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Phase II trials and stem cell therapies

Read time: 10 mins
Last updated:2nd Sep 2020
Published:2nd Sep 2020
What drug therapies on the horizon for NASH? Discover range of treatments currently in phase II trials and the trials that didn’t make it to phase III. Also learn about the potential for stem cell therapies in treating NASH.

There are more than a dozen or so treatments in Phase II trials, including agonists for PPAR and farnesoid X receptors, such as Enanta’s EDP 305. Enanta plans to start a further Phase III trial ARGON-2 in NASH in early Q2 2020 and start a Phase I study of EDP 297 as a follow up FXR agonist. Meanwhile Novo Nordisk has decided to test diabetes drug Victoza (liraglutide), or a longer-acting version semaglutide, in fatty liver disease in the phase II LEAN study, after a small study in NASH patients showed that Victoza could deliver improvements. Overweight NASH patients in the LEAN trial showed improvements in liver histology and little worsening of fibrosis. Commentators said larger trials are needed to determine that the drug causes the loss of NASH and not the reduction in obesity.

Gilead Sciences has also shown plenty of interest in the field, paying millions to purchase FXR agonists PX 102 / 104 from Phenex Pharmaceuticals and an acetyl-CoA carboxylase (ACC) inhibitor from Nimbus Therapeutics. Gilead’s GS 9674 (cilofexor) and GS 0976 (firsocostat) in the ATLAS trial showed no significant improvements in liver fibrosis without worsening of NASH but did show improvements in “multiple response measures” of fibrosis and liver function. The combination did not reduce scarring. Also, in phase II trials is the anti-inflammatory MN 001 (tipelukast) from Medici Nova. The Phase II trial of MN 001 was terminated in April 2019 as an interim review showed a significant reduction in triglycerides. The focus is on NASH patients with hypertriglyceridemia.

Stem cell therapies and trials in trouble

Stem cell therapies are under investigation too. In a phase I/IIa trial in 19 patients with chronic liver disease, HepaStem, a stem cell therapy developed by Promethera has improved symptoms such as jaundice.


Figure 1 Liver-derived progenitor cells are injected into the portal vein. These cells then differentiate into functional liver cells (Adapted from Dutton2).

The first clinical trials for Promethera’s NASH cell therapy are expected to begin within a year1.

A number of trials have also run into trouble. A 144-patient phase II trial of antisense gene therapy drug AKCEA-ANGPTL3-LRx, from Ionis’s subsidiary Akcea, in patients with NAFLD, type 2 diabetes and hypertriglyceridemia reported in January 2020 showing significantly reduced triglycerides and a favourable safety profile but no reduction in liver fat. The rights to the drug were sold to Pfizer for $250 million. Trials of Shire’s SHP 626 (volixibat) have been discontinued after studies showed no clear benefits in patients with NASH. Gilead’s injectable anti LOXL2 monoclonal antibody GS 6624 (simtuzumab) has also been cancelled after three no effect trials Conatus has terminated the emricasan programme and its collaboration with Novartis was cancelled.


  1. Pinxteren J, Deltour E, Scholasse J, Manzoni F. Challenges in developing an off-the-shelf cell therapy for ACLF and NASH. Cytotherapy. 2019;21(5):S87.
  2. Dutton G. Tackling diverse liver diseases with a versatile cell therapy. Genetic Engineering & Biotechnology News. 2016;36(18). Accessed 29 July 2020.

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