Albireo Completes Phase 3 BOLD Study Enrollment of Bylvay(R) in Biliary Atresia

– BOLD is the first, largest, and only global Phase 3 trial designed to meet regulatory agencies' requirements

– On track to report topline data by the end of 2024, reinforcing Bylvay's expected position as first IBAT inhibitor tomarket in biliary atresia

BOSTON, Nov. 02, 2022 (GLOBE NEWSWIRE) -- Albireo Pharma, Inc. (Nasdaq: ALBO), a rare disease company developing novel bile acid modulators to treat pediatric and adult liver diseases, today announced the completion of patient enrollment in the BOLD (Biliary atresia and the use of Odevixibat in treating Liver Disease) study, a global gold standard Phase 3 pivotal trial of Bylvay (odevixibat) in 205 patients with biliary atresia (BA) over 24 months. Topline results are expected to be available by the end of 2024, consistent with previous guidance. Recent discussions with health authorities confirm that an outcome study would be necessary to achieve approval or to fulfill the requirements of an accelerated filing. Albireo has engaged in discussions with the FDA and EMA about the BOLD Phase 3 study design; both have recently indicated that a positive single study could be sufficient for approval.

“Enrolling 205 children suffering from biliary atresia into the largest Phase 3 pediatric cholestasis trial ever is a significant achievement allowing us to evaluate Bylvay in an unprecedented number of patients across geographies,” said Jan Mattsson, Chief Scientific Officer and Head of R&D at Albireo. “Biliary atresia is the most common pediatric cholestatic liver disease and given our recent successes with Bylvay Phase 3 studies in PFIC and Alagille syndrome, we feel confident of a positive outcome and look forward to being able to provide these children the first approved drug treatment for biliary atresia.”

The BOLD study is the first and only global Phase 3 study of an ileal bile acid transporter (IBAT) inhibitor in biliary atresia with 58 clinical trial sites in 19 countries. BOLD is a double-blind, randomized, placebo-controlled trial that measures native liver survival with Bylvay over 24 months in children with biliary atresia. Bylvay has received orphan drug designation for biliary atresia in the United States and European Union.

“The completion of enrollment for the BOLD trial is a major milestone for the children with biliary atresia and their families. I and my pediatric hepatology colleagues from around the world await completion of the trial in order to evaluate the results. As such, we expect it to provide important insights into the mechanisms of disease progression and potentially demonstrate that we can change the outcome of this disease with a drug for the first time,” said Saul J. Karpen, M.D., Ph.D., pediatric hepatologist at Children’s Healthcare of Atlanta/Emory University School of Medicine and lead investigator of the BOLD trial. “With approximately 75% of biliary atresia patients needing a liver transplant during childhood, the medical community is eager to have a targeted therapeutic that directly addresses the intrahepatic accumulation of bile acids. If this intervention improves the response to Kasai portoenterostomy, it could ultimately delay or prevent liver transplant for babies with this serious and perplexing disease, one that is currently without any effective medical therapies.”

Biliary atresia is a rare pediatric liver disease and yet the most common pediatric cholestatic liver disease and the leading cause of pediatric liver transplant across all diseases with symptoms typically developing about two to eight weeks after birth. Damaged or absent bile ducts result in bile and bile acids being trapped inside the liver, quickly resulting in cirrhosis and even liver failure. The disease impacts an estimated 45,000 people around the globe and is the leading cause of liver transplants among children. There are no approved pharmacological treatments for biliary atresia.

“It is terrifying to receive a diagnosis of biliary atresia for your newborn, and even worse, when you are informed that your child will likely need a liver transplant. We are very excited that the BOLD trial is fully enrolled, and we eagerly await the results, hoping that families will finally have an option that could help avoid a liver transplant,” said Jennifer Lau, Co-Founder and President, BARE Inc.

Bylvay is a potent, oral, once-daily, non-systemic ileal bile acid transport inhibitor (IBATi), with minimal systemic absorption that 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 PFIC, and in Europe for the treatment of all types of PFIC in patients aged 6 months or older. In addition, Bylvay met primary endpoint of improvement in pruritus and key secondary endpoint of reduction in serum bile acids in a recently announced Phase 3 ASSERT trial in patients with Alagille syndrome.

About BOLD

BOLD ( NCT04336722 ) is a double-blind, randomized, placebo-controlled trial to evaluate the efficacy and safety of odevixibat in children who have biliary atresia and have undergone a Kasai procedure before the age of three months. Children in the treatment arm receive odevixibat (120 μg/kg) orally once daily for 24 months. The primary efficacy endpoint is improvement in the proportion of patients who are alive and have not undergone a liver transplant after two years of treatment compared to placebo, and secondary outcome measures include time to onset of any sentinel events, total bilirubin levels and serum bile acid levels. The trial enrolled 205 patients at 58 sites globally.

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. A potent, once-daily, non-systemic ileal bile acid transport inhibitor, 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 open-label trial 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 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 a completed Phase 3 trial in Alagille syndrome (ALGS), an ongoing Phase 3 study in biliary atresia, as well as Open-label Extension (OLE) studies for PFIC and ALGS. In Europe, Bylvay is reimbursed for the treatment of PFIC in Germany, England, Wales & Northern Ireland, Scotland, Italy, and Belgium. 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 expected cash runway; 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, A3907, A2342 or any other Albireo product candidate or program; the target indication(s) for development or approval; the timing for anticipated regulatory filings; discussions with the FDA or EMA regarding our programs; potential regulatory approval and plans for potential commercialization of Bylvay in biliary atresia or ALGS or Albireo’s other product candidates; 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 whether we will achieve a positive outcome in the BOLD trial on the timeline we expect, and if so, whether results from the BOLD study will be sufficient for approval by the FDA and EMA, or whether the FDA and EMA will require additional information, whether we will be able to provide in a timely manner any additional information that the FDA and EMA request, and whether such additional information will be satisfactory to the FDA and EMA; there are no guarantees that Bylvay will be commercially successful; we may encounter issues, delays or other challenges in commercializing Bylvay; whether Bylvay receives adequate reimbursement from third-party payors; the degree to which Bylvay receives acceptance from patients and physicians for its approved indication; challenges associated with execution of our sales activities, which in each case could limit the potential of our product; challenges associated with supply and distribution activities, which in each case could limit our sales and the availability of our product; results achieved in Bylvay in the treatment of patients with PFIC or other approved indications 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 PFIC, ALGS and other indications, will be predictive of results from other clinical trials of Bylvay; there is no guarantee that Bylvay will be approved in jurisdictions or for indications (such as biliary atresia or ALGS) beyond the jurisdictions in which or indications for which Bylvay is currently approved; there is no guarantee that our other product candidates will be approved; estimates of the addressable patient population for target indications may prove to be incorrect; the outcome and interpretation by regulatory authorities of the ongoing third-party study pooling and analyzing of long-term PFIC patient data; the timing for initiation or completion of, or for availability of data from, clinical trials of Bylvay, including BOLD, and the Phase 2 clinical trial of A3907, 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; any repurchase by the Company of Sagard’s interest in the royalty interest payments under our royalty monetization agreement with Sagard could materially impact our financial condition; 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 Contacts:
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