Altimmune 肝病药 pemvidutide 二期48周结果登《柳叶刀》子刊：肝脂肪、炎症与纤维化指标显著下降
美国新泽西州 Morristown 的生物制药公司 Altimmune（Nasdaq: ALT）11月12日宣布，其在研药物 pemvidutide 治疗代谢功能障碍相关脂肪性肝炎（MASH）的 IMPACT 2b 期试验 48 周结果，已正式发表于《柳叶刀·胃肠病学与肝病学》。48 周时，pemvidutide 在肝脂肪、肝脏炎症与纤维化多项无创指标上较安慰剂显著下降，并伴有显著减重。
IMPACT 是一项随机、双盲、安慰剂对照试验，共纳入 212 名经活检确诊、纤维化分期 F2 或 F3 的 MASH 患者，伴或不伴糖尿病，按 1:2:2 分配至每周皮下注射 pemvidutide 1.2 毫克、1.8 毫克或安慰剂，疗程 48 周。此前公布的 24 周结果已达到主要终点，即 MASH 消退且纤维化不恶化；本次发表的是 48 周的次要终点数据，包括 MASH 消退与纤维化改善。
试验主要研究者、休斯敦 Methodist 医院医学教授 Mazen Noureddin 表示，发表的结果显示，治疗早期出现的改善在多项肝脏健康指标上继续扩大，包括炎症，尤其是纤维化，而纤维化对 MASH 的长期结局起关键作用；肝脏获益同时伴有减重与血糖控制维持，胃肠道耐受性总体良好，心率无显著变化，这些结果为正在进行的 PERFORMA 3 期试验打下基础。
安全性方面，pemvidutide 在不做剂量递增的情况下给药 48 周，耐受性总体良好，接受治疗的患者中约 1% 因不良事件停药；不良事件多为轻至中度，胃肠道事件多为轻至中度、主要出现在最初 8 周，心脏不良事件与安慰剂组相比未见失衡。1.8 毫克组的减重在 48 周疗程结束时仍在继续。
Pemvidutide 是一种胰高血糖素与 GLP-1 受体 1:1 平衡双激动剂在研肽类药物，已获 FDA 授予 MASH 与酒精使用障碍的快速通道认定，以及 MASH 的突破性疗法认定。公司 2025 年 12 月曾公布 IMPACT 48 周顶线数据，针对 MASH 的全球 3 期试验 PERFORMA 已于 2026 年 7 月启动。（来源：Altimmune）
Altimmune Publishes IMPACT Phase 2b 48-Week MASH Data in The Lancet Gastroenterology & Hepatology: Significant Reductions in Liver Fat, Inflammation and Fibrosis
Altimmune, Inc. (Nasdaq: ALT), a biopharmaceutical company based in Morristown, New Jersey, on November 12 announced the publication of 48-week results from the IMPACT Phase 2b trial of pemvidutide in metabolic dysfunction-associated steatohepatitis (MASH) in The Lancet Gastroenterology & Hepatology. At Week 48, pemvidutide produced significant reductions versus placebo across multiple non-invasive measures of liver fat, hepatic inflammation and fibrosis, together with significant weight loss.
IMPACT was a randomized, double-blind, placebo-controlled trial that enrolled 212 participants with biopsy-confirmed MASH and fibrosis stages F2 or F3, with and without diabetes. Participants were randomized 1:2:2 to weekly subcutaneous pemvidutide at 1.2 mg or 1.8 mg, or placebo, for 48 weeks. The previously reported 24-week results met the primary endpoint of MASH resolution without worsening of fibrosis; the newly published paper reports 48-week secondary endpoints, including MASH resolution and fibrosis improvement.
Mazen Noureddin, M.D., the IMPACT trial's principal investigator and a professor of medicine at Houston Methodist Hospital, said the published results show that improvements seen earlier in treatment increased across multiple measures of liver health, including inflammation and, importantly, fibrosis, which plays a key role in long-term outcomes in MASH. Liver benefits were accompanied by weight loss and maintenance of glycemic control, with generally favorable gastrointestinal tolerability and no significant change in heart rate, providing a strong foundation for the ongoing PERFORMA Phase 3 trial, he said.
On safety, pemvidutide showed a generally favorable tolerability profile over 48 weeks despite being administered without dose titration. Approximately 1% of patients receiving pemvidutide discontinued treatment due to adverse events. Most adverse events were mild to moderate; gastrointestinal events were mostly mild to moderate and occurred predominantly within the first 8 weeks, and no imbalances in cardiac adverse events were observed versus placebo. Weight loss with the 1.8 mg dose appeared to continue through the end of the 48-week treatment period.
Pemvidutide is an investigational peptide with balanced 1:1 glucagon and GLP-1 dual receptor agonist activity. The FDA has granted it Fast Track designations for MASH and alcohol use disorder, as well as Breakthrough Therapy Designation for MASH. The company announced topline 48-week IMPACT data in December 2025, and the global PERFORMA Phase 3 trial in MASH was initiated in July 2026. (Source: Altimmune)
来源：Altimmune
发布：GSM·美国（发布链接）
图片来源：图：人体肝脏示意图。NIH BioArt（NIAID 供图），Wikimedia Commons，公共领域。 / Image: Illustration of the human liver. NIH BioArt, courtesy of NIAID, via Wikimedia Commons, public domain.
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