US regulators have issued a safety communication warning of the risk for serious liver injury and death from incorrect dosing of Intercept Pharmaceuticals' Ocaliva in patients with primary biliary cholangitis.

The US Food and Drug Administration said that in the 13 months since Ocaliva (obeticholic acid) was cleared for use in May 2016 for the chronic liver disease, 19 cases of death had been identified, of which eight provided information about the 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. Crucially, in seven of these eight cases patients with moderate to severe decreased liver function were receiving Ocaliva 5mg daily, instead of a dose no greater than 10mg twice weekly as recommended by the regulator.

The agency also 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 the incorrect dose of Ocaliva 5mg daily. Three of these six patients died, which were included in the 19 death cases cited by the regulator.

The FDA is advising healthcare professionals to determine the patient’s baseline liver function prior to starting treatment with the drug, and reiterated that those with moderate to severe liver impairment should be started on the approved dosing schedule of 5mg once weekly, rather than the 5mg daily dosing used for other PBC patients.

Also, disease progression should be monitored and dosing adjusted where necessary, and if liver injury is expected, treatment with the drug should be discontinued.

The FDA’s warning over the “high number of deaths and worsening of PBC cases strikes us as particularly concerning,” said Leerink analyst Joseph Schwartz, according to media reports, “and could tilt the FDA more toward a black box warning”.

However, Reuters reports that analysts at RBC Capital Markets were less concerned over the news, noting that the risks are already included on the drug’s label, and that the affected patients account for less that five percent of the overall PBC population.

Intercept’s shares dropped more than 10 percent following the news.

Ocaliva, a highly selective agonist of a nuclear receptor expressed in the liver and intestine that regulates bile acid, inflammatory, fibrotic and metabolic pathways, is available on the NHS to treat patients with the PBC condition who do not fully respond to, or are intolerant to, current treatment and remain at risk of their disease progressing toward cirrhosis, liver transplantation or death.