BOSTON—Albireo Pharma, Inc. has reported advances and new initiatives in the company’s clinical program for odevixibat. Odevixibat is an oral, once-daily capsule in development for the treatment of progressive familial intrahepatic cholestasis (PFIC), biliary atresia and Alagille syndrome.
“Odevixibat is a potent and selective inhibitor of the ileal bile acid transporter (IBAT), sometimes also referred to as the apical sodium dependent bile acid transporter (ASBT), that has minimal systemic exposure at therapeutic doses and acts locally in the gut,” says Albireo’s website. “In an open label Phase 2 study in children with cholestatic liver disease and pruritus, odevixibat showed reductions in serum bile acids and pruritus in most patients and exhibited a favorable overall tolerability profile.”
“When the flow of bile from the liver stops or is disrupted, known as cholestasis, bile acids accumulate in the liver. Elevated bile acid levels in the liver and serum are primary characteristics of cholestatic liver diseases and have been linked to severe pruritus in these patients. 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,” the website continues. “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.”
The U.S. Food and Drug Administration (FDA) has cleared Albireo’s investigational new drug (IND) application to initiate a global pivotal trial in biliary atresia. Following scheduled FDA interactions in the first quarter of 2020, the company plans to commence an additional pivotal program in Alagille syndrome by the end of 2020. Albireo also expects topline data from its Phase 3 trial in PFIC in mid-2020.
“We continue to believe in the potential for odevixibat to address unmet needs across multiple rare cholestatic liver diseases, and we remain steadfastly committed to patients and their families living with these devastating conditions. We expect our Phase 3 trial in PFIC will be fully randomized in the coming days, and we expect to report topline data in mid-2020,” stated Ron Cooper, Albireo’s president and chief executive officer. “I am particularly excited to announce that the FDA has cleared our IND, and we expect to initiate a precedent-setting pivotal trial in biliary atresia in the first half of 2020.”
The PEDFIC 1 trial is studying high and low dose odevixibat in both PFIC type 1 and type 2 patients aged 6 months to 18 years. Patients randomized to odevixibat are being treated with high (120µg/kg) or low (40µg/kg) dose once-daily oral capsules or sprinkles. The trial uses Albireo’s planned commercial formulation of odevixibat, which does not require refrigeration.
PEDFIC 1 has a target of 60 patients. 59 have been randomized, and the randomization visit for the final patient has been scheduled in the coming days. Albireo expects top-line data from PEDFIC 1 in mid-2020, with potential first regulatory approval and odevixibat launch in the second half of 2021.
Biliary atresia is a rare disease that impacts an estimated 15,000-20,000 people in the U.S. and the EU. It’s the leading cause of liver transplants among children. Albireo’s planned double-blind, placebo controlled pivotal trial in biliary atresia is designed to enroll approximately 200 patients at 70 sites globally. Patients will receive either placebo or high-dose (120µg/kg) odevixibat once daily. The primary endpoint is survival with native liver after 2 years of treatment. The FDA and the European Commission have granted orphan designations for odevixibat to treat biliary atresia.
Albireo has been evaluating a proposed pivotal study design for odevixibat in Alagille syndrome as well, and the company plans to initiate the trial later this year. The FDA and the European Commission have also granted orphan designations to odevixibat for the treatment of Alagille syndrome.
Albireo also announced today a proposed underwritten public offering of the company’s common stock. In connection with the offering, Albireo intends to grant the underwriters a 30-day option to purchase up to an additional 15% of the number of shares of common stock sold in the offering. All of the offering shares will be sold by Albireo. The offering is subject to market and other conditions.
Jefferies Group LLC is acting as the sole book-running manager and representative of the underwriters for the offering. A preliminary prospectus describing the terms of the offering and a prospectus supplement will be filed with the U.S. Securities and Exchange Commission (SEC), and made available on the SEC’s website.