On a quest to expand the eligible patient pool for its fast-growing liver disease drug Rezdiffra, Madrigal Pharmaceuticals has unveiled two-year biomarker results from an open-label study in those with compensated metabolic dysfunction-associated steatohepatitis (MASH) cirrhosis.
Rezdiffra made headlines last year as the first drug cleared to treat MASH, with the FDA specifically clearing the drug in patients with stages F2 and F3 non-cirrhotic MASH.
As the launch gains steam in that patient population, Madrigal remains focused in its effort to reach the compensated MASH cirrhosis (F4c) patient population. An approval in the setting represents “a key pillar of our long-term" strategy, CEO Bill Sibold said on an investor call earlier this month, and could double the drug's market opportunity.
Now, Madrigal has announced two-year biomarker results from this patient group at the European Association for the Study of the Liver Congress in Amsterdam.
Patients in the open-label F4c arm of the Maestro-NAFLD-1 trial achieved “significant improvements” from baseline in liver stiffness, liver fat, fibrosis biomarkers, liver volume and risk scores for clinically significant portal hypertension (CSPH), according to Madrigal.
CSPH is a “major consequence” of cirrhosis, or liver scarring, and is linked to "severe” complications, according to the company. MASH patients who progress to cirrhosis are at a much higher risk of liver-related mortality than those who do not, Madrigal explained.
Of patients with CSPH at baseline, 65% who were treated with Rezdiffra moved into lower-risk categories by year two, according to the company.
In a note to clients, Citi analysts described the results as “highly encouraging,” but they cautioned that the “degree of clinical translatability” based on the biomarker results "remains unclear." Definitive outcomes from the ongoing study will still be needed for the company to secure a potential label expansion, the analysts said.
As for Madrigal, the company believes that the new data add “important clinical evidence that supports our confidence in the ongoing, fully enrolled Phase 3 outcomes trial of Rezdiffra in compensated MASH cirrhosis,” Chief Medical Officer David Soergel, M.D., said in a statement.
An estimated 1.5 million patients have been diagnosed with MASH in the U.S., but Madrigal expects that number to grow with increased disease awareness and prevalence.