Rare Daily Staff

Albireo reported positive final results from a mid-stage trial of its experimental therapy for progressive familial intrahepatic cholestasis, a rare liver disease. 

One of the trial investigator will present the results of the mid-stage study at the American Association for the Study of Liver Diseases’ The Liver Meeting 2017 in Washington, D.C. in a poster presentation October 22.

The open label, multicenter, dose-finding mid-stage clinical trial assessed the safety and tolerability of A4250 and explored changes in serum bile acid levels, pruritus, and sleep disturbance. The open label study was not powered for formal statistical analyses. 

A4250 is a highly potent and selective inhibitor of the ileal bile acid transporter. It has minimal systemic exposure and acts locally in the gut. A total of 20 patients aged 1 to 17 years old with a pediatric cholestatic liver disease, including PFIC (subtype 1, 2 or 3), Alagille syndrome, biliary atresia or intrahepatic cholestasis, were enrolled in the study. Four of the patients reenrolled into a second dose group. A4250 was administered orally once daily for four weeks at five different doses.

In the study, A4250 reduced serum bile acids and improved pruritus in most patients, particularly patients with PFIC. The company said A4250 exhibited a favorable overall tolerability profile in the study, with all patients completing the four-week treatment period and no reports of diarrhea associated with multiple dose therapy.

“The findings from this Phase 2 study of A4250 on various efficacy measures, and the safety and tolerability profile shown, are promising,” said Ekkehard Sturm, head of pediatric gastroenterology-hepatology, liver and intestinal transplantation at Children’s Hospital, University of Tuebingen in Germany. “The compelling data in PFIC patients in particular illustrate that A4250 has potential to become a welcomed treatment alternative to the current standards of care, which are bile diversion surgery or transplantation. Further study of A4250 in PFIC is warranted.”

A4250 demonstrated a mean reduction in serum bile acid levels in all five dose groups in the study, with substantial reductions (ranging from 43 to 98 percent) in 80 percent of the PFIC patients. In addition, the majority of patients showed improvement in pruritus on three different assessment scales, with a significant correlation between reduction in serum bile acid and improvement in pruritus, as well as improvement in sleep disturbance.

There were no serious adverse events reported in the study that were considered to be drug related. Most adverse events, including some increased transaminases, were mild, transient and assessed as either unrelated to study drug or the relationship was unclear. 

The U.S. Food and Drug Administration and European Medicines Agency granted A4250 orphan drug designation for PFIC. The EMA also granted A4250 access to the Priority Medicines program for the treatment of PFIC.

October 20, 2017

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