Alagille Syndrome
Progressive Familial Intrahepatic Cholestasis

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

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lbireo Pharma, Inc, a rare disease company developing novel bile acid modulators to treat pediatric and adult liver diseases, today announced positive topline results from the Phase 3 ASSERT study evaluating the safety and efficacy of Bylvay in Alagille syndrome (ALGS) patients from birth to early adulthood. The global, double-blind, randomized, placebo-controlled trial met its primary endpoint of improvement in pruritus (p=0.002) and its key secondary endpoint of reduction in serum bile acids (sBAs) (p=0.001). There were no patient discontinuations and Bylvay was well tolerated, with low rates of drug-related diarrhea (11.4% vs. 5.9% placebo). Albireo has engaged in discussions with the FDA and EMA about the Phase 3 study design, 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 EU.

“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 Chief Executive Officer 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, and with more than $270 million in cash, we have sufficient resources to execute on our plans. At the same time, we are seeing an acceleration in PFIC revenue and expect Q3 Bylvay sales to be above $7 million.”

A potent, once-daily, non-systemic ileal bile acid transport inhibitor (IBATi), 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,” explained Nadia Ovchinsky, MD, 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.”

Alagille syndrome, or ALGS, is a rare, multisystem genetic disorder that the Company 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% 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.

“Alagille syndrome is a devastating diagnosis and families of children with this syndrome need more treatment options,” said Roberta Smith, President, Alagille Syndrome Alliance. “As a mother of a child living with Alagille syndrome, I know firsthand the devastation of pruritus and the terrible impact to a child’s quality of life and ability to sleep and thrive. Knowing my physician may have another treatment option is very meaningful.”

ASSERT Phase 3 Clinical Trial Data

ASSERT is a gold standard, 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 Alagille syndrome (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 (weeks 21 to 24) in pruritus measured by scratching with the PRUCISION Observer-Reported Outcome (ObsRO) scratching score caregiver instrument (0-4 point scale). The key secondary efficacy endpoint was a change in serum bile acid responses (sBAs) 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 as measured by the PRUCISION Observer-Reported Outcome scratching score (0-4 point scale), from baseline at month 6 (weeks 21 to 24), 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 (11.4% vs. 5.9% placebo). Full results from the Phase 3 clinical trial will be presented at a future scientific meeting.


Source: Albireo Pharma, Inc.