Regeneron and Alnylam Report Promising Data from Ongoing Phase 1 Study of ALN-HSD in NASH Patients and Healthy Volunteers
Target knockdown and safety results support continued clinical development
Detailed results to be presented at an upcoming medical congress
After single-dose evaluation in healthy adult volunteers (Part A), multiple doses of ALN-HSD are being studied in adult patients with NASH (Part B). Patients in the first two Part B cohorts (200 and 400 mg quarterly) have completed at least 6 months on the study; remaining cohorts are exploring a lower dose or a later biopsy time point. In the first two Part B cohorts, ALN-HSD was associated with robust target knockdown and numerically lower liver enzymes and biopsy-derived nonalcoholic fatty liver disease (NAFLD) Activity Score (NAS)* over six months in patients receiving ALN-HSD (N=20) relative to placebo (N=4). The study was not powered to achieve statistical significance on these endpoints, and the primary outcome measure is frequency of adverse events. ALN-HSD has exhibited an encouraging safety and tolerability profile to date; the most common treatment-emergent adverse event in healthy subjects treated with ALN-HSD (N=44) was injection site reaction in five patients; all injection site reactions were mild in severity. No treatment-related serious adverse events have been reported in either healthy volunteers or patients with NASH to date. Based on these results, the companies plan to initiate a Phase 2 study in adult patients with NASH in late 2022.
"We are excited to share these initial results, indicating what we believe to be a favorable profile for ALN-HSD and supporting continued clinical development of this investigational medicine, particularly given the significant prevalence and unmet need in NASH – a progressive liver disease and a leading cause of liver transplant," said
"The Regeneron and
* The NAFLD Activity Score (NAS) is a widely accepted scoring system developed by the NASH Clinical Research Network for use in clinical trials. The score is based on histological assessment of liver biopsies and is comprised of a sum of steatosis, ballooning, and lobular inflammation component scores.
About the Phase 1 Study Design
The Phase 1 trial is a randomized, double-blind, placebo-controlled, multi-center, single-ascending dose (SAD) and multiple-dose (MD) study designed to evaluate the safety, tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) effects of ALN-HSD in healthy adult subjects and adult patients with NASH. The primary endpoint of the study is the frequency of adverse events. The study was conducted in two parts. Part A enrolled 58 healthy adult subjects randomized 3:1 to receive a single ascending dose of 25, 100, 200, 400, or 800 mg of ALN-HSD or placebo; Part A of the study is complete. Part B enrolled 45 patients with NASH randomized 4:1 to receive two doses of 25, 200, or 400 mg of ALN-HSD or placebo, quarterly. Patients in the first two cohorts (200 and 400 mg) have completed at least 6 months on the study; remaining cohorts are exploring a lower dose or a later biopsy time point. Secondary and exploratory endpoints of the study include the characterization of plasma and urine PK of ALN-HSD and the evaluation of the drug PD effect.
ALN-HSD is an investigational, subcutaneously administered RNAi therapeutic targeting HSD17B13 for the treatment of NASH. It is being developed in collaboration with Regeneron following their identification of a loss-of-function variant in HSD17B13 that is associated with a reduced risk of chronic liver disease and progression from steatosis to steatohepatitis1. ALN-HSD utilizes
Nonalcoholic steatohepatitis (NASH) is a highly prevalent chronic liver disease in which inflammation and liver cell injury are caused by accumulation of hepatic fat. NASH is a subset of a group of conditions called nonalcoholic fatty liver disease (NAFLD) that can lead to progressive fibrosis, cirrhosis, and hepatocellular carcinoma. Comorbidities include obesity, metabolic syndrome, and type 2 diabetes. Approximately 16 million people in the US live with NASH, with prevalence of the disease increasing due to rising rates of obesity. NASH is projected to be the leading indication for liver transplants in developed countries within the next 10 years. There are currently no approved medical therapies for NASH.
RNAi (RNA interference) is a natural cellular process of gene silencing that represents one of the most promising and rapidly advancing frontiers in biology and drug development today. Its discovery has been heralded as "a major scientific breakthrough that happens once every decade or so," and was recognized with the award of the 2006 Nobel Prize for Physiology or Medicine. By harnessing the natural biological process of RNAi occurring in our cells, a new class of medicines, known as RNAi therapeutics, is now a reality. Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise
Regeneron (NASDAQ: REGN) is a leading biotechnology company that invents, develops and commercializes life-transforming medicines for people with serious diseases. Founded and led for nearly 35 years by physician-scientists, our unique ability to repeatedly and consistently translate science into medicine has led to nine FDA-approved treatments and numerous product candidates in development, almost all of which were homegrown in our laboratories. Our medicines and pipeline are designed to help patients with eye diseases, allergic and inflammatory diseases, cancer, cardiovascular and metabolic diseases, pain, hematologic conditions, infectious diseases and rare diseases.
Regeneron is accelerating and improving the traditional drug development process through our proprietary VelociSuite® technologies, such as VelocImmune®, which uses unique genetically humanized mice to produce optimized fully human antibodies and bispecific antibodies, and through ambitious research initiatives such as the Regeneron Genetics Center, which is conducting one of the largest genetics sequencing efforts in the world.
For more information, please visit www.Regeneron.com or follow @Regeneron on Twitter.
Alnylam Forward Looking Statements
Various statements in this release concerning
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- Abul-Husn NS., et al., 2018,
The New England Journal of Medicine, "A Protein-Truncating HSD17B13 Variant and Protection from Chronic Liver Disease", 378:1096-1106.
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