Q&A: BIO89-100 reduces spleen volume, liver fat in NASH
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BIO89-100, a long-acting glycopegylated fibroblast growth factor 21 analogue, decreased spleen volume that correlated with reduced liver fat, liver fat volume and PRO-C3 levels among patients with nonalcoholic steatohepatitis, data show.
Aimed to investigate the effect of BIO89-100 (89bio) on spleen volume, researchers analyzed 20 patients (mean age, 47.6 years) with biopsy-confirmed NASH and liver fat greater than 10% dosed with BIO89-100 (27 mg: n = 8; 36 mg: n = 8) or placebo (n = 4) for 12 weeks. They assessed spleen volume by MRI at baseline and day 50. They observed a reduction of spleen volume among patients treated with BIO89-100 but not those treated with placebo; reduction in spleen volume correlated with the percentage reduction in liver fat (r = 0.58), liver fat volume (r = 0.59) and Pro-C3 (r = 0.41).
Healio Gastroenterology spoke with study author Rohit Loomba, MD, MHSc, professor of medicine in the division of gastroenterology and adjunct professor in the division of epidemiology at the University of California, San Diego, about the important takeaways, how these results inform treatment going forward and the advice he gives for clinicians treating this subset of patients with NASH.
Healio: Why did your team undertake this investigation?
Loomba: BIO89-100 is being developed and investigated for the treatment of NASH; NASH is a chronic, progressive type of fatty liver disease for which there is currently no approved treatments. Millions of Americans are living with NASH, and it is estimated that the rates will only continue to increase, so research for potential new treatment options is critical.
The data being presented at AASLD is a post hoc analysis of the phase 1b/2a proof-of-concept study evaluating BIO89-100 in patients with NASH. The subanalysis that assessed the correlation between liver fat and spleen volume demonstrated that treatment with BIO89-100 reduced spleen volume by an average of 11.8% in patients with NASH. These are novel findings and something we found interesting to investigate, because prior to this study, correlations between increased spleen volume and improvements in NASH had not been systematically evaluated.
Healio: What is the most important take-home message?
Loomba: The data presented show that increased liver fat and inflammation may lead to subclinical worsening of portal blood flow, which then leads to increased spleen volume in NASH patients without advanced fibrosis. This subanalysis demonstrated that BIO89-100 was able to reduce spleen volume compared to placebo, which also correlated with improvement in liver fat and liver volume. Therefore, portal flow may be improved with treatment that significantly reduces liver fat.
Healio: How do these results inform NASH management going forward?
Loomba: These findings continue to highlight the promising clinical profile of BIO89-100 and its potential to be an optimal treatment for NASH patients.
Healio: What additional research, if any, is needed?
Loomba: The mechanism underlying decrease in spleen volume should continue to be explored and may involve more than an effect on liver fat. Additionally, the role of spleen volume measurement as a noninvasive tool for assessment of portal pressure and the clinical significance of subclinical increase in portal pressure in patients with NASH should be investigated further.
BIO89-100 has also advanced into an ongoing phase 2b clinical trial (ENLIVEN), evaluating the therapy for the treatment of patients with fibrosis stage 2 or 3 NASH.
Healio: What advice would you give to clinicians treating this subgroup of patients?
Loomba: There are currently no approved therapies to treat patients with NASH. Effective, safe and tolerable therapies are needed to treat this chronic and progressive disease. Researchers across the globe are working tirelessly to find new and innovative options.
These findings today show us that we still have so much more to learn and understand about fatty liver disease, but we are optimistic for the future as research continues and more data is generated.
Perspective
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Jamile’ Wakim-Fleming, MD, FACG, FAASLD
NASH affects about 5% of the U.S. population and its prevalence is on the rise. While no FDA approved drugs exist for NASH, several drugs are being investigated.
One of these drugs is B1089-100 which is a long-acting glycol-pegylated fibroblast growth factor 21 analogue. It has been studied in phase 1b/2a proof-of-concept pilot trial of 20 patients with NASH by liver biopsy or by MRE. Results were reported at the Endocrine Society's Annual Meeting in 2021 and at The Liver Meeting in November 2021.
Due to its encouraging results, B1089-100 will be evaluated in phase 2b Enliven trial soon.
In phase 1b/2a trial, B1089-100 has shown to significantly reduce liver fat at 13 weeks along with liver volume reduction and a concurrent reduction in triglycerides and liver enzymes. Researchers also observed a reduction in spleen volume on MRE by 11% which correlated with liver volume reduction and liver fat reduction.
The implication of these findings is that reduction of spleen volume indicates reduction in portal pressure associated with portal hypertension in NASH patients.
Large spleen volume or splenomegaly represents advanced liver disease and portal hypertension. It is associated with sequestration of platelets in the spleen and thrombocytopenia, which contributes to the coagulability observed in portal hypertensive patients with NASH.
Currently there is no effective or widely used treatment for thrombocytopenia nor is there an effective treatment for fatty liver disease. Could B1089-100 be the answer to resolving both issues at the same time?
The hope is that larger trials would follow this pilot study to show reduction of fat in NASH as well as reduction in fibrosis and improvement in the level of thrombocytopenia without incurring significant side effects. We will eagerly await those trials.
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Loomba R, et al. Treatment with BIO89-100 led to decreased spleen volume that was correlated with relative change in liver fat volume and PRO-C3 level in a phase 1b/2a, placebo-controlled, double-blind, NASH proof of concept (POC) study. Presented at: The Liver Meeting Digital Experience; Nov. 12-15, 2021 (virtual meeting).
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