Alnylam 和 Regeneron 在产生疗效迹象后进入基因 NASH 治疗的 2 期

StephenW

Alnylam 和 Regeneron 在产生疗效迹象后进入基因 NASH 治疗的 2 期试验
尼克·保罗·泰勒
2022 年 9 月 15 日 08:09
Regeneron PharmaceuticalsAlnylam非酒精性脂肪性肝炎（NASH）基因沉默
戴手套的手用拼图拼凑出一个肝脏
Regeneron 上个月在 ClinicalTrials.gov 上注册了一项 2 期研究的主要方案。 （盖蒂图片社/阿克萨比尔）

Alnylam 和 Regeneron 已经在他们的 RNAi 非酒精性脂肪性肝炎（ NASH ）项目上大放异彩，概述了在产生早期疗效证据后启动候选药物 2 期临床试验的计划。

候选药物 ALN-HSD 建立在 Regeneron 将 HSD17B13 中的功能丧失变异体与降低慢性肝病和从脂肪变性进展为脂肪性肝炎的风险联系起来的基础上。凭借这一洞察力，Alnylam 部署了其技术来开发一种皮下给药的 RNAi 治疗药物，该治疗药物有可能打开潜在的巨大但迄今为止难以破解的 NASH 治疗市场。

Alnylam 于 2020 年开始测试候选人在健康参与者以及后来在 NASH 患者中的表现。数据现在已经成熟到合作伙伴有证据为进一步发展开绿灯的程度。

在 NASH 患者的前两个​​剂量组中的 20 名受试者中，合作者看到了“稳健”的靶点敲低，令人鼓舞的是该分子按预期工作，以及肝酶和活检衍生的非酒精性脂肪肝疾病活动评分低于比四人对照组的 6 个月。该研究的终点没有统计学意义。
有关的
Regeneron 和 Alnylam 将在发现交易中与 NASH 展开竞争

虽然公众必须等到即将召开的医学会议才能查看数据，但 Alnylam 和 Regeneron 已经看到了足够多的情况，可以开始准备进入第二阶段。试验计划在今年年底开始。

Regeneron 上个月在 ClinicalTrials.gov 上注册了一项 2 期研究的主要方案。该试验包括两项研究，这两项研究都将测试两种剂量，并使用第 52 周连续定量肝纤维化的变化作为主要终点。 ClinicalTrials.gov 列出了 300 名受试者的估计入学人数。

ALN-HSD 的工作正在与 Alnylam-Regeneron 交易涵盖的其他 NASH 项目一起推进。以 PNPLA3 和 CIDEB 为靶点的疗法正在走向首次人体研究，为这对组合提供了一系列潜在的肝病治疗方法。

StephenW

Alnylam, Regeneron hit go on phase 2 trial of genetic NASH therapy after generating signs of efficacy
By Nick Paul Taylor
Sep 15, 2022 08:09am
Regeneron PharmaceuticalsAlnylamnonalcoholic steatohepatitis (NASH)gene silencing
Gloved hands putting together a liver out of puzzle pieces
Regeneron registered a master protocol for a phase 2 study on ClinicalTrials.gov last month. (Getty Images/Aksabir)

Alnylam and Regeneron have hit the gas on their RNAi nonalcoholic steatohepatitis (NASH) program, outlining plans to kick off a phase 2 clinical trial of the drug candidate after generating early evidence of efficacy.  

The candidate, ALN-HSD, is built on Regeneron’s linking of a loss-of-function variant in HSD17B13 to a reduced risk of chronic liver disease and progression from steatosis to steatohepatitis. Equipped with the insight, Alnylam deployed its technologies to develop a subcutaneously administered RNAi therapeutic with the potential to unlock the potentially large, but to date hard to crack, market for NASH therapies.

Alnylam began testing how the candidate performs in healthy participants and, later, in NASH patients in 2020. The data have now matured to the point that the partners have the evidence to greenlight further development.

Across 20 subjects in the first two dose cohorts of NASH patients, the collaborators saw “robust” target knockdown, offering encouragement that the molecule works as expected, as well as liver enzymes and biopsy-derived nonalcoholic fatty liver disease activity scores that were lower over six months than in the four-participant control arm. The study wasn’t powered for statistical significance on the endpoints.
Related
Regeneron, Alnylam to take on NASH in discovery deal

While the public will have to wait until an upcoming medical meeting to get a look at the data, Alnylam and Regeneron have seen enough to start preparing to move into phase 2. A trial is scheduled to start toward the end of the year.

Regeneron registered a master protocol for a phase 2 study on ClinicalTrials.gov last month. The trial features two studies, both of which will test two doses and use change in continuous quantitative liver fibrosis at Week 52 as their primary endpoint. ClinicalTrials.gov lists the estimated enrollment at 300 subjects.

Work on ALN-HSD is advancing alongside other NASH programs covered by the Alnylam-Regeneron deal. PNPLA3- and CIDEB-targeting therapeutics are moving toward first-in-human studies, giving the pair a portfolio of potential treatments for the liver disease.