Press Release Details

• First successful global gold standard pediatric Phase 3 trial ever conducted in cholestatic liver disease
• PEDFIC 1 & 2 studies were foundational for the approval of Bylvay in the U.S. and Europe 
• Study shows Bylvay provided statistically significant improvements in pruritus severity scores and reductions in serum bile acid levels
  

BOSTON, July 06, 2022 (GLOBE NEWSWIRE) -- Albireo Pharma, Inc. (Nasdaq: ALBO), a rare liver disease company developing novel bile acid modulators, today announced that The Lancet Gastroenterology & Hepatology published the results of the pivotal PEDFIC 1 trial, which evaluated Bylvay^® (odevixibat) for the treatment of progressive familial intrahepatic cholestasis (PFIC). The study met both of its two primary endpoints, demonstrating that Bylvay provided statistically significant improvements in pruritus severity scores and reductions in serum bile acid levels, with rapid, sustained, and consistent results. The full manuscript of the PEDFIC 1 study is available on The Lancet Gastroenterology & Hepatology website.

A potent, once-daily, non-systemic ileal bile acid transporter inhibitor (IBATi), Bylvay has minimal systemic exposure and acts locally in the small intestine. Bylvay was recently approved in the U.S. for the treatment of pruritus in patients 3 months of age and older with all types of PFIC, and in Europe for the treatment of all types of PFIC in patients aged 6 months or older, based on the PEDFIC 1 study and PEDFIC 2 open-label extension (OLE) study.

“The PEDFIC 1 study is the largest trial ever completed in PFIC and we are pleased that a prestigious journal has recognized the quality of the science and importance of the landmark results,” said Ron Cooper, President and Chief Executive Officer of Albireo. “The study outcomes have been positively received by physicians and payors enabling swift pricing and reimbursement reviews of Bylvay, helping to accelerate access to this much needed medicine for patients suffering with this cholestatic liver disease.”

The publication includes data from the randomized, double-blind, placebo-controlled Phase 3 PEDFIC 1 global study. Within the study findings:

• The study was conducted from May 2018 to July 2020 and evaluated 62 patients, aged 6 months to 15.9 years, with PFIC type 1 or type 2. Patients were randomized to receive either a 40 µg/kg/day (n=23) or 120 µg/kg/day (n=19) oral dose of Bylvay (odevixibat) or placebo (n=20) once daily for 24 weeks.
• The model-adjusted (least squares) mean proportion of positive pruritus assessments (PPAs) at the patient level was significantly higher with Bylvay, at 55% for the all-Bylvay group (58% and 52% in the Bylvay 40 and 120 μg/kg/day groups, respectively) compared to 30% in the placebo group (p=0.0038).
• The proportion of patients achieving a serum bile acid response, defined as a ≥70% reduction from baseline in fasting serum bile acids or serum bile acids ≤70 μmol/L at week 24, was 33% in the all-Bylvay group (including 43% and 21% of patients in the Bylvay 40 and 120 μg/kg/day groups, respectively), compared to no patients in the placebo group (p=0.0030).
• The study also showed meaningful improvements in secondary endpoints related to pruritus and serum bile acids, with a greater proportion of patients treated with Bylvay having a clinically meaningful improvement in pruritus at week 24, defined as a drop from baseline of 1.0 point or more on the 0−4 point scale, than patients treated with placebo (43% vs 11%, respectively). Improvement in pruritus among Bylvay-treated patients was observed by week 4 of treatment.
• Consistent with improvements observed with pruritus, treatment with Bylvay improved patients’ sleep by weeks 21−24 as reported by caregivers, with reductions from baseline in the percentage of days needing help falling asleep, −43% for the all-Bylvay group versus −3% for the placebo group; soothing, −44% versus −8%, respectively; and sleeping with the caregiver, −42% versus −5%, respectively.
• Mean serum bile acid levels decreased by 114.3 μmol/L in the all-Bylvay group at weeks 22 through 24, compared to an increase of 13.1 μmol/L in the placebo group (p=0.0022). Changes from baseline in serum bile acids were also observed as early as week 4 of Bylvay treatment.
• In the study, Bylvay was well tolerated, with an overall adverse event incidence similar to placebo. There were no drug-related serious adverse events reported during the study. Drug-related treatment-emergent adverse events of diarrhea/frequent bowel movements occurred in 10% (4/42) of Bylvay-treated patients and in 5% (1/20) of placebo-treated patients. In same study, 31% (13/42) of patients on Bylvay reported diarrhea compared with 10% (2/20) of placebo.
  

Patients with PFIC have impaired bile flow, or cholestasis, and the resulting bile build-up in liver cells causes liver disease and symptoms including intense itching, poor sleep, delayed growth and diminished quality of life. The harmful impacts of the disease extend to parents and caregivers, as the 2022 multinational PICTURE study revealed that PFIC negatively affects caregivers’ quality of life, relationships, and career prospects.

The results from the PEDFIC studies provide confidence in the translatability of the data in Alagille syndrome (ALGS) and biliary atresia and the two Phase 3 studies in progress. The ASSERT study in ALGS is fully enrolled and topline data is expected by the end of the year. The BOLD study in biliary atresia is expected to complete enrollment this year with topline data available in 2024.

About Bylvay (odevixibat)

Bylvay is the first drug 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). Limitation of Use: Bylvay may not be effective in PFIC type 2 patients with ABCB11 variants resulting in non-functional or complete absence of bile salt export pump protein (BSEP-3). The European Commission (EC) and UK Medicines and Healthcare Products Regulatory Agency (MHRA) have also granted marketing authorization of Bylvay for the treatment of PFIC in patients aged 6 months or older. Bylvay is available in Germany and the UK and will be available for sale in other European countries following pricing and reimbursement approval. A potent, once-daily, non-systemic ileal bile acid transporter inhibitor (IBATi), Bylvay has minimal systemic exposure and acts locally in the small intestine. Bylvay can be taken as a capsule for patients that are able to swallow capsules, or opened and sprinkled onto food, which is a factor of key importance for adherence in a pediatric patient population. The most common adverse reactions for Bylvay are diarrhea, liver test abnormalities, vomiting, abdominal pain, and fat-soluble vitamin deficiency. The medicine can only be obtained with a prescription. For more information about using Bylvay, see the package leaflet or contact your doctor or pharmacist. For full prescribing information, visit www.bylvay.com.

In the U.S. and Europe, Bylvay has orphan exclusivity for its approved PFIC indications, and orphan designations for the treatment of ALGS, biliary atresia and primary biliary cholangitis. Bylvay is being evaluated in the ongoing PEDFIC 2 open-label trial in patients with PFIC, in the BOLD Phase 3 study for patients with biliary atresia and the ASSERT Phase 3 study for ALGS.

Important Safety Information

• The most common adverse reactions for Bylvay are diarrhea, liver test abnormalities, vomiting, abdominal pain, and fat-soluble vitamin deficiency.
• Liver Test Abnormalities: Patients should obtain baseline liver tests and monitor during treatment. Dose reduction or treatment interruption may be required if abnormalities occur. For persistent or recurrent liver test abnormalities, consider treatment discontinuation.
• Diarrhea: Treat dehydration. Treatment interruption or discontinuation may be required for persistent diarrhea.
• Fat-Soluble Vitamin (FSV) Deficiency: Patient should obtain baseline vitamin levels and monitor during treatment. Supplement if deficiency is observed. If FSV deficiency persists or worsens despite FSV supplementation, discontinue treatment.

About Albireo

Albireo Pharma is a rare disease company focused on the development of novel bile acid modulators to treat rare pediatric and adult liver diseases. Albireo’s lead product, Bylvay, was approved by the U.S. FDA as the first drug for the treatment of pruritus in all types of progressive familial intrahepatic cholestasis (PFIC), and it is also being developed to treat other rare pediatric cholestatic liver diseases with Phase 3 trials in Alagille syndrome (ALGS) and biliary atresia, as well as Open-label Extension (OLE) studies for PFIC and ALGS. In Europe, Bylvay has been approved for the treatment of PFIC with pricing listing in Germany and guidance from the National Institute for Health and Care Excellence (NICE) recommending Bylvay for use in the National Health Service in England, Wales and Northern Ireland. The Company has also completed a Phase 1 clinical trial for A3907 to advance development in adult cholestatic liver disease, with IND-enabling studies progressing with A2342 for viral and cholestatic liver disease. Albireo was spun out from AstraZeneca in 2008 and is headquartered in Boston, Massachusetts, with its key operating subsidiary in Gothenburg, Sweden. For more information on Albireo, please visit www.albireopharma.com.

Forward-Looking Statements

This press release includes “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include statements, other than statements of historical fact, regarding, among other things: Albireo’s commercialization plans; the plans for, or progress, scope, cost, initiation, duration, enrollment, results or timing for availability of results of, development of Bylvay or any other Albireo product candidate or program; the PEDFIC 2 open-label trial in patients with PFIC; the pivotal trial for Bylvay in biliary atresia (BOLD); the pivotal trial for Bylvay in Alagille syndrome (ASSERT);; the target indication(s) for development or approval; the timing for initiation or completion of or availability or reporting of results from any clinical trial, including the long-term open-label extension study for Bylvay in PFIC, the BOLD and ASSERT trials, potential regulatory approval and plans for potential commercialization of Bylvay in additional countries; the potential benefits or competitive position of Bylvay or any other Albireo product candidate or program or the commercial opportunity in any target indication; or Albireo’s plans, expectations or future operations, financial position, revenues, costs or expenses. Albireo often uses words such as “anticipates,” “believes,” “plans,” “expects,” “projects,” “future,” “intends,” “may,” “will,” “should,” “could,” “estimates,” “predicts,” “potential,” “planned,” “continue,” “guidance,” or the negative of these terms or other similar expressions to identify forward-looking statements. Actual results, performance or experience may differ materially from those expressed or implied by any forward-looking statement as a result of various risks, uncertainties and other factors, including, but not limited to: results achieved in Bylvay in the treatment of patients with PFIC may be different than observed in clinical trials, and may vary among patients; potential negative impacts of the COVID-19 pandemic, including on manufacturing, supply, conduct or initiation of clinical trials, or other aspects of our business; whether favorable findings from clinical trials of Bylvay to date, including findings in indications other than PFIC, will be predictive of results from other clinical trials of Bylvay; the timing for initiation or completion of, or for availability of data from, clinical trials of Bylvay, including BOLD and ASSERT and the outcomes of such trials; Albireo’s ability to obtain coverage, pricing or reimbursement for approved products in the United States or Europe; delays or other challenges in the recruitment of patients for, or the conduct of, the Company’s clinical trials; and the Company’s critical accounting policies. These and other risks and uncertainties that Albireo faces are described in greater detail under the heading “Risk Factors” in Albireo’s most recent Annual Report on Form 10-K or in subsequent filings that it makes with the Securities and Exchange Commission. As a result of risks and uncertainties that Albireo faces, the results or events indicated by any forward-looking statement may not occur. Albireo cautions you not to place undue reliance on any forward-looking statement. In addition, any forward-looking statement in this press release represents Albireo’s views only as of the date of this press release and should not be relied upon as representing its views as of any subsequent date. Albireo disclaims any obligation to update any forward-looking statement except as required by applicable law.

Media Contact:
Colleen Alabiso, 857-356-3905, colleen.alabiso@albireopharma.com
Lance Buckley, 917-439-2241, lbuckley@lippetaylor.com

Investor Contact:
Hans Vitzthum, LifeSci Advisors, LLC., 617-430-7578

Source: Albireo Pharma, Inc.