Dive Brief:
- Wednesday's news that Madrigal Pharmaceuticals, Inc.'s MGL-3196 has hit its primary endpoint in a Phase 2 for non-alcoholic steatohepatitis (NASH) trial shot the company's stock up over 100% during the day, closing more than 88% higher.
- At 12 weeks, MGL-3196 showed statistically significant improvement in the relative decrease in liver fat compared with placebo, as measured by magnetic resonance imaging-estimated proton density fat fraction (MRI-PDFF).
- Significantly more patients treated with MGL-3196 had a clinically relevant liver fat reduction (greater than 30%), and improvements in liver enzymes, low-density lipoprotein cholesterol (LDL-C), triglycerides and lipoprotein compared with placebo. MGL-3196 was well-tolerated with mild and a few moderate adverse events.
Dive Insight:
NASH, which can progress to liver cirrhosis and cancer, is becoming a potential health crisis. NASH affects around 2% to 3% of people in the U.S., and the incidence is increasing as populations become more and more obese. Non-alcoholic fatty liver disease, the precursor of NASH, is even found in children.
There is currently no Food and Drug Administration-approved treatment for NASH, and the astonishing rise in Madrigal Pharmaceuticals, Inc.'s stock demonstrates the potential interest in a therapeutic. MGL-3196, is an oral, once-daily, liver-directed, thyroid hormone receptor β -selective agonist, and according to Madrigal, targets both the metabolic syndrome and fatty liver disease components of NASH.
"We are gratified to see clinical results that strongly suggest MGL-3196 has the potential to provide clinically meaningful improvement of NASH by targeting lipotoxicity and inflammation as well as by reduction of cardiovascular risk by lowering atherogenic lipids. These… continue to suggest that MGL-3196 has the potential to address the root causes of the underlying disease process in NASH," said Paul Friedman, CEO of Madrigal.
Jefferies analyst Michael Yee described Madrigal's data as "intriguing and promising" in a note to investors, saying that the data is good, all the reported measure are "going in the right direction", and confirming that the MRI-PDFF reduction of greater than 30% is increasingly viewed as a surrogate for fibrosis improvement.
"We await 36 week biopsy and safety data to determine its position in the NASH space and competitive potential, Yee added.
Madrigal isn't the only company staging a race to the NASH market. Perhaps closest to the market is Intercept Pharmaceuticals' Ocaliva (obeticholic acid), currently in a Phase 3 trial with a readout due in the first half of 2019. Big pharma Boehringer Ingelheim GmbH is working with Dicerna Pharmaceuticals, Inc. to develop drugs based around RNA interference (RNAi) technology.
It's not an easy area to succeed in though. Gilead Sciences, Inc.'s GS-0976 has generated mixed results, and Galectin Therapeutics, Inc.'s GR-MD-02 failed to meet its primary endpoint in a Phase 2b study, according to data released earlier this month. And Allergan plc's cenicriviroc has shifted its focus onto treating liver fibrosis after it did no better than placebo at treating NASH.