Madrigal Pharmaceuticals, a Pennsylvania-based drug company, announced Monday more positive safety data for a medicine it's been developing to treat a common form of liver disease.
In a late-stage study of almost 1,000 patients, Madrigal said its medicine, called resmetirom, appeared safe and well-tolerated across both the 80 milligram and 100 milligram doses that were tested. Most side effects observed after treatment were mild to moderate, and the frequency at which they occurred was similar between the study's drug and placebo arms. Compared to the control group, patients who received resmetirom more often experienced mild diarrhea or increased bowel movements at the start of treatment.
Madrigal's study enrolled patients presumed to have NASH, or non-alcoholic steatohepatitis, a liver disease caused by a buildup of fat in the organ. In addition to safety, the trial looked at measures of liver health, and found that resmetirom offered significant lowering of liver fat as well as reductions in certain "bad" fats like triglycerides and LDL cholesterol.
A second trial evaluating the drug in patients confirmed to have NASH is ongoing, with initial results expected later this year, sometime between July and the end of September. Still, the late-stage data seen thus far "support our conviction that resmetirom has the potential to be the first medication approved for the treatment of patients with NASH and liver fibrosis," said Paul Friedman, Madrigal's CEO, in a statement Monday. (The company had previously disclosed positive data from an open-label segment of its study focused on the higher dose of resmetirom.)
The fresh results seem to have buoyed Madrigal investors, too. Company shares began trading Monday at a little over $59 apiece, up roughly 5% from Friday.
NASH has become a leading cause of liver disease in the U.S., affecting millions of patients by some estimates. If NASH is left unchecked, patients can develop liver tissue scarring and cirrhosis, and may eventually need a transplant.
Wall Street sees a multibillion-dollar opportunity in NASH drugs. But despite their best efforts, pharmaceutical companies haven't been able to crack the complicated biology of the disease. In the past couple years, many of the most closely watched experimental drugs for NASH have failed key clinical trials.
Resmetirom is one of the few NASH drugs that has advanced to late-stage testing. It's meant to promote the activity of thyroid hormone — a molecule which is important for liver function but can be impaired when the organ is inflamed.
Specifically, Madrigal's drug is designed to act on a protein called thyroid hormone receptor-beta while avoiding the related thyroid hormone receptor-alpha, which regulates how the molecule interacts with other parts of the body, like the heart. That design is important, according to Jefferies analyst Akash Tewari, because historically, drugs that mimic the effects of thyroid hormone haven't been so selective. And as a result, they've been associated with adverse events related to the heart, bones and liver.
To Thomas Smith, an analyst at SVB Leerink, the data released Monday are "incrementally validating for the established profile of the drug on both safety and efficacy."
But others aren't so sold, especially in light of the many setbacks NASH drugmakers have run into. For instance, Steven Seedhouse of the investment bank Raymond James noted how Madrigal didn't release data on liver function tests, fibrosis markers, thyroid hormone tests or weight loss, which are all crucial to understanding resmetirom's potential benefits.
"Overall, the Phase 3 data affirm our conviction that resmetirom is not a good drug for NASH, which will likely also be evidenced by the upcoming [NASH study readout]," Seedhouse wrote in a note to clients Monday.