI论文100余篇，授权发明专利3项，其中1项成功转化成产品上市。 Eric Jonasch 教授 MD安德森癌症中心VHL临床中心主任 Eric Jonasch医学博士是德克萨斯大学MD安德森癌症中心癌症医学部泌尿生殖医学肿瘤学系教授。Jonasch博士还担任MD安德森癌症中心的Von Hippel–Lindau(VHL)临床中心主任和MD安德森癌症中心肾癌研究项目联合主任。 Jonasch博士的临床兴趣集中在肾细胞癌和VHL疾病的组织转化研究。他领导了这些疾病的多项研究者发起的临床试验和正在进行的实验室研究工作，以评估对靶向疗法的反应和耐药性的决定因素。Jonasch博士是美国癌症研究协会、美国临床肿瘤学会等成员。 Jonasch 博士目前担任NCCN肾癌小组副主席。 （来源：《肿瘤瞭望-泌尿时讯》编辑部） 声 明 凡署名原创的文章版权属《肿瘤瞭望》所有，欢迎分享、转载。本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。

BridgeBio Pharma has received European approval for a drug that treats cardiomyopathy stemming from a rare metabolic condition, strengthening the biotech’s position to take market share from the blockbuster Pfizer drug that is currently the standard treatment. The European Commission granted marketing authorization to acoramidis, which BridgeBio developed as treatment for transthyretin amyloidosis (ATTR), a disease in which a genetic mutation leads to abnormal versions of the liver protein transthyretin (TTR). The misfolded proteins can cause nerve and heart problems. BridgeBio’s acoramidis, which will be commercialized in Europe as Beyonttra, is a small molecule designed to stabilize TTR to treat the cardiomyopathy caused by the disease. The biotech contends its drug is a better stabilizer than the drugs marketed by Pfizer. For 2024, Pfizer reported $3.3 billion in revenue from its Vyndaqel family of TTR stabilizers, a 36% increase compared to 2023. The FDA approved the BridgeBio TTR drug this past November and it is marketed in the U.S. under the brand name Attruby. In a prescriptions update included in its report of fourth quarter and full year 2024 financial results, BridgeBio said that as of Feb. 17, 1,028 unique patient prescriptions for the drug have been written by 516 unique prescribers since the U.S. approval. That’s an increase from what the company reported last month during the annual J.P. Morgan Healthcare Conference last month, which Leerink Partners said indicates a broadening prescriber base. presented by Health IT Transforming Patient Care: The Role of AI-Powered Assistants The progress in artificial intelligence (AI) is reshaping patient care, across various dimensions, from facilitating faster discharge to curating treatment plans and suggesting lifestyle changes. By IT Medical In Europe, the BridgeBio drug will be commercialized by Bayer per terms of an agreement signed last year. BridgeBio is in line to receive milestone payments and royalties from sales. The first payment is $75 million for the European approval. Here’s a recap of other recent regulatory developments: More Rare Disease Drug Approvals —The FDA approved Mirum Pharmaceuticals drug chenodiol, brand name Ctexli, for treating rare lipid storage disease cerebrotendinous xathomatosis (CTX). This genetic metabolic disorder results in deficient levels of an enzyme important for breaking down fats. Chenodiol is a naturally occurring human bile acid. Under the brand name Chenodal, chenodiol has been marketed for treating gallstones, but it has been used off label as a treatment for CTX. The new FDA approval makes Ctexli the first FDA-approved treatment for CTX. Mirum acquired the drug from Travere Therapeutics in 2023. Sponsored Post Tips for Greater Healthcare Practice Success in 2025 Join us on February 26 at 3 pm ET, and we’ll dive into the key areas where practices are losing time and money and provide solutions to overcome them. By Elation Health and MedCity News —The European Commission approved Livdelzi, a Gilead Sciences drug developed for the rare liver disease primary biliary cholangitis (PBC). The conditional marketing authorization covers use of the daily pill in combination with ursodeoxycholic acid, an older drug that is the standard PBC treatment. The European decision for Livdelzi follows FDA approval of the drug last August. Livdelzi comes from Gilead’s $4.3 billion acquisition of Cymabay Therapeutics last year. —The FDA approved SpringWorks Therapeutics drug Gomekli as a treatment for tumors caused by the rare genetic disorder neurofibromatosis type 1 (NF1). The approval covers treatment of these tumors in both adults and children. That’s an advantage over AstraZeneca’s Koselugo, which is only approved for treating pediatric NF1 patients. —CSL’s garadacimab received approvals in Europe and Japan for treating adults and adolescents age 12 and older who have hereditary angioedema (HAE). The rare disease leads to swelling attacks in tissue beneath the skin. This swelling can close off the airway, putting a patient at risk of death. CSL’s drug, brand name Andembry, is an antibody engineered to inhibit activated Factor XII, a protein that starts the cascade of events leading to unpredictable HAE swelling attacks. Andembry is still under regulatory review in the U.S., Canada, and Switzerland. —Evrysdi, a drug marketed by Roche for the rare disease spinal muscular atrophy, is now approved in a tablet formulation. The product, which was initially developed by PTC Therapeutics and later partnered with Roche, was first approved in 2020 as a liquid administered via an oral syringe or through a feeding tube. The liquid formulation must be refrigerated and kept away from light. The new Evrysdi tablet offers patients a simpler dosing option that can be stored at room temperature. Cancer Drug Approvals —Merck’s Welireg is now approved in Europe as a treatment for adults with von Hillel-Lindau (VHL) disease, a rare genetic disorder that causes benign tumors in the body that can become cancerous. The European Commission’s conditional approval covers patients whose VHL is unsuitable for surgery and requires therapy for renal cell carcinoma, central nervous system hemangioblastomas, or pancreatic neuroendocrine tumors. The commission’s decision also covers the treatment of adults with advanced clear cell renal cell carcinoma that has progressed after two or more lines of therapy. Welireg is a once-daily pill designed to block HIF-2 alpha, inhibiting this protein’s ability to contribute to cancer progression. The FDA approved Welireg in 2021. —The FDA approved Romvimza, an Ono Pharmaceutical drug for tenosynovial giant cell tumor (TGCT). The drug, which came to Ono via the 2024 acquisition of its developer, Deciphera Pharmaceuticals, offers more convenient dosing and a lower risk of liver toxicity compared to Turalio, a Daiichi Sankyo drug that was the first approved systemic therapy for TGCT. —Datroway, a TROP-2-targeting antibody drug conjugate (ADC) from partners AstraZeneca and Daiichi Sankyo, landed FDA approval for treating advanced and unresectable breast cancer that’s classified as HR positive and HER2 negative. It will compete with Trodelvy, Gilead Sciences’ TROP-2-targeting ADC is already approved in the same indication. —Axsome Therapeutics’ Symbravo won FDA approval for acute treatment of migraine with or without aura in adults. The tablet pairs two compounds that target multiple pathways behind a migraine attack. Symbravo is made with proprietary Axsome technology that enables the drug to more quickly achieve maximum concentration in the blood and to maintain a long half-life. Symbravo’s label carries a black box warning for cardiovascular and gastrointestinal risks. The approval marks a comeback for the drug, which received an FDA complete response letter in 2022 due to manufacturing issues. —Foundation Medicine received FDA approval for FoundationOne CDx as a companion diagnostic for the brain cancer drug Ojemda. The test detects the BRAF V600 mutation addressed by the drug, developed by Day One Biotherapeutics. The FDA approved Ojemda last April as a treatment for advanced cases of pediatric low-grade glioma. —Adcetris, an antibody drug conjugate (ADC) developed by Pfizer subsidiary Seagen, added to its label the treatment of advanced cases of diffuse large B-cell lymphoma (DLBCL). The new approval covers use of the drug in combination with the cancer drugs Revlimid and Rituxan. The new FDA approval is based on Phase 3 results showing the Adcetris regimen led to a 37% reduction in risk of death compared to Revlimid, Rituxan, and a placebo. Adcetris was first approved in 2011 for Hodgkin lymphoma and systemic anaplastic large cell lymphoma. The drug now has eight FDA approvals in cancer. Pfizer has rights to the drug in the U.S. and Canada; Takeda Pharmaceutical has rights to the product in the rest of the world. —Blockbuster AstraZeneca cancer drug Calquence, first approved in 2017 for treating advanced mantle cell lymphoma after at least one prior line of therapy, is now approved as a first-line treatment for this rare and aggressive blood cancer. The drug, a BTK inhibitor, is the first in its class approved as a first-line MCL treatment. —Amgen cancer drug Lumakras expanded its FDA approval to metastatic colorectal cancer that is positive for the KRAS G12c mutation and is also unresponsive or resistant to chemotherapy. The regulatory nod in this indication covers use of the daily pill in combination with Vectibix, an Amgen antibody drug approved for colorectal cancer. Lumakras was initially approved in 2022 as a treatment for non-small cell lung cancer driven by the KRAS G12C mutation. Approvals in Immunology —Galderma drug Nemluvio received European Commission approval as a treatment for the inflammatory skin disorders atopic dermatitis and prurigo nodularis. The once-monthly injection is an antibody designed to block IL-31 signaling. The FDA approved Nemluvio for prurigo nodularis and atopic dermatitis last year. —Eli Lilly’s Omvoh, a biologic drug first approved in 2023 as a treatment for ulcerative colitis, added moderately to severely active Crohn’s disease to its label. The drug is an antibody that targets IL-23p19, a protein that contributes to gastrointestinal inflammation. Regulatory submissions in Crohn’s are currently under review in Europe and Japan. In ulcerative colitis, the drug is approved in 44 countries. —Palforzia, a peanut allergy immunotherapy marketed by Stallergenes Greer, expanded the product’s approved uses in Europe to include the treatment of children ages 1 through 3. The initial approval for Palforzia covered children age 4 through 17. The new approval in Europe comes about six months after the therapy secured a similar regulatory decision from the FDA. Privately held Stallergenes Greer added Palforzia to its allergy products portfolio via a 2023 deal with Nestlé. Approvals for Neuro, Pain Meds —Supernus Pharmaceuticals received FDA approval for Onapgo, a drug/device combination product that continuously infuses the drug apomorphine to treat the “off” episodes experienced by Parkinson’s disease patients. Onapgo joins a Supernus Parkinson’s drug lineup that includes Apokyn, an injection pen product that administers apomorphine, and Gocovri, a capsule approved to treat dyskinesia and off time in Parkinson’s patients. —Vertex Pharmaceuticals’ non-opioid drug Journavx won FDA approval as a first-in-class treatment for moderate-to-severe acute pain in adults. The twice-daily pill targets NaV1.8, a pathway in the peripheral nervous system. By stopping pain signals in the periphery before they reach the brain, drugs in this class are intended to avoid the addiction risks poised by opioids, which hit targets in the brain. —The FDA approved Johnson & Johnson’s Spravato as a monotherapy for adults with treatment-resistant depression. The nasal spray drug’s initial approval in 2019 covered its use in combination with an oral antidepressant for treatment-resistant depression in adults. Vaccine Approvals —Bavarian Nordic received FDA approval for its virus-like particle chikungunya vaccine, which will be marketed under the brand name Vimkunya. The FDA nod covers use of the vaccine in those age 12 and older. That’s a broader range than Valneva’s Ixchiq, which became the first FDA-approved chikungunya vaccine in 2023. Ixchiq is indicated for use in those age 18 and older. Bavarian Nordic’s new approval was accompanied by a tropical disease priority review voucher, which the company said it plans to sell. —A GSK vaccine covering five groups of bacteria that cause meningococcal disease is now FDA approved for use in those ages 10 through 25. The vaccine, brand name Penmenvy, combines components of two already available GSK meningococcal vaccines, Bexsero and Menveo. Penmenvy will now compete with Pfizer’s Penbraya, which also covers five bacterial groups. Both vaccines are administered as two intramuscular injections given six months apart. —A Covid-19 vaccine developed by partners Arcturus Therapeutics and CSL is now approved in Europe. The vaccine, brand name Kostaive, employs self-amplifying RNA. Unlike traditional mRNA vaccines, self-amplifying RNA vaccines instruct the body to make more mRNA and protein to boost the immune response. Kostaive was originally developed by Arcturus. In 2022, CSL paid $200 million up front to collaborate on the vaccine. Per deal terms, Arcturus is responsible for regulatory filings in the U.S. and Europe as well as R&D of next-generation vaccine candidates. CSL subsidiary Seqirus takes the lead on all other R&D in Covid-19, influenza, and other fields. More Regulatory Approvals —Izervay, a geographic atrophy drug marketed by Astellas Pharma, is now approved for longer dosing. The product’s initial 2023 approval permitted the once-monthly eye injection to be administered for up to 12 months. The new approval removes the 12 month restriction. However, the Astellas product did not receive the FDA O.K. for every-other-month administration. That additional flexibility would have put it on par with Apellis Pharmaceuticals’ geographic atrophy drug Syfovre, which is approved for monthly and every-other-month dosing. —Novo Nordisk drug Ozempic is now approved for treating chronic kidney disease in patients with type 2 diabetes. The blockbuster drug was initially approved for type 2 diabetes, which is a risk factor for chronic kidney disease. In the pivotal study supporting the latest regulatory nod, Ozempic led to a 24% reduction in kidney disease complications compared to a placebo. —AbbVie’s pairing of the antibiotics aztreonam and avibactam received FDA approval for the treatment of complicated intra-abdominal infections, giving clinicians another tool to address antimicrobial resistance. The therapy, which will be marketed under the brand name Emblaveo, is indicated for use in combination with Flagyl, a Pfizer antibiotic. Emblaveo was developed in partnership with Pfizer. AbbVie has commercialization rights to the drug in the U.S and Canada; Pfizer is responsible for the antibiotic’s commercialization in the rest of the world. Clinical Holds and Regulatory Setbacks —The FDA sent Harmony Biosciences a refuse to file letter for pitolistant, a drug the biotech is seeking to commercialize as a treatment for excessive daytime sleepiness in adults who have idiopathic hypersomnia. In a Phase 3 withdrawal study, the once-daily tablet did not achieve statistical significance compared to placebo. The biotech said a Phase 3 registrational study in idiopathic hypersomnia is on track to begin in the fourth quarter of this year. Pitolistant is already available as a treatment for excessive daytime sleepiness or cataplexy in adults with narcolepsy, marketed as Wakix in this indication. —Moderna’s Phase 3 test of its two-season norovirus vaccine candidate, mRNA-1403, is under an FDA clinical hold. The company said the clinical trial halt is due to a single report of Guillain- Barré syndrome, nerve damage that can be a complication of vaccines. The adverse event is under investigation. The company does not expect the clinical hold will affect the trial readout timeline in the northern hemisphere, where the study is already fully enrolled. The timing of a data readout will depend on case accruals. Second season enrollment is being prepared in the southern hemisphere. —The FDA placed a clinical hold on Ebvallo, a treatment for advanced cases of Epstein-Barr virus positive post-transplant lymphoproliferative disease. The hold came days after the FDA rejected the immunotherapy due to findings from an inspection of a third-party manufacturing facility. The company said the Ebvallo clinical hold relates to the issues flagged in the complete response letter. Ebvallo, which is made by engineering T cells from healthy donors, was approved in Europe in 2022.