Reuters Health Information: Obeticholic acid promising against NASH liver damage
Obeticholic acid promising against NASH liver damage
Last Updated: 2014-11-24
By David Douglas
NEW YORK (Reuters Health) - Obeticholic acid, a farnesoid X
nuclear receptor ligand (FXR), shows clear benefit in some
patients with non-cirrhotic, non-alcoholic steatohepatitis
"FXR agonists are part of a whole set of new compounds,
which are 'smart' anti-NASH drugs since their mechanisms of
action target critical predisposing conditions and pathways of
liver injury in NASH," said Dr. Brent A. Neuschwander-Tetri of
Saint Louis University School of Medicine in St. Louis,
"Obeticholic acid, the most advanced agent in this class,
has shown clear histological efficacy, across the spectrum of
histological lesions," he told Reuters Health by email. "The
improvement in fibrosis is unprecedented for a relatively small
trial and is therefore promising."
The findings were published online November 7 in The Lancet
to coincide with a presentation at The American Association for
the Study of Liver Diseases' meeting in Boston.
Dr. Neuschwander-Tetri and colleagues note in their report
that obeticholic acid is a potent activator of the FXR receptor
that reduces liver fat and fibrosis in animal models of fatty
To investigate further, the researchers randomized 283
patients to obeticholic acid given orally (25 mg daily) or
Intention-to-treat analysis based on 219 patients eligible
for a 72-week biopsy showed that 50 of 110 (45%) patients on
active treatment had improved liver histology compared to 21% of
109 patients in the placebo group (p=0.0002).
However, 33 (23%) of 141 patients in the obeticholic acid
developed pruritus compared to nine (6%) of 142 in the placebo
group. This led to the use of antipruritic medications or short
periods of withholding treatment in some patients, and treatment
discontinuation in one patient.
Also, serum cholesterol concentrations increased more in the
obeticholic acid patients than in the placebo group.
Overall, said Dr. Neuschwander-Tetri, the findings "validate
this method-of-action specific therapy for NASH. The lipid
changes need to be studied in detail to understand if they are
linked to cardiovascular risk and if they can be mitigated by
simple, additional interventions."
Dr. Vlad Ratziu, author of an accompanying editorial, told
Reuters Health by email that "Lifestyle modification defined as
healthy eating habits and regular exercise remains the primary
recommendation for patients with NASH. It is unlikely that any
one medication will work for everybody with NASH."
However, added Dr. Ratziu of the Université Pierre et Marie
Curie in Paris, "Obeticholic acid was clearly beneficial in some
patients with NASH in (this) trial."
"Further studies," he concluded, "are needed to determine
who might benefit the most. Further studies are also needed to
determine the significance of the increased cholesterol levels
and if these can be managed with statins."
The trial was partly supported by Intercept Pharmaceuticals.
SOURCE: http://bit.ly/1tpS06x and http://bit.ly/1yMhHTq