Four years ago, scientists at Regeneron Pharmaceuticals had a discovery to share. By examining DNA sequences and electronic health records from nearly 50,000 people, they found a genetic variant that seemed to confer protection from chronic liver disease.
The finding, published in March 2018 in The New England Journal of Medicine, became the foundation for a partnership between Regeneron and fellow biotechnology company Alnylam Pharmaceuticals to develop a new kind of drug for the liver disease non-alcoholic steatohepatitis, or NASH.
That work now seems to have borne some fruit, as the companies on Thursday said early clinical trial data has encouraged them to plan a mid-stage study they aim to begin later this year.
The data come from a Phase 1 trial Alnylam and Regeneron have been running since late 2020. Divided into two parts, the study first tested the companies’ drug in healthy volunteers, and then in adult patients with NASH, which is caused by the accumulation of liver fat and is thought to be widely prevalent in the U.S.
Treatment led to “numerically lower” liver enzymes as well as lower fatty liver scores over six months than did placebo, although the study was not designed to statistically compare the two groups for efficacy. Twenty participants received the companies’ drug, called ALN-HSD, in one of two doses, while four received placebo.
No serious adverse reactions related to the drug were reported in either the trial’s healthy volunteers or NASH patients, Alnylam and Regeneron said. Among the healthy adults, the most common “treatment-emergent” side effects were mild injection site reactions.
“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,” Kevin Sloan, who leads the drug program for Alnylam, said in a statement.
The companies plan to share detailed data at a future medical meeting, as well more information on the planned study. A new clinical trial listing posted Aug. 29 to a federal database describes a placebo-controlled Phase 2 study testing ALN-HSD in 300 participants.
ALN-HSD is based on a drug-making technology that Alnylam has spent two decades perfecting. Known as RNA interference, or RNAi, the technology allows researchers to design drugs that can “silence” the genetic messenger molecules that tell cells to make proteins.
It’s a powerful and flexible platform that Alnylam has used to develop four approved rare disease drugs, and now hopes to apply to treating more common conditions like NASH, hypertension and Alzheimer’s disease. (An RNAi drug recently approved in the U.S. and sold by Novartis for high cholesterol was invented by Alnylam.)
In the case of ALN-HSD, the drug targets a gene called HSD17B13. Genetic variants that resulted in the loss of the gene’s function were associated in Regeneron’s research with lower levels of certain liver enzymes. Further work established a connection between mutated copies of the gene and lower risk of chronic liver disease, as well as progression from fat buildup in the liver to the inflammation and damage known as steatohepatitis.
Caused by that accumulation of fat, NASH involves a scarring of tissue and, in severe cases, can progress to liver cirrhosis. While estimates of its prevalence vary widely, most agree that millions of people in the U.S. live with NASH. Diagnosis is difficult, however, and can only be done conclusively by a liver biopsy, which is invasive and expensive.
Biotech and pharma companies alike have tried to develop drugs for NASH but most efforts have failed or otherwise fallen short. One company, Intercept Pharmaceuticals, has had success in Phase 3 testing with a NASH drug, but has run into issues getting it approved.
Earlier this week, shares in another biotech, Akero Therapeutics, more than doubled in value after the company reported positive Phase 2 study results.