FDA Issues Warning After Deaths Associate with Improper Dosing of Intercept’s Ocaliva

Rare Daily Staff

The U.S. Food and Drug Administration issued a warning that incorrect dosing of Ocaliva, Intercept Pharmaceuticals’ treatment for a rare, chronic liver disease known as primary biliary cholangitis, has been linked to several cases of death and serious liver injury.

Primary biliary cholangitis, or PBC, causes the bile ducts in the liver to become inflamed, damaged and destroyed. This causes bile, a fluid that helps in digestion, to build up in the liver. This build-up damages the liver over time, eventually causing it to lose its ability to function.

The FDA said it identified 19 patient deaths. Of these, eight provided information about the patient’s cause of death. In seven of those cases reported the cause of death as worsening PBC disease, with cardiovascular disease cited in the other case. Seven of these eight cases described patient with moderate to severe decreased liver function who received 5 mg daily of Ocaliva, instead of a dose no greater than 10 mg twice weekly as recommended in the FDA drug label.

The agency also said it identified 11 cases of serious liver injury with Ocaliva use. Six of the patients who had moderate or severe decreases in liver function at baseline and developed serious liver injury were receiving Ocaliva 5 mg daily, instead of a dose no greater than 10 mg twice weekly as recommended by FDA in the drug label. Three of these six patients died and were included in the 19 death cases the FDA reported.

The FDA approved Ocaliva in May 2016. The agency’s adverse event reporting system only includes reports submitted to the FDA. The agency said there may be other cases it was not aware of at this time.

Intercept said it has begun working with the FDA on updates to the label to better ensure appropriate and safe use of Ocaliva.

In a letter to healthcare professionals, Intercept noted that the deaths that have been reported have been associated with a dosing of the drug that was seven times greater than the recommended weekly dose. It reinforced the importance of recommended label dosing and the need to monitor patients with regard to progression of their disease.

The safety concerns could prove pose a new hurdle to Intercept, which is working to expand the use of Ocaliva to include NASH, a big and potentially lucrative market for the drug.

September 22, 2017