Tag Archives: obeticholic acid

FDA Warning for Obeticholic Acid

Posted on by

Obeticholic acid was approved last year as a treatment for primary biliary cholangitis (PBC). Now (9/21/17), the FDA warns of 19 deaths associated with Obeticholic Acid, particularly when the medication has been used at higher than recommended dosing.

Link: FDA Warning on Obeticholic Acid

An excerpt:

Nineteen cases of death were identified, of which eight provided information about the patient’s cause of death. The cause of death was reported to be worsening of PBC disease in seven cases, with cardiovascular disease cited in the other case. Seven of these eight cases described patients with moderate to severe decreased liver function who received Ocaliva 5 mg daily, instead of a dose no greater than 10 mg twice weekly as recommended in the label prescribing information for patients with this extent of decreased liver function.

Will Emerging Therapies for Fatty Liver Disease Be Affordable?

Posted on by

With non-alcoholic steatohepatitis (NASH), there are currently no established medical therapies.  However, several candidate medications look promising. However in recent years, many new medications have come with an impressive price tag and this has led to questions about whether emerging therapies for NASH will be affordable.

A recent article looked at the medication Obeticholic Acid, which was approved for treating primary biliary cholangitis.  It is possible that it will be helpful for NASH.  Yet, its cost , currently, is about $70,000 per year

GIHepNews: Despite clinical promise, obeticholic acid may be too expensive for treating NASH

Here’s an excerpt:

In the 72-week Phase II trial, called FLINT, 273 men and women with NASH were randomly assigned to receive OCA or placebo (Lancet 2015;385:956-965). Liver histology improved in 45% of those receiving OCA versus 21% in those receiving sham therapy (P=0.002). An increased risk for pruritus was the most notable adverse event among patients taking OCA (23% vs. 6% for placebo), according to the researchers. Based on the favorable benefit–risk results of the Phase II study, a Phase III trial is ongoing…

The expected benefit of OCA over lifestyle modifications for all the major long-term outcomes, such as decompensated cirrhosis (10% vs. 9.4%), liver-related mortality (9% vs. 8.1%) and transplant-free survival (72.2% vs. 71.5%), were relatively modest, the researchers reported. Those differences resulted in a cost per quality-adjusted life-year saved of $5.2 million with the assumption that 16% of patients would relapse…

 “If the efficacy compared to placebo is of the same order found in the FLINT trial, the current cost of the drug would be prohibitive in a population-based context,” said Dr. Lavine, who was a co-investigator on the trial.

My take: Given the growing burden of NASH, new effective treatments are needed.  In my view, though, cost-effectiveness has to be a consideration.

Prague Castle

Obeticholic Acid in Primary Biliary Cholangitis

Posted on by

While Primary Biliary Cholangitis (PBC) (previously called primary biliary cirrhosis) is seen mainly in adult hepatology practices, a new treatment may be emerging and this same medication is likely to be considered for several liver conditions.

Reference: F Nevens et al. NEJM 2016; 375: 631-43.

This 12 month, double-blind, placebo-controlled phase 3 “POISE” trial with 217 patients examined the use of obeticholic acid with or without ursodeoxycholic acid.  Surrogate markers of PBC were followed & the treatment groups improved compared to placebo.  However, adverse effects, particularly itching, were more common in the obeticholic acid groups; serious adverse effects were 11-16% in the treatment groups compared with 4% in the placebo group.

Results below:

PBC Rx

My take: It will be nice when important clinical endpoints can be assessed for this therapy like progression to cirrhosis.  For now, the cost of this treatment is ~$70,000 yearly.

Related blog post:

Breakthrough for Fatty Liver Disease? | gutsandgrowth

NASH Update -September 2015

Posted on by

Briefly noted:

Obeticholic acid, a Farnesoid X Receptor Ligand, is being studied as a potential agent in nonalcoholic steatohepatitis (NASH).  According to a recent study (Lancet 2015; 385: 956-65), patients assigned to receive obeticholic acid were more likely to have improved liver histology compared with placebo (50/110 [45%] compared with 23/109 [21%]).  The  obeticholic group had increase serum cholesterol and LDL cholesterol. This study looked at a subgroup of patients in the FLINT study who had undergone liver biopsies.

E Vilar-Gomez et al. Gastroenterol 2015; 149: 367-78. This prospective study of 293 patients with histologically-proven NASH were followed after undergoing lifestyle changes for 52 weeks. At week 52, 88 subjects (30%) had lost ≥5% of their weight.  Degree of weight loss was independently associated with improvements in all NASH-related histologic parameters (steatohepatitis, NAS activity score, and fibrosis.

G Lassailly et al. Gastroenterol 2015; 149: 379-88. Between 1994-2013, 109 morbidly-obese patients with histologically-proven NASH underwent bariatric surgery.  One year after surgery, NASH had disappeared from 85% of the patients.

P Angulo et al. Gastroenterol 2015; 149: 389-97. In this retrospective analysis of 619 patients with NAFLD (1979-2005), the authors noted that “fibrosis stage, but no other histologic features of steatohepatitis, were associated independently with long-term overall mortality, liver transplantation, and liver-related events.”