Clinical efficacy data for Madrigal Therapeutics’ Phase II NASH therapeutic, MCL-3196, which was presented at the 2018 International Liver Congress (ILC) in Paris, France, demonstrated the investigational drug met its primary endpoint of liver fat reduction versus a placebo.
GlobalData believes it is now well-positioned to move into Phase III trials, despite Phase II trials still ongoing.
Madrigal’s MCL-3196, a first-in-class thyroid hormone receptor β agonist, is in development for the treatment of NASH, a disease caused by fatty deposits in the liver that currently has very limited therapeutic options despite a high prevalence in developed countries. The drug has found to exhibit selective liver uptake, where it stimulates metabolic activity, resulting in a reduction in liver fats such as cholesterol, triglycerides, and lipoproteins. By selectively targeting liver cells over other body cells, the risk of adverse events (AEs) occurring due to stimulated metabolic activity in other areas of the body is reduced.
MCL-3196 is currently under evaluation in a double blind, placebo controlled Phase II trial enrolling 125 NASH patients. Those assigned to the study arm receive an 80mg dose of MCL-3196, which could be increased to a 100mg dose at Week 4 based on exposure. Patients receive treatment for a total of 36 weeks, with the primary endpoint being the relative liver fat reduction as measured by MRI at Week 12. Secondary endpoints included liver fat reduction as measured by MRI and liver biopsy at Week 36, as well as other measures of liver health relevant to NASH, such as fibrosis.
Data from the primary endpoint collected at Week 12 of the study was presented at the ILC2. The drug was found to have met its primary endpoint, with an average relative reduction in liver fat of 36.6% in the study arm versus 9.6% in the placebo arm. Those who had been switched to the higher dosing regimen of MCL-3196 were found to have an even greater response, with an average relative reduction of 42.0%. Overall, 60.3% of those receiving MCL-3196 experienced greater than 30% reduction in liver fat, versus 18.4% in the placebo group. MCL-3196 was statistically superior to the placebo group using both of these measures (p<0.0001).
So far, only limited safety data from the trial have been presented, due to the fact that the trial is still ongoing, and as such safety data has not been fully collected. However, preliminary safety data from the first 12 weeks of the trial suggest that MGL-3196 is well-tolerated, with most AEs considered mild. Three serious AEs (SAEs) have been documented so far in the study, but all have been considered unrelated to the study drug.
These positive Phase II trial results place Madrigal in a strong position moving forward with clinical development. As a result, Madrigal has announced its intention to initiate Phase III trials for the drug in 2018. By treating the cause of NASH, rather than the symptoms, GlobalData believes that the drug has significant potential as part of the hepatologists’ arsenal for treating NASH. However, it will be important to see if drugs like MGL-3196 have a suitable role in the long-term management of NASH, and it will likely remain important for patients to make lifestyle changes alongside therapeutic treatment in order to effectively control the disease.
For more insight and data, visit the GlobalData Report Store – Drug Development Technology is part of GlobalData Plc.
GlobalData (2017). OpportunityAnalyzer: NASH – Opportunity Analysis and Forecasts to 2026, May 2017, GDHC068POA. https://www.globaldata.com/store/report/gdhc068poa–opportunityanalyzer-nash-opportunity-analysis-and-forecasts-to-2026/