8 Recent Reports on Treatment, New Trials from International NASH Day

Issue: August 2018

In recognition of the first International NASH Day on June 12, 2018, Healio.com presents several recent reports on the diagnosis and treatment of nonalcoholic steatohepatitis, including several new drug trials that were presented at the recent International Liver Congress in Paris and Digestive Disease Week in Washington, D.C.

Along with details on a recent collaboration to define a NASH outcome consensus and a physician’s call to action to tailor lifestyle interventions for individual patients, the following reports include study outcomes on a cirrhosis inhibitor, a thyroid receptor agonist and potential combination therapy for NASH

Call to action: Tailor lifestyle interventions for NAFLD to patients

Lifestyle interventions such as diet and exercise are a critical part of prevention and treatment of nonalcoholic fatty liver disease and NASH, more so than pharmacotherapy or endoscopic interventions at this moment, according to an expert at Digestive Disease Week 2018.

“My task today is to get everyone reinvigorated about the role of diet and exercise in the treatment of NAFLD and NASH,” Monica Konerman, MD, director of the Michigan Medicine NAFLD Clinic, said during her presentation. “With all of the new trials in pharmacotherapy and the exciting bariatric endoscopic interventions, people don’t tend to get as excited about diet and exercise, but hopefully that will change.” Read more

Multiparametric MRI identifies hallmarks of NASH

Multiparametric magnetic resonance imaging identified and stratified patients with NAFLD and NASH at a population level, according to a study presented at Digestive Disease Week 2018.

“We’re trying to find a noninvasive way to identify these patients at risk for disease progression,” Stephen A. Harrison, MD, medical director of Pinnacle Clinical Research, San Antonio, said during his presentation. The way we estimated this NAFLD and NASH prevalence was using multiparametric MRI, specifically corrected T1 and proton density fat fraction.” Read more

Collaboration launches initiative to develop NASH outcome consensus

The Center for Medical Technology Policy’s Green Park Collaborative, the Forum for Collaborative Research and the Obesity Action Coalition announced the launch of its ‘coreNASH’ initiative, designed to develop a consensus on critical outcomes in NASH clinical research, according to a press release.

The initiative will involve a multi-stakeholder team, including clinicians, patients with NASH, payers, health technology assessment groups, regulators and life sciences companies, who will help establish a consistent and stakeholder-relevant baseline for evaluation of NASH therapies. Read more

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HistoIndex, CymaBay collaborate on phase 2 study of seladelpar for NASH

HistoIndex announced a collaboration with CymaBay to evaluate the efficacy of seladelpar for NASH in a randomized control phase 2b study using HistoIndex’s Genesis 200 multiphoton digital pathology system, according to a press release.

“We are enthusiastic to work with CymaBay, and our passion synchronizes with their dedicated efforts to bring effective NASH therapeutics to patients,” Gideon Ho, PhD, CEO of HistoIndex, said in the release. “I am confident that our imaging technology will allow us to accurately quantify and track changes in fibrosis and relevant NASH characteristics such as steatosis, hepatocyte ballooning and lobular inflammation.” Read more

Conatus completes enrollment in phase 2 trial for NASH cirrhosis inhibitor

Conatus Pharmaceuticals completed enrollment in its ENCORE-PH phase 2 clinical trial for emricasan, an orally-active pan-caspase inhibitor designed to treat NASH-related cirrhosis, according to a press release.

“We look forward to the upcoming series of emricasan clinical trial readouts and the potential opportunity to advance this novel product candidate toward addressing the unmet medical needs of NASH fibrosis and cirrhosis patients,” David T. Hagerty, MD, executive vice president of clinical development at Conatus, said in the release. Read more

Gilead focuses on combination therapy to treat NASH fibrosis

In this exclusive interview from the International Liver Congress 2018, Mani Subramanian, PhD, discusses innovative approaches to treating advanced fibrosis in patients with NASH.

“What is very exciting is the number of programs that are looking at single-agents targeting different aspects of NASH,” Subramanian, senior vice president of liver disease therapeutics at Gilead, told Healio Gastroenterology and Liver Disease. “The results of these studies will be available in the first half of 2019, but the primary endpoint is based on a liver biopsy to show reduction of liver fibrosis with no worsening of the components of NASH.” Read more

Galectin-3 inhibitor improves hepatic ballooning in NASH

GR-MD-02, a novel galectin-3 protein, did not improve hepatic venous pressure gradient in patients with NASH and cirrhosis; however, the inhibitor did significantly improve hepatocyte ballooning, according to a presentation at the International Liver Congress 2018.

“Change in [hepatic venous pressure gradient (HVPG)] associated with GR treatment was not significant in total patient population, but statistically significant in the pre-specified group of mild portal hypertension,” Naga Chalasani, MD, from the Indiana University School of Medicine, said in his presentation. “In patients without varices at baseline, there was a statistically significant difference in the [2 mg/kg] group in the change in HVPG, percentage of responders, and development of new varices.” Read more

Thyroid receptor agonist for 12 weeks reduces hepatic fat in NASH

Twelve weeks of MGL-3196 — an orally active, highly selective thyroid hormone receptor beta-selective agonist — significantly decreased hepatic fat in patients with NASH compared with placebo in a phase 2 trial, according to data presented at the International Liver Congress 2018.

“We know in human NASH, the liver is relatively low in thyroid hormone receptor beta activity, potentially exacerbating mitochondrial dysfunction and lipotoxicity,” Stephen A. Harrison, MD, medical director of Pinnacle Clinical Research, San Antonio, said in his presentation. “It’s been shown in humans that thyroid hormone receptor beta-agonist activity lowers LDL cholesterol, lowers triglycerides, lowers liver fat — predominately through the breakdown of free fatty acids — stimulating mitochondrial biogenesis in the NASH liver.” Read more