Albireo Pharma Eyes Potential Approval for First PFIC Treatment

With limited treatment options beyond invasive medical procedures, cholestatic liver diseases are devastating for adults and children. But, for these patients, there may be a bright light at the end of the tunnel in the form of Albireo Pharma’s ileal bile acid transport inhibitor (IBATi) odevixibat.

On Friday, the Boston-based company presented positive Phase III data in progressive familial intrahepatic cholestasis (PFIC) at the American Association for the Study of Liver Diseases’ annual meeting. The data confirmed treatment with odevixibat demonstrated statistically significant reductions in serum bile acids (sBAs) and improvements in pruritus in pediatric PFIC patients. Odevixibat met its primary endpoints in the PEDFIC 1 study, the first Phase III study conducted in PFIC, according to the company. Additionally, long-term data from PEDFIC 2, an open-label Phase III extension study, demonstrate continued and durable reductions in sBAs, improvements in pruritus assessments and encouraging markers of liver and growth function in patients treated up to 48 weeks with odevixibat.

Across both studies, odevixibat was generally well tolerated, and treatment-emergent adverse events were mostly mild or moderate. These studies reaffirm odevixibat’s potential to be the first drug treatment approved for patients living with PFIC.

Ron Cooper, chief executive officer of Albireo, which was spun out of AstraZeneca in 2008 following that company’s exit from the gastrointestinal space, is excited about the potential odevixibat could have for pediatric patients with PFIC, as well as other cholestatic liver diseases if other clinical studies are successful. In an interview with BioSpace, Cooper said Albireo believes odevixibat could play an important role across all these disease types by the way it helps remove excess bile through the stool.

PFIC and other cholestatic liver diseases are caused by an impaired bile flow due to genetic defects. The bile build-up in liver cells causes the liver disease. The signature symptom of PFIC and cholestatic liver disease is pruritus, an intense itching. The itch is something that can’t be scratched and Cooper said patients will severely claw at themselves as they attempt to reach the source. There are no drugs approved to treat PFIC, which can lead to cirrhosis and liver failure. Other than some off-label uses of some approved medications, such as ursodeoxycholic acid, which may show some limited efficacy, the only existing options are invasive treatments such as partial external biliary diversion and liver transplants.

“We’re really excited about what our drug can do for these patients. It hit its primary endpoint and showed high statistical significance and tolerability,” Cooper said. “These results give us confidence in the potential for IBAT inhibition in our pivotal studies in biliary atresia and Alagille syndrome.”

He noted the company has been focused on this for more than 10 years and it looks like they could break through a glass ceiling for the treatment of PFIC and potentially other pediatric cholestatic liver diseases. If studies in other diseases work out, odevixibat could become a pipeline in a product, Cooper said.

For that to happen though, odevixibat will have to be approved. The company has been working to prepare to file a New Drug Application with the U.S. Food and Drug Administration and the European Medicines Agency in the early part of 2021. Cooper said he is hopeful the company will secure priority review, which could mean potential approval and launch by the end of the year, he said.

“We’re in a very exciting stage, moving from an R&D company and becoming a commercial company,” Cooper said.

In addition to odevixibat for pediatric cholestatic liver disease, Albireo has a preclinical apical sodium-dependent bile acid transporter (ASBT) inhibitor in preclinical development. Albireo’s A3907 is a selective ASBT inhibitor being developed for adult liver diseases, including primary biliary cholangitis and primary sclerosing cholangitis. Due to oral bioavailability, A3907 can inhibit ASBT in the intestine and kidney, with the potential to increase elimination of bile acids by both fecal and urinary excretion. Preclinical data showed A3907 demonstrated an ability to increase urinary excretion of bile acids in mice and also significantly reduced plasma levels of transaminases, total cholesterol, and markers for cell damage and fibrosis, as well as liver weight and liver total cholesterol levels.

“In addition to the exciting results of our work with odevixibat in PFIC, we are progressing multiple approaches for modulating bile acids with new compounds like A3907, with the goal of finding new ways to maximize the approach to increase efficacy without sacrificing tolerability for patients,” added Cooper. “Our current work in adult liver diseases represent important pipeline developments for Albireo and reinforce our scientific leadership in bile acid modulation.”