Enyo Pharma’s liver disease drug reduced liver fat and boosted kidney health during a mid-stage clinical trial, meeting its main and secondary goals while supporting the design of next stage pivotal studies.
Vonafexor, also known as EYP001, is being trialed in patients with nonalcoholic steato-hepatitis (NASH), a liver disease that causes excess fat to build up in the liver, leading to damage or even failure. The phase 2a study, called Livify, featured 96 patients who received either vonafexor or placebo.
The therapy reduced liver fat by 5% or greater in 58% of patients, compared with 22% seen in the placebo group. Vonafexor also reduced other important biomarkers that can signal damage to the organ and improved kidney function, while patients on placebo saw a deterioration of kidney function.
Enyo said the drug also reduced body weight, waist circumference and waist-to-height ratio, which can all provide metabolic and cardio-vascular morbidity benefits.
“The additional positive impact on renal function is very interesting and is a potential differentiator in this class of drugs to treat NASH,” said the study’s principal investigator, Prof. Stephen Harrison, medical director of Pinnacle Clinical Research. NASH patients typically have other conditions like diabetes that can impact kidney function.
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NASH is a highly sought-after indication, with dozens of companies—big and small—trying to crack the market. Enyo will go up against Gilead and Novo Nordisk, which are working on a cocktail through a fatty liver disease R&D pact. Terns Pharmaceuticals, backed by Eli Lilly, is pushing two NASH treatments into a phase 2a study in the first half of 2022.
But several companies have reported failures deep into clinical testing, such as Genfit and NGM Biopharmaceuticals. NASH could bring in billions for any companies that get across the finish line. Some analysts predict tens of billions of dollars in sales per year, though the rocky path to be the first to approval has scaled back these forecasts.
One challenging aspect of NASH is that diagnosis is typically performed using invasive liver biopsies. Enyo said the phase 2a results were detected via non-invasive tests. The reduction of liver fat was identified using an MRI.
Enyo did not report full data for adverse events but did say that patients experienced itchiness—a stubborn side effect of many clinical-stage NASH drugs of this class. The cases were generally mild and less than 10% of patients dropped out because of this side effect, according to the company's release.
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Enyo CEO Jacky Vonderscher, Ph.D., said the results support the development of pivotal regulatory studies for vonafexor. The company plans to trial the drug in combination with other treatments “to maximize the benefit of such treatments for NASH patients,” with a combo approach currently being favored by other biopharmas, given the mixed results when drugs are used on their own.
Further results from the study will be released at future medical meetings.
The clinical trial was supported by €40 million ($46.9 million) raised by Enyo in a June 2018 series B round. The funds supported two clinical trials for vonafexor in chronic hepatitis B and NASH.