While there are no marketed drugs for nonalcoholic steatohepatitis (NASH) in the EU or US, most NASH therapies in development primarily focus on treating patients with F2 (moderate fibrosis) or F3 (advanced fibrosis). Of the 33 late-stage pipeline assets in development for NASH, only three focus on decompensated cirrhosis (DC) due to NASH. A further look into the mechanisms of action (MOAs) of each agent reveals that Promethera Biosciences and Cellaion’s HepaStem (heterologous human adult liver progenitor cells) holds the most promise, according to GlobalData.
NASH is a severe form of nonalcoholic fatty liver disease (NAFLD) that can remain undiagnosed for years, given the lack of symptoms experienced during the initial stages. HepaStem is a stem cell therapy consisting of liver-derived mesenchymal stem cells (MSC) that addresses different components of NASH disease progression. It is administered intravenously without the need for immunosuppressants and enters the liver via the bloodstream, where it then targets multiple disease pathways to reduce tissue fibrosis and promote the restoration of liver function by lowering inflammation, deactivating stellate cells, and reducing fibrosis.
Sravani Meka, Senior Immunology Analyst at GlobalData, comments, “While there has been limited data released from the Phase IIb of HepaStem and standard of care (SoC) in patients with acute-on-chronic liver failure (ACLF), ongoing studies for the treatment of ailments including neurological disorders, cardia ischemia, and diabetes have shown the beneficial effects of MSC-based therapies. As such, it is unsurprising that a stem cell therapy is being considered for the treatment of DC due to NASH. Nonetheless, the path to HepaStem’s approval will not be easy given the lack of previous drug data in ACLF patients as well as possible long-term side effects (ex., tumor formation, immune reactions, and therapy failure). Furthermore, it may be difficult to distinguish whether any AEs were caused by NASH or due to treatment complications, as the morbidity and mortality rates are high in this patient segment.”
The three pipeline agents being evaluated for the treatment of NASH patients with DC include HepaStem, BioVie’s BIV201 (continuous infusion terlipressin), and Grifols’ Albutein (albumin-human injection). Albutein appears to be on track to be the first therapeutic approved for DC, with a projected US launch date in Q1 2026. HepaStem is projected to hit the US market in Q1 2027, while BioVie’s BIV201 is anticipated to be marketed in Q4 2028.
Both Albutein and BIV201 are in development for the treatment of ascites (excess fluid in the abdominal cavity) caused by the persistent inflammation of the liver. Although both appear to be beneficial treatments for ascites due to DC, BIV01 may prove to be more effective for the treatment of ascites as it works to limit the underlying cause of disease progression. Clinical research has shown that despite the extensive use of albumin infusions in patients with cirrhosis to improve renal function and facilitate the elimination of ascites, the observed benefits are very modest and limited only to patients with slightly impaired renal function who respond to conventional therapy.
Sravani concludes, “Despite limited data, HepaStem appears to be the most promising agent as it is the only therapeutic that is being investigated with the purpose of restoring liver function and reverse decompensation. However, BIV201 and Albutein may be favorable options as bridge therapies to increase survival time for NASH patients awaiting a liver transplant. Notably, as the NASH market continues to see approvals for agents focusing on cirrhosis improvement and liver regeneration that are indicated for patients in the earlier stages of NASH, the need for a treatment option for DC due to NASH will decrease as fewer patients develop DC. Until that point is reached, it remains to be seen whether or not HepaStem, BIV201, and Albutein will perform and gain approval.”