BOSTON—Rare pediatric liver diseases can be debilitating; cholestasis is any condition in which the flow of bile from the liver is slowed or blocked. Albireo Pharma Inc., a clinical-stage orphan pediatric liver disease company developing novel bile acid modulators, is looking for answers to both.
Albireo announced results in Alagille syndrome and biliary atresia patients from its completed Phase 2 clinical trial evaluating A4250—now known as odevixibat—in pediatric cholestasis. These results were presented at the European Association for the Study of the Liver (EASL) meeting recently in Vienna.
The company, which was spun out of AstraZeneca, believes bile acid modulation has “the potential to create transformative drugs to treat rare diseases involving lipids, glucose and energy homeostasis,” according to Ron Cooper, president and CEO of Albireo. “These data, and our key regulatory designations in biliary atresia, Alagille and PFIC (progressive familial intrahepatic choleostasis) in the U.S. and the EU, reinforce the potential of odevixibat to achieve that goal. To people suffering with these diseases, Albireo represents hope.”
Data from the clinical trial demonstrated that the drug reduced serum bile acids (sBA) and improved pruritus (chronic itching) in the majority of biliary atresia and Alagille patients, indicating the drug candidate’s potential to be the first pharmacologic treatment for numerous cholestatic liver diseases. There is no approved pharmacologic treatment for Alagille and biliary atresia.
In the trial, odevixibat demonstrated reductions in sBAs of 57.6 percent and 50.8 percent in two biliary atresia patients with high baseline bile acids (> 130 μmol/L). This marks the first time any company has generated positive data suggesting an effect on bile acids and pruritus in biliary atresia using a drug therapy. These data form the basis for a pivotal development program which Albireo plans to initiate this year.
Odevixibat was generally well tolerated in patients with Alagille and biliary atresia. There were mild and transient adverse events, including some increased transaminases. Two Alagille patients with high baseline transaminase levels experienced further increases, which led the researchers to refrain from escalating the dosage.
Lead investigator Dr. Ulrich Baumann, a professor of pediatric gastroenterology and hepatology at Hannover Medical School in Hannover, Germany, who presented the Alagille results, said, “Liver damage caused by cholestasis is a hallmark of Alagille syndrome, a rare and life-threatening liver disease, and there is an urgent need for a non-invasive pharmacologic treatment option. The Alagille patient data from this Phase 2 trial, including the meaningful reductions in serum bile acids and improved pruritus and sleep scores, indicate that A4250 could be a promising therapy for cholestatic liver diseases like Alagille, and suggest that further investigation of A4250 in children with Alagille is warranted.”
Investigator Dr. Ekkehard Sturm, head of pediatric gastroenterology-hepatology, liver and intestinal transplantation at Children's Hospital of the University of Tübingen in Germany, who presented the biliary atresia results, noted, “Although biliary atresia is an orphan disease, it is the most common pediatric liver disease for which transplants are done, and there are no approved pharmacological treatments. The A4250 data, though limited, are consistent with results from the overall study population of pediatric patients with chronic CLD and are encouraging. I am pleased to see that Albireo plans to embark on a biliary atresia pivotal program, as the unmet need for these patients is significant.”
Odevixibat is a highly potent and selective inhibitor of the ileal bile acid transporter (IBAT). This IBAT inhibitor approach works to drain the liver of excess bile acids, Cooper explained. Odevixibat is currently being evaluated in a Phase 3 program for the treatment of its lead indication, cholestatic liver disease progressive familial intrahepatic cholestasis (PFIC). The drug candidate is being evaluated at more than 40 clinical sites, and data are expected end of 2019 or early 2020, Cooper said. He anticipates approval and launch of odevixibat in the first half of 2021.
According to Albireo’s website, “The IBAT is primarily responsible for mediating the uptake of bile acids from the small intestine to the liver as part of a process known as enterohepatic circulation. Typically, approximately 95 percent of bile acids are recirculated via the IBAT to the liver. Accordingly, a product capable of inhibiting the IBAT could lead to a reduction in bile acids returning to the liver and may represent a promising approach for treating cholestatic liver diseases.”
Cooper summarized, “Albireo is excited to have the drug in Phase 3 trials and to expand into other diseases. It’s an exciting time for the company and for the patients we serve."