Shire’s investigational treatment for the rare and life-threatening genetic disorder Alagille syndrome has failed to hit targets in a Phase II trial with 20 paediatric patients.

ALGS, which occurs in about one in 30,000 live births, is characterised by chronic cholestasis (accumulation of bile acids in the liver) and severe pruritus (itching), and there are no approved medical therapies for the condition.

In the trial, SHP625 failed to meet the primary or secondary target of significantly improving serum bile acid levels or pruritus, compared to placebo.

However, a post-hoc analysis showed a positive correlation between percent changes from baseline in serum bile acid levels and pruritis in the SHP625 treated group, though the number of patients in the placebo treated group was too small to make an accurate assessment of this relationship, Shire said.

On the safety side, there were no serious side effects observed in the treatment group, the most common adverse events being diarrhoea and abdominal pain, which were more frequent with SHP625 than with placebo.

Shire is studying SHP625 in several rare cholestatic liver diseases for both paediatric and adult populations. The drug blocks the reabsorption of bile in the ileum and increases faecal excretion, thereby reducing recirculation of bile acids to the liver.