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Albireo Reports Positive Topline Data from Phase 3 Trial of Bylvay in Alagille Syndrome

October 11, 2022

Albireo Pharma, a rare disease company developing novel bile acid modulators to treat pediatric and adult liver diseases, reported positive topline results from the phase 3 ASSERT study evaluating the safety and efficacy of Bylvay in Alagille syndrome patients from birth to early adulthood.

Photo: Ron Cooper, president and CEO of Albireo

Alagille syndrome, or ALGS, is a rare, multisystem genetic disorder that Albireo estimates impacts 25,000 people globally. ALGS can affect the liver, heart, skeleton, eyes, central nervous system, kidneys and facial features. Liver damage is caused by a paucity of bile ducts preventing bile flow from the liver to the small intestine. Approximately 95 percent of patients with the condition present with chronic cholestasis, usually within the first three months of life, and as many as 88 percent also present with severe, intractable pruritus.

The global, double-blind, randomized, placebo-controlled trial met its primary endpoint of improvement in pruritus and its key secondary endpoint of reduction in serum bile acids. There were no patient discontinuations and Bylvay was well-tolerated, with low rates of drug-related diarrhea. Albireo has engaged in discussions with U.S. and EU regulatory authorities about the phase 3 study design, and both have indicated that a successful single study would be sufficient for approval. The company plans to immediately submit regulatory filings in the U.S. and E.U.

“Our ASSERT phase 3 study demonstrated early, rapid, and sustained effects on reducing pruritus and bile acids in Alagille syndrome, as it did in the phase 3 PFIC study,” said Ron Cooper, president and CEO of Albireo. “We have successfully completed two of three gold standard pediatric liver disease studies, look forward to imminent full enrollment of a third phase 3 with our BOLD biliary atresia study.”

The company said it has more than $270 million in cash, sufficient runway to execute on its plans.

A potent, once-daily, non-systemic ileal bile acid transport inhibitor, Bylvay has minimal systemic exposure and acts locally in the small intestine. Bylvay is already approved in the U.S. for the treatment of pruritus in patients 3 months of age and older in all types of progressive familial intrahepatic cholestasis (PFIC), and in Europe for the treatment of all types of PFIC in patients aged 6 months or older.

“The robust results from the ASSERT phase 3 trial are important because physicians urgently need more options in the treatment of Alagille syndrome. Bylvay reduced the devastating pruritus, which is so common among this patient population and critical to helping us improve sleep, among other burdens of the disease,” said Nadia Ovchinsky, pediatric gastroenterologist and hepatologist, Children’s Hospital at Montefiore and ASSERT principal investigator. “The study also showed Bylvay reduced serum bile acid levels, which could indicate that Bylvay may diminish the severity of liver disease over time, an important consideration for me as a treating physician.”

ASSERT is a prospective intervention trial with 32 sites across North America, Europe, Middle East, and Asia Pacific. The double-blind, randomized, placebo-controlled trial was designed to evaluate the safety and efficacy of 120 µg /kg/day Bylvay (odevixibat) for 24 weeks in relieving pruritus in patients with ALGS. Key secondary endpoints measure serum bile acid levels and safety and tolerability. The trial enrolled patients aged 0 to 17 years of age with a genetically confirmed diagnosis of ALGS. The primary efficacy endpoint was a change from baseline to month 6 in pruritus measured by scratching with the PRUCISION Observer-Reported Outcome scratching score caregiver instrument (0-4 point scale). The key secondary efficacy endpoint was a change in serum bile acid responses from baseline to the average of weeks 20 and 24.

In the primary analysis, the study met the primary endpoint showing statistically significant reduction in pruritus from baseline at month 6, compared to the placebo arm (p=0.002). The study also met the key secondary endpoint showing a statistically significant reduction in serum bile acid concentration from baseline to the average of weeks 20 and 24, compared to the placebo arm (p=0.001). Statistically significant improvements in multiple sleep parameters were observed as early as week 1-4 compared to patients on placebo with continued improvement through week 24. In the study, there were no patient discontinuations. Bylvay was well tolerated, with an overall adverse event incidence similar to placebo and a low incidence of drug-related diarrhea. Full results from the phase 3 clinical trial will be presented at a future scientific meeting.

Albireo continues to enroll patients in the phase 3 BOLD study, which is the first and only pivotal trial of an ileal bile acid transport inhibitor in biliary atresia (BA) and remains on track to fully enroll by end of year, with topline data planned for 2024. BA is the most common pediatric cholestatic liver disease with no approved drug treatment. With clinical programs in ALGS and BA, Bylvay has the potential to be approved for three pediatric cholestatic liver diseases.

Author: Rare Daily Staff

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