FASN抑制剂ASC40在中国NASH患者队列中显示出阳性的2期临床研究

StephenW

FASN Inhibitor ASC40 Demonstrates Positive Phase 2 Topline Clinical Results from China Cohort of Patients with NASH

News provided by
Ascletis Pharma Inc.

Mar 08, 2021, 19:30 ET
Share this article

    Oral FASN inhibitor ASC40 shown to meaningfully reduce liver fat with a 50% responder rate
    Consistent improvement in biomarkers of liver inflammation as observed in U.S. cohort

SHANGHAI, China and SAN MATEO, California, March 8, 2021 /PRNewswire/ -- Gannex Pharma Co., Ltd., a wholly-owned company of Ascletis Pharma Inc. (HKEX:1672), and Sagimet Biosciences Inc. jointly announced today positive topline results from the China cohort of a Phase 2 randomized, placebo-controlled clinical trial of oral, once-daily fatty acid synthase (FASN) inhibitor ASC40 (known as TVB-2640 outside of China) that is being evaluated as a potential treatment for nonalcoholic steatohepatitis (NASH). The preliminary data showed that ASC40 meaningfully reduced liver fat, the primary efficacy endpoint of this trial, with a 50% responder rate (patients achieving ≥30% reduction). Participants also showed robust improvement in ALT, a liver enzyme associated with inflammation. These data from the China cohort are consistent with those of the U.S. cohort, previously reported at the AASLD Liver Meeting in November 2020.

"I am pleased that the first Phase 2 NASH trial in mainland China has been completed on schedule and resulted in positive data," said Dr. Junping Shi, Deputy Dean of the Affiliated Hospital of Hangzhou Normal University, Deputy Leader of the Fatty Liver and Alcoholic Hepatology Group of the Chinese Medical Association Hepatology Branch, principal investigator of ASC40 (TVB-2640) Phase 2 trial in China. "Based on the positive Phase 2 data, we have selected doses for the Phase 2b/3 NASH trial in China."

The China cohort of this Phase 2 trial evaluated the safety and efficacy of an oral, once-daily dosing of 50 mg of ASC40 or matching placebo for 12 weeks in 30 patients with NASH. Trial participants were required to have at least 8% liver fat at baseline, as measured by magnetic resonance imaging-proton density fat fraction (MRI-PDFF), and evidence of stage F1 to F3 liver fibrosis on liver biopsy or characteristics of metabolic syndrome. The study demonstrated a relative reduction in liver fat of 28.2% in the ASC40 group versus a reduction of 11.1% in the placebo group. ASC40 also showed a statistically significant decrease in ALT by 29.8% (p=0.0499) (mean decrease of 33 U/L at week 12), which indicates reduction of liver inflammation. In 63% of patients on ASC40, ALT decreased by17 U/L or greater, which has been shown to correlate with liver biopsy response in NASH patients.

ASC40 was well tolerated with no serious adverse events. All treatment emergent adverse events were grade 1 or 2 and there were no statistically significant changes in serum triglycerides.

"The completion of the ASC40 Phase 2 NASH trial in China demonstrates execution excellence by Gannex and its partner Sagimet," said Dr. Jinzi J. Wu, Founder, Chairman and CEO of Ascletis. "It has given us valuable experience and knowledge for Gannex to move forward with all of our NASH clinical programs."

About ASC40

ASC40 (known as TVB-2640 outside of China) is an orally bioavailable, potentially first-in-class FASN inhibitor. FASN is a key enzyme in the de novo lipogenesis (DNL) pathway that is responsible for the synthesis of excess fat and activation of fibrogenic and inflammatory mechanisms in the liver of patients with NASH. ASC40 targets these key drivers of NASH. Sagimet announced in June 2020 initial results of a randomized, placebo-controlled Phase 2 trial, FASCINATE-1, which evaluated the impact of TVB-2640 in 99 patients with NASH in the United States. Sagimet has demonstrated in preclinical models that blocking FASN not only reduces liver fat, but directly reduces fibrosis and inflammation – addressing three major drivers of NASH.

StephenW

FASN抑制剂ASC40在中国NASH患者队列中显示出阳性的2期临床研究结果

新闻提供者
Ascletis Pharma Inc.

美国东部时间2021年3月8日，美国东部时间19:30
分享这篇文章

    口服FASN抑制剂ASC40可有效降低肝脏脂肪，缓解率达50％
    在美国队列中观察到的肝脏炎症生物标志物的持续改善

美通社-PR Newswire / 2021年3月8日，中国上海和加利福尼亚州圣马特奥市-Ascletis Pharma Inc.（HKEX：1672）的全资子公司Gannex Pharma Co.，Ltd.和Sagimet Biosciences Inc.今天共同宣布一项口服，每日一次的脂肪酸合酶（FASN）抑制剂ASC40（在中国以外被称为TVB-2640）的2期随机，安慰剂对照临床试验的中国队列研究获得了积极的阳性结果，该试验被评估为一种潜在的治疗方法用于非酒精性脂肪性肝炎（NASH）。初步数据显示，ASC40显着降低了肝脏脂肪，这是该试验的主要疗效终点，缓解率为50％（患者降低≥30％）。参与者还显示出与炎症相关的肝酶ALT的强劲改善。来自中国队列的这些数据与之前在2020年11月的AASLD肝病会议上报告的美国队列的数据一致。

杭州师范大学附属医院副院长，脂肪肝副主任史俊平博士说：“我很高兴中国大陆的第二期NASH第二期试验如期完成，并获得了积极的数据。”中华医学会肝病学分会酒精性肝病学组，中国ASC40（TVB-2640）2期试验的主要研究者。 “根据第二阶段的积极数据，我们为中国的2b / 3 NASH阶段试验选择了剂量。”

这项2期临床试验的中国队列评估了30例NASH患者的口服，每日一次剂量的50 mg ASC40或匹配安慰剂的安全性和有效性，为期12周。通过磁共振成像-质子密度脂肪分数（MRI-PDFF）测量，试验参与者必须在基线时具有至少8％的肝脂肪，并需要在肝活检或代谢综合征特征上从F1至F3期肝纤维化的证据。研究表明，ASC40组的肝脏脂肪相对减少了28.2％，而安慰剂组的肝脏脂肪减少了11.1％。 ASC40还显示ALT统计学上显着下降29.8％（p = 0.0499）（在第12周平均下降33 U / L），这表明肝脏炎症有所减轻。在63％的ASC40患者中，ALT降低了17 U / L或更高，这已表明与NASH患者的肝活检反应相关。

ASC40具有良好的耐受性，无严重不良事件。所有治疗的紧急不良事件均为1级或2级，并且血清甘油三酯没有统计学上的显着变化。

Ascletis创始人，董事长兼首席执行官Wu Jinzi J. Wu表示：“ ASC40第二阶段NASH试验在中国的完成证明了Gannex及其合作伙伴Sagimet的出色执行能力。” “它为Gannex推进了我们所有的NASH临床计划提供了宝贵的经验和知识。”

关于ASC40

ASC40（在中国以外被称为TVB-2640）是一种口服生物可用的潜在的一流FASN抑制剂。 FASN是新生脂肪形成（DNL）途径中的关键酶，负责在NASH患者的肝脏中合成多余的脂肪以及激活肝纤维化和炎症机制。 ASC40针对NASH的这些主要驱动因素。 Sagimet于2020年6月宣布了一项随机，安慰剂对照的2期临床试验FASCINATE-1的初步结果，该试验评估了TVB-2640对美国99例NASH患者的影响。 Sagimet在临床前模型中证明，阻断FASN不仅可以减少肝脏脂肪，而且可以直接减少纤维化和炎症-解决了NASH的三个主要驱动因素。