Glepaglutide

12月20日 产品：礼来的Zepbound（Tirzepatide） 适应症：成人肥胖症的中度至重度阻塞性睡眠呼吸暂停 礼来的Zepbound已经是减肥领域的一枚重磅炸弹，现在还可用于治疗肥胖成人的中度至重度阻塞性睡眠呼吸暂停，并指出该药物将与饮食和运动相结合。根据该机构的新闻稿，该批准标志着某些患有这种疾病的患者的第一治疗选择。 批准基于两项随机、双盲、安慰剂对照研究——一项使用气道正压通气（PAP）的成人，另一项未进行PAP治疗。469名参与者中无人患有2型糖尿病。 在每周一次Zepbound（10或15mg）或安慰剂52周后，服用Zepbound的参与者的呼吸暂停或低通气事件减少了，具有统计学意义和临床意义。这些好处伴随着体重减轻，FDA表示这可能有助于改善呼吸暂停症状。 12月20日 产品：Vertex Pharmaceuticals（福泰制药）的Alyftrek 适应症： 患有囊性纤维化且至少有一个F508del突变或对治疗有反应的 CFTR 基因中的另一个突变的成人和6岁及以上儿童 与Trikafta一样，新批准的产品Alyftrek也是一种三联疗法，不过，这些产品只共享一种活性成分，Vertex表示，Alyftrek中使用的药物组合比Trikafta有优势，后者在2023年的销售额为89亿美元。 12月20日 产品：诺和诺德的Alhemo 适应症： 患有血友病A或B的成人和12岁及以上儿童 在去年被FDA拒绝后，诺和诺德的Alhemo已获得监管机构的批准，用于预防成人和12岁及以上血友病A或B儿童的出血发作或降低出血频率，这些血友病A或B已经产生抑制剂，这些抑制剂是中和凝血因子的抗体，如因子VIII或因子IX。据Novo称，大约30%的严重血友病A患者和5-10%的严重血友病B患者会出现抑制物。 Alhemo是一种抗组织因子通路抑制剂，每天一次皮下注射，可提高凝血蛋白凝血酶的水平。该批准得到了一项关键试验的支持，在该试验中，与对照组相比，Alhemo将治疗的自发性和创伤性出血的频率降低了86%。 Alhemo将与辉瑞每周一次的皮下血友病治疗药物Hympavzi竞争，后者于10月获得FDA批准。据 EndpointsNews报道，Hympavzi仅被批准用于没有抑制剂的血友病A和B患者，但辉瑞预计明年将获得Hympavzi在有抑制剂患者中的数据，这可能支持标签扩展。 12月20日（拒绝） 产品：Zealand Pharma的格列帕鲁肽glepaglutide 适应症：短肠综合征 根据FDA的完整回复函，要求提供更多证据以确认glepaglutide在其拟议剂量下的疗效和安全性，并建议Zealand进行另一项临床试验来生成这些数据。 Zealand首席营销官David Kendali在一份声明中表示，该公司对拒绝感到失望，但对glepaglutide和支持其用于治疗短肠综合征的证据仍有信心。他说，Zealand将继续与FDA合作，“在获得监管批准的道路上保持一致”。这家生物技术公司还着眼于明年向欧洲药品管理局提交监管申请。 短肠综合征的特征是小肠被截断或受损，使患者无法从食物中充分吸收营养，通常依赖肠外支持。Zealand提议使用glepaglutide治疗这些患者，并以一项随机、安慰剂对照的后期试验的数据支持其监管投标。每周两次格列帕鲁肽在减少患者肠外支持需求方面显著优于安慰剂，尽管每周一次的给药方案未能达到统计学意义。 12月19日 产品：Ionis的Tryngolza 适应症：家族性乳糜微粒血症综合征(FCS)成人患者的甘油三酯(TG)。 Ionis制药公司于2024年12月19日宣布，美国食品药品监督管理局(FDA)已批准其反义寡核苷酸(ASO)疗法Tryngolza(olezarsen)，用于作为饮食控制的辅助治疗，以降低家族性乳糜微粒血症综合征(FCS)成人患者的甘油三酯(TG)。 Olezarsen是一种反义寡核苷酸疗法，旨在抑制机体产生载脂蛋白C-III(apoC-III)——这是一种在肝脏中产生的、可调节血液中甘油三酯(TG)代谢的蛋白。这是FDA批准的首个治疗药物，可显著降低患有家族性乳糜微粒血症综合征(FCS)的成人的甘油三酯水平，并在与适当的饮食(每天≤20克脂肪)一起使用时，提供具有临床意义的急性胰腺炎(AP)事件减少。 12月18日 产品：Xcovery的Ensacove 适应症：ALK阳性局部晚期或转移性非小细胞肺癌 Xcovery Holdings获得了 FDA的批准，Ensacove（Ensartinib）用于治疗局部晚期或转移性非小细胞肺癌（NSCLC）患者，这些患者对间变性淋巴瘤激酶（ALK）融合基因也呈阳性。Ensacove已获准用于一线治疗。 ALK是一个主要参与发育的基因，在健康的情况下，它在出生前就被关闭了。然而，在某些情况下，该基因被重新激活并与邻近基因融合——这种突变可导致不同类型的癌症，例如淋巴瘤和NSCLC。 Ensacove 是一种口服酪氨酸激酶抑制剂，通过破坏ALK介导的信号传导来解决ALK阳性NSCLC，进而阻断癌细胞典型的过度活跃的生长和增殖。 Xcovery在III期eXalt3研究中研究了Ensacove，其数据于2021年9月发表在《美国医学会杂志·肿瘤学》（JAMA Oncology）上。在该试验中，Ensacove显著改善了辉瑞的Xalkori（克唑替尼）的无进展生存期。 12月18日 产品：Celltrion的Steqeyma 适应症：成人和儿童斑块状银屑病和银屑病关节炎、成人克罗恩病和溃疡性结肠炎 在FDA批准了Celltrion的生物仿制药Steqeyma之后，强生公司将面临对其重磅免疫疗法Stelara（优特克单抗）的更激烈竞争。 与其品牌参考产品一样，Steqeyma可用于治疗斑块状银屑病和银屑病关节炎的成人和儿童患者，以及患有克罗恩病和溃疡性结肠炎的成人患者。Steqeyma于2025年2月在美国上架，将以皮下注射和静脉输注的形式提供。 根据Celltrion的说法，Steqeyma的批准部分基于斑块状银屑病的III期研究结果，该研究表明，该生物仿制药在疗效或安全性方面与Stelara没有临床意义的差异。 Steqeyma是不断增长的Stelara生物仿制药列表中的最新成员。4月，FDA还批准了Teva和Alvotech的Selarsdi，该药可用于斑块状银屑病和银屑病关节炎，但不能用于克罗恩病和溃疡性结肠炎。Selarsdi将于2025年初推出。 12月18日（拒绝） 产品：阿斯利康的Andexxa 适应症：抗凝治疗的逆转 根据 PinkSheet 上周的报道，FDA拒绝对阿斯利康的重组因子Xa疗法Andexxa给予批准。该制药公司已向各种媒体证实了拒绝反应，同时指出该药物仍将提供给患者。 Andexxa于2018年获得FDA的加速批准，用于阻止接受利伐沙班或阿哌沙班抗凝治疗的患者的出血。为了证实Andexxa的临床益处，阿斯利康使用了 IV期ANNEXA-I研究的数据，该研究发现，与常规护理相比，该药物可以显着改善急性颅内出血患者的止血效果。 然而，在上个月的FDA细胞、组织和基因疗法咨询委员会会议上，外部专家发现ANNEXA-I的数据是需要的，特别是它对需要凝血支持的特定患者群体的关注。小组成员发现，很难利用ANNEXA-I的发现来提出监管建议，这些建议会影响更广泛的可以使用Andexxa的患者。 在委员会会议前的一份简报文件中，FDA的内部审查员指出，与标准护理相比，接受Andexxa治疗的患者发生血栓形成和相关死亡的风险会更高。 12月17日 产品：Galderma的Nemluvio 适应症：中度至重度特应性皮炎 FDA颁发了一对特应性皮炎点头，其中一份给了Galderma及其皮下注射剂Nemluvio（nemolizumab-ilto），该注射剂适用于 12岁及以上患有中度至重度特应性皮炎的患者。 根据其标签，建议将Nemluvio与局部皮质类固醇和/或钙调磷酸酶抑制剂一起给药。 Nemluvio是一种人源化IgG2单克隆抗体，靶向IL-31受体并破坏其下游信号传导，进而抑制炎症、纤维化和表皮失调。它的批准得到了III期ARCADIA临床试验计划的支持，该计划包括1700多名患者，发现与安慰剂相比，每4周给药一次的Nemluvio可显着改善皮肤清除率。与安慰剂相比，Nemluvio还显著缓解了瘙痒和减少了睡眠障碍。 Galderma的目标是Nemluvio的峰值销售额超过20亿美元，这家生物技术公司预计到2027年底将达到重磅炸弹的地位。 12月17日 产品：Organon的Vtama 适应症：特应性皮炎 Organon报告说，FDA已批准其外用乳膏Vtama（taparinof）用于治疗特应性皮炎。Vtama可用于成人患者和年仅2岁的儿童。 Vtama是一种芳烃受体激动剂，根据该药物的标签，其确切的作用机制尚未完全阐明。Vtama 于2022年5月首次被批准用于治疗斑块状银屑病。 Organon用ADORING关键试验的结果支持Vtama的应用，该试验确定了该面霜在帮助患者获得清晰或几乎清晰的皮肤方面优于载体。此外，一项长期扩展研究确定Vtama的效果是持久的，并且在48周的随访中其耐受性仍然良好。 对于Vtama的批准，Organon首席执行官凯文·阿里（KevinAli）在一份声明中表示，“现在有一种疗法具有强大的皮肤清除潜力，没有标签警告或预防措施、禁忌症，也没有对使用持续时间或受影响体表面积百分比的限制。 12月16日 产品：Neurocrine的Crenessity 适应症：先天性肾上腺皮质增生症 Neurocrine的Crenessity（crinecerfont）在提前获得批准，成为该行业70年来第一种新型先天性肾上腺皮质增生症（CAH）的治疗药物。 CAH是一种罕见的遗传病，其特征是缺乏重要的肾上腺类固醇激素，包括皮质醇、醛固酮和肾上腺雄激素。CAH患者会出现脱水和呕吐，严重时会导致盐分浪费甚至死亡。在Crenessity获得批准之前，患者及其提供者使用糖皮质激素控制症状，糖皮质激素可以帮助纠正酶失衡，但可能会带来骨质疏松症和糖尿病等副作用。 Crenessity通过选择性阻断CRF1受体来帮助调节过量的ACTH和其他肾上腺雄激素。其批准得到了III期CAHtalyst研究数据的支持，该研究表明Crenessity显着降低了成人和儿童患者的雄烯二酮浓度，使他们能够在不影响治疗效果的情况下逐渐减少糖皮质激素剂量。 然而，BMO Capital Markets分析师预计启动速度会很慢，他们在给投资者的一份报告中写道，挑战包括“急性肾上腺皮质功能不全或肾上腺危象伴伴糖皮质激素治疗不足的风险”的黑框警告。该公司表示，预计要到2025年下半年才能实现广泛的商业准入。 12月16日 产品：Checkpoint Therapeutics的Unloxcyt 适应症：转移性或局部晚期皮肤鳞状细胞癌 FDA批准使用CheckpointTherapeutics的PD-L1抑制剂Unloxcyt治疗转移性或局部晚期皮肤鳞状细胞癌患者。 据Checkpoint称，Unloxcyt是“第一个也是唯一一个”适用于该适应症的PD-L1阻断剂，首席执行官James Oliviero在一份声明中表示，这家生物技术公司预计将“在估计每年超过10亿美元的美国市场竞争”。Oliviero补充说，与市场上其他已批准的药物相比，Unloxcyt可能是一种差异化的选择，因为它靶向PD-L1而不是PD-1，因为它可以诱导抗体依赖性细胞介导的细胞毒性。 Unloxcyt的批准得到了关键数据的支持，该数据显示，转移性和局部晚期疾病患者的确认客观缓解率分别为 47.4%和54.8%。 该批准也是在2023年12月因与第三方合同制造商的问题有关而被拒绝之后获得的。 12月5日 产品：阿斯利康的Imfinzi 适应症： 局限期小细胞肺癌 阿斯利康成功扩大了其PD-L1阻滞剂Imfinzi（durvalumab）的标签，获得了FDA的批准，用于同时接受铂类化疗和放疗后未进展的局限期小细胞肺癌患者。 该批准得到了III期ADRIATIC研究数据的支持，根据 2024年4月的数据，该研究达到了总生存期和无进展生存期（PFS）的主要疗效终点。虽然阿斯利康当时没有披露具体数据，但FDA在周三的新闻稿中表示，与安慰剂相比，Imfinzi治疗可将死亡风险降低27%，同时将PFS降低24%。两种效应均具有统计学意义。 8月，FDA还批准 Imfinzi用于非小细胞肺癌患者的围手术期治疗——尽管人们对手术前后是否需要暴露PD-L1持怀疑态度。 12月5日 产品：Merus的Bizengri 适应症： 具有 NGR1 突变的胰腺癌和非小细胞肺癌 Merus的双特异性抗体zenocutuzumab成为晚期不可切除或转移性胰腺癌和具有 NRG1 基因融合的NSCLC的“第一个也是唯一一个”疗法。FDA在其加速途径下批准了zenocutuzumab（现在将作为Bizengri销售）。Merus需要在验证性试验中验证Bizengri的临床益处，以使其继续投放市场。 Bizengri通过与HER2和HER3的胞外结构域结合起作用，这两种结构域通常都在肿瘤细胞上表达。这种作用机制阻止了这两种蛋白质的二聚化并阻断了NRG1与HER3的结合，进而减少了细胞增殖并促进了免疫系统的癌症杀伤活性。 FDA的加速批准得到了eNRGy研究的支持，该研究称胰腺癌和NSCLC患者的总体缓解率分别为40%和33%。前者患者组的反应持续时间长达16.6个月，而后一组的中位持续时间为7.4个月。 12月3日 产品：BioconBiologics的Yesintek 适应症： 克罗恩病、溃疡性结肠炎、斑块状银屑病和银屑病关节炎 FDA批准了BioconBiologics的Yesintek（ustekinumab-kfce），这是一种与强生公司的重磅抗体Stelara类似的生物仿制药。 与其参考产品一样，Yesintek适用于斑块状银屑病和银屑病关节炎，以及炎症性肠病克罗恩病和溃疡性结肠炎。根据 2024年2月与J&J（强生）的和解协议，Biocon将能够在2025年2月22日之前在美国推出Yesintek。 随着FDA的批准，Yesintek加入了越来越多的Stelara模仿者行列，准备在明年挑战这种重磅药物。其中包括Teva和Alvotech的Selarsdi（于2024年4月获得批准），以及三星Bioepics的Pyzchiva（将由Sandoz商业化）。2024年9月，Cigna的EvernorthHealthServices 宣布将以0美元的价格提供可互换的Stelara生物仿制药替代品，这将给强生带来了更大的压力。 Ref：https://www.biospace.com/biospace-fda-decision-tracker 药事纵横征稿启事

For many people, the end of the year is a mad rush to wrap things up before the holidays, and so it was for the FDA. Notable regulatory decisions include the first drug approval for a prevalent chronic condition and a novel regenerative medicine approach to help trauma patients. In one case, a new drug approval comes as its developer takes on a new identity in the new year. Here’s a look back at some highlights from a busy regulatory month: 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 Notable Firsts —The prevalent sleeping disorder obstructive sleep apnea has historically been managed with a medical device that helps breathing. Eli Lilly’s Zepbound is now the first FDA-approved drug treatment for the chronic condition. Obesity is a risk factor for sleep apnea and clinical trial results showed that weight reductions from treatment with Zepbound were accompanied by breathing improvement. Approval in obstructive sleep apnea adds another potential blockbuster indication for a metabolic medication that has fast become one of Lilly’s top-selling products. —Patients who have the rare inherited metabolic disorder familial chylomicronemia syndrome lack the ability to break down triglycerides, a type of fat from food. The only way to avoid potentially fatal complications to the pancreas is by maintaining an extremely restrictive diet. Approval of Ionis Pharmaceuticals’ olezarsen gives patients a therapeutic option. The once-monthly injected genetic medicine, which is designed to block the body’s production of a liver protein that regulates triglyceride metabolism, will be marketed under the brand name Tryngolza. Ionis previously brought drugs through late-stage development and commercialization under partnerships with larger companies. Tryngolza will be the first product Ionis commercializes on its own. —When trauma to an arm or leg requires replacement of a blood vessel, the standard treatment is grafting a vein from the patient or implanting a synthetic vein. Now there’s a new regenerative medicine option. Humacyte won FDA approval for Symvess, a bioengineered blood vessel for restoring blood flow to avoid the loss of a limb when grafting a vein from the patient is not feasible. Here’s more about the biotech’s regenerative technology. Sponsored Post The Funding Model for Cancer Innovation is Broken — We Can Fix It Closing cancer health equity gaps require medical breakthroughs made possible by new funding approaches. By Eve McDavid - CEO of Mission-Driven Tech —Mesoblast’s regulatory approval was a long time coming. In 2020 and 2023, the FDA turned down the Australian company’s application for remestemcel, an allogeneic cell therapy for graft versus host disease, an immune response that develops when donor T cells attack the recipient’s cells following a transplant procedure. Remestemcel, brand name Ryoncil, is a made from mesenchymal stromal cells sourced from the bone marrow of healthy donors. The product’s approval covers acute graft versus host disease that is refractory to treatment with steroids in patients age 2 months and older. It’s the first affirmative regulatory decision for a cell therapy made from mesenchymal stromal cells. Approvals in Immunology —Vtama, an Organon drug acquired from Roivant Sciences earlier this year, received FDA approval as a treatment for atopic dermatitis in adults and children age 2 and older. The drug is topical cream that was initially approved in 2022 as a treatment for plaque psoriasis. Approval in atopic dermatitis brings the product to a much larger dermatologic indication, albeit one served my many branded and generic medications. —In other atopic dermatitis news, Galderma landed FDA approval for nemolizumab, brand name Nemluvio. The drug is an antibody designed to block IL-31, a signaling protein associated with the itch and inflammation of the chronic skin disorder. FDA approval of Nemluvio covers use of the drug in patients age 12 and older who have moderate-to-severe atopic dermatitis. It’s the second approval in the past year for Nemluvio, which was first approved over the summer as a treatment for prurigo nodularis. Rare Disease Regulatory Decisions —Neurocrine Biosciences received approval for Crenessity, a treatment for the rare inherited hormone disorder congenital adrenal hyperplasia. The small molecule helps bring the hormone imbalance back to more normal levels. The FDA approved a pill formulation for adults and an oral solution for pediatric patients. Analysts project Crenessity could achieve blockbuster sales, pending regulatory approvals in other countries. —Novo Nordisk is best known for metabolic medicines, but its rare disease portfolio is getting a boost with FDA approval of Alhemo, a drug that reduces bleeding episodes in patients with either hemophilia A or B. Alhemo, known in development as concizumab, is an antibody designed to bind to TFPI, preventing that protein from blocking factor Xa, a different protein that plays a role in blood clotting. That’s the same mechanism of action as Pfizer’s Hympavzi, which won its FDA approval in October. Both drugs are subcutaneous injections that provide alternatives to intravenously infused hemophilia therapies. But Pfizer’s once-weekly Hmypavzi has a dosing edge over Alhemo, which must be injected once daily. —Vertex Pharmaceuticals is adding a new cystic fibrosis (CF) drug to its portfolio with FDA approval of Alyftrek, which combines three compounds in a single therapy. Like Vertex’s other CF therapies, Alyftrek is a modulator of the CFTR a protein that regulates the movement of chloride ions into and out of cells. Alyftrek’s approval is based on clinical data comparing the once-daily therapy to Trikafta, a Vertex triple combination drug initially approved in 2019 as a twice-daily CF treatment. Results showed Alyftrek was non-inferior to Trikafta on a key measure of lung function and was superior in reducing sweat chloride levels, which is a surrogate indicator of the function of CFTR proteins. Besides the dosing advantage, Alyftrek addresses 31 additional mutations that are not addressable by other CFTR modulators. The Dec. 20 approval of Alyftrek came nearly two weeks ahead of the Jan. 2 target date for a regulatory decision. Developments in Cancer Drugs —The FDA awarded accelerated approval to Merus Therapeutics drug zenacutuzumab as a treatment for advanced cases of two types of cancer: non-small cell lung cancer and pancreatic adenocarcinoma. It’s the first approval for a drug that addresses a genetic signature called an NRG1 gene fusion. Netherlands-based Merus will market the bispecific antibody under the brand name Bizengri. In a deal struck days prior to the approval announcement, Partner Therapeutics licensed U.S. commercialization rights to Bizengri. —The blockbuster AstraZeneca drug Imfinzi expanded its FDA-approved uses to include limited-stage small cell lung cancer that has not progressed following concurrent platinum-based chemotherapy and radiation therapy. The checkpoint inhibitor was first approved in 2017 for bladder cancer and added extensive-stage lung cancer as a new indication in 2020. The drug’s latest approval is based on Phase 3 results showing a 27% reduction in the risk of death compared to a placebo. AstraZeneca said the FDA decision makes Imfinzi the first immunotherapy approved for limited-stage small cell lung cancer. —Xcovery Holdings drug ensartinib, brand name Ensacove, was approved to treat adults with advanced cases of non-small cell lung cancer that is positive for ALK mutations. Patients prescribed the once-daily pill must not have previously received an ALK inhibitor. —Pfizer cancer drug Braftovi landed accelerated approval as a first-line treatment for metastatic colorectal cancer driven by the BRAF V600E mutation. The approval covers use of the drug in combination with Eli Lilly’s Erbitux and the chemotherapy regimen referred to as FOLFOX, both standard colorectal cancer therapies. Braftovi, a small molecule inhibitor of BRAF V600E, was initially approved in 2018 for advanced cases of melanoma. The drug came from Pfizer’s 2019 acquisition of Array Biopharma. —Tevimbra, a cancer immunotherapy developed by BeiGene, received FDA approval as a first-line treatment for gastric and gastroesophageal junction cancers when used in combination with chemotherapy. It’s the second FDA approval for the checkpoint inhibitor, which was approved last March for treating advanced or metastatic esophageal squamous cell carcinoma after prior treatment with chemotherapy. The new year means a new identity for BeiGene. The cancer drug developer is changing its name to BeOne Medicines. Starting Jan. 2, the company’s stock symbol on the Nasdaq will be “ONC.” Rejections, Warnings & More Bad News in Biotech —Astellas Pharma’s bid to bring patients less-frequent eye injections of its drug Izervay was rejected by the FDA. Izervay, approved for treating geographic atrophy in 2023, is administered monthly to slow progression of the vision-loss disorder. Astellas sought approval for every-other-month dosing based on two-year Phase 3 data. According to Astellas, no safety benefit/risk issues were cited but the FDA took issue with a statistical matter related to labelling language proposed by the company. The rejection will limit Izervay’s ability to compete against Apellis Pharmaceuticals’ geographic atrophy drug Syfovre, which is approved for both monthly and every-other-month dosing. —In other Astellas news, the label for menopause drug Veozah now sports a black box warning for the risk of serious liver injury. The warning follows a FDA safety communication issued in September after a postmarketing report of a patient who developed signs and symptoms of liver injury after taking the once-daily pill for about 40 days. Veozah won FDA approval in 2023 as the first in a new class of therapies for menopause. —Applied Therapeutics received a double dose of bad regulatory news. First the FDA rejected the biotech’s application for govorestat, a drug developed as a treatment for the rare metabolic disease galactosemia. According to Applied, the agency cited “deficiencies in the clinical application.” Days after the FDA complete response letter, the FDA sent Applied a warning letter. The trial and the drug are redacted in the public version of the letter, but in a regulatory filing, Applied acknowledged the FDA’s concerns are about the govorestat galactosemia trial. Applied said the warning letter identified issues with electronic data capture and a dosing error in the dose-escalation portion of the study — both of which the company believed it had already addressed with the agency. Applied said it would respond to the FDA warning letter. —Bad news keeps stacking up for Intercept Pharmaceuticals and its drug, Ocaliva, a treatment for the rare liver disease primary biliary cholangitis (PBC). On Dec. 12, the FDA issued a safety alert, warning of the risk of serious liver injury in patients without advanced liver cirrhosis. The alert came one month after the FDA turned down Intercept’s application seeking full approval for Ocaliva, which won its accelerated approval in PBC in 2016. The FDA’s rejection letter for the drug cited safety concerns. When Ocaliva first reached the market, it was the only FDA-approved second-line treatment for PBC. In the past year, drugs from Ipsen and Gilead Sciences have each won accelerated approvals as new second-line therapies for the rare disease. Two weeks after the FDA turned down full approval of Ocaliva, the European Commission revoked the conditional marketing authorization for the drug. Advanz Pharma holds rights to Ocaliva in Europe. The company said the commission decision is subject to an ongoing annulment procedure in the EU’s General Court and a ruling is expected in 2025. —The FDA turned down Zealand Pharma’s glepaglutide as a treatment for short bowel syndrome, a rare disorder that develops when the small intestine is damaged or shortened, making it difficult for the organ to absorb nutrients. The drug is a long-acting GLP-2 analog intended to enhance the intestine’s ability to absorb nutrients, reducing patients’ dependence on intravenous feeding. According to Zealand, the FDA said the application needed more evidence of efficacy and safety. The company said it would discuss the letter with the FDA and proceed with plans to seek European approval in 2025. —Lexicon Pharmaceuticals came up short in its bid to expand approval of its drug, sotagliflozin (brand name Zynquista), to include the treatment of adults with type 1 diabetes and chronic kidney disease. The FDA’s Dec. 20 rejection of the drug followed a negative FDA advisory committee vote in October. The FDA approved sotagliflozin last year as a treatment for heart failure; it’s marketed in this indication under the brand name Inpefa. —Johnson & Johnson received a complete response letter for its injectable version of Rybrevant, a drug that treats cancer driven by EGFR mutations. Intravenously infused Rybrevant was approved in 2021 as a treatment for non-small cell lung cancer. The injectable version is made with technology from Halozyme. J&J said the FDA letter flagged manufacturing issues and did not cite any concerns about the new formulation or its safety and efficacy.