Albireo Announces New Phase 3 Data for Bylvay™ (odevixibat) in PFIC and First Reveal of New Next Generation Bile Acid Modulator Data at AASLD The Liver Meeting® 2021

– Evidence of long-term clinical treatment benefit of Bylvay™ (odevixibat) showing improved liver health and function across PFIC types –

– Data show Bylvay therapy up to 128 weeks, sustained improvements in hepatic health, quality of sleep and growth, reducing disease burden –

– First data on A2342, the first oral systemic NTCP inhibitor, shows inhibition of Hepatitis B viral entry and replication in preclinical models –

– Company to host post-AASLD call on November 16, 2021 at 10 a.m. ET –

BOSTON, Nov. 12, 2021 (GLOBE NEWSWIRE) -- Albireo Pharma, Inc. (Nasdaq: ALBO), a rare liver disease company developing novel bile acid modulators, today announced new data from the Phase 3 PEDFIC 1 study and PEDFIC 2 long-term extension study of Albireo’s product, Bylvay (odevixibat), and first data from preclinical studies of cholestatic and viral disease product candidate, A2342. The data demonstrate evidence of long-term treatment benefits of Bylvay based on improved liver health and function across progressive familial intrahepatic cholestasis (PFIC) types that reduce the disease burden in the treatment of pruritus in PFIC. In addition, the company will showcase the first data from A2342 showing potential of sodium-taurocholate co-transporting peptide (NTCP) inhibition in viral and cholestatic liver diseases. The data will be presented at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting^® 2021, which is being held virtually November 12 – 15.

“The large body of evidence we have from our Phase 3 PEDFIC studies demonstrate the long-term clinical benefit of Bylvay across PFIC types, with some patients being tracked up to 128 weeks,” said Patrick Horn, M.D., Ph.D., Chief Medical Officer at Albireo. “We also see evidence of sustained improvements in hepatic health, quality of sleep and growth, which support the potential of Bylvay to reduce the disease burden and improve the standard of care.”

Bylvay PEDFIC 1 & 2 Treatment Data
The Company will present data on Bylvay in one oral presentation and four posters. Bylvay is a potent, non-systemic ileal bile acid transport inhibitor (IBATi) that is 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. PEDFIC 1 was the first and largest, global, pivotal Phase 3 study conducted in PFIC, which evaluated the efficacy and tolerability of Bylvay in reducing pruritus and serum bile acids in a randomized, double-blind, placebo-controlled trial, and PEDFIC 2 is a long-term, open-label Phase 3 extension study. Key findings include:

Data Demonstrate Long-Term Clinical Benefits of Bylvay

• Long-Term Clinical Benefit Across PFIC Types with Large and Sustained Improvements in Serum Bile Acids and Pruritus (poster #1950): Results of pooled analysis in patients with PFIC from two Phase 3 studies show that Bylvay was associated with sustained improvements in mean serum bile acids (sBA) and pruritus scores over time.
  • Overall, 84 patients received Bylvay during the pooled analysis period, and the overall median (range) exposure from the first dose of Bylvay was 53 (3−128) weeks.
  • sBA responders had larger improvements in pruritus than sBA non-responders or partial responders as defined by those who did not meet sBA response criteria reflecting either perceived treatment effects or patients with a partial sBA response (i.e., a sub-threshold reduction in sBAs).
  • Approximately 40% of patients met criteria for sBA response (≥70% reduction in sBAs or sBAs ≤70 μmol/L) during Bylvay treatment. When treatment response was defined by sBA and/or pruritus criteria (≥70% reduction in sBAs or sBAs ≤70 μmol/L), approximately 60% of patients treated with Bylvay achieved a treatment response. In addition, there are a number of patients that are partial responders.

• Bylvay Reduced Autotaxin, Pruritus and sBAs (oral presentation; session ID 2271): Autotaxin can be a marker of liver injury in cholestatic patients and elevated levels have been also associated with increased pruritus. Bylvay treatment reduced autotaxin, pruritus and sBAs with change or percent change from baseline to weeks 25 – 48 in patients with PFIC.
  • Results of this pooled analysis in children with PFIC from PEDFIC 1 and PEDFIC 2 studies show that Bylvay reduced autotaxin (-50%), pruritus (-1.4) and sBAs (-49%).
  • Significant correlations were observed between reductions in each pair of these parameters.

Evidence of Reducing Disease Burden, Improving Quality of Life

• Improvement in Hepatic Health, Sleep and Growth (poster #1951): Bylvay treatment for up to 72 weeks in patients with PFIC was associated with effects on hepatic parameters, growth and sleep.
  • Overall, 84 patients received Bylvay during the pooled analysis period, and the overall median (range) exposure from the first dose of Bylvay was 53 (3−128) weeks.
  • From baseline to week 72, responders had mean improvement in hepatic health parameters in transaminases and total bilirubin levels, quality of sleep and growth, with greater improvement observed in responders compared with non-responders.
  • sBA responders had large decreases in caregiver-reported percentage of days patients had scratching associated with bleeding, needed soothing and needed help falling asleep (–47%, –76%, –75%, respectively); increases or smaller changes were observed in sBA non-responders (3%, –24%, −35%, respectively).
  • Patients who were non-responders had more pronounced growth deficits at baseline; however, with treatment, mean height and weight Z scores increased in both responders and non-responders.
    
• Natural Variation in Clinical Signs and Symptoms (poster #1969): Prior to the start of PEDFIC 1, patients with PFIC1 and PFIC2 had considerable variations in sBAs and had variations in pruritus scores.
  • These data highlight that patients with PFIC experience natural fluctuations in clinical signs and symptoms because of their underlying disease. Before study start in the overall population, the median (range) of per-patient standard deviations across all pre-treatment measurements was 42 (5–183) μmol/L for sBAs and 0.6 (0–1.2) for pruritus scores.

Clinical Benefits Across PFIC Types

• Clinical Benefits of Bylvay in PFIC3 and PFIC6 (poster #1951): During up to 54 weeks of Bylvay treatment, patients with PFIC3 and PFIC6 experienced clinical benefits, including reductions in sBAs and improvement in pruritus symptoms, growth and sleep parameters.
  • Patients with PFIC3 and PFIC6 experienced mean reductions vs. baseline in sBAs (-91 mmol/L and -78 mmol/L, respectively) improvement in pruritus symptoms (-1.6 and -1.8, respectively), height (0.2 and 0.1, respectively), weight (0.1 and 0.5, respectively) and sleep parameters (-29 and -21, respectively), through week 36.

The observed safety and tolerability profile of Bylvay was consistent across studies, treatment groups and doses, regardless of PFIC classification or BSEP subtype. No drug-related serious adverse events were reported in either PEDFIC 1 or PEDFIC 2. Treatment-related diarrhea/frequent bowel movements reported in 9.5% of Bylvay treated patients in PEDFIC 1 and 5% of placebo-treated patients. Individual abstracts present data for specific safety and tolerability.

A2342 Preclinical Data in Viral Disease
The Company will also present data from its preclinical studies of A2342, the first oral NTCP inhibitor in development for viral and cholestatic liver diseases. IND-enabling studies for A2342 are currently being completed. Data to be presented is from studies on the impact of A2342 in models of in vitro and in vivo hepatitis B virus (HBV) infection and in animal models demonstrating NTCP target engagement. The first study (poster #837) aimed to investigate the antiviral efficacy of A2342 in vitro and in vivo, with the second study (poster #848) assessing the contribution of OATPs and identifying preclinical species to model NTCP inhibition in humans. Key findings from the A2342 preclinical studies include:

• Prevents HBV Entry In Vitro and Attenuates HBV Replication In Vivo: In vitro experiments demonstrated that A2342 displayed long-lasting inhibition of human NTCP bile acid transport activity and prevented HBV infection of human hepatocytes without affecting cell viability. A2342 also demonstrates good oral pharmacokinetics and attenuates HBV replication in humanized uPA/SCID mice in a dose-dependent manner.
• Induced Dose-Dependent Elevation of sBAs in Organic Anion Transporting Polypeptide (OATP) Knock Out (KO) Mice and Cynomolgus Monkeys: A2342 increased sBA levels in a dose-dependent manner in cynomolgus monkeys (3−30 mg/kg, n=2). Similar transient increases in sBAs have been observed in humans with SubQ NTCP inhibitors. This data thus provides excellent translational predictability to humans.

“It’s exciting to show the first data from our preclinical studies of A2342 that demonstrate activity in diseases like HBV. In addition, the NTCP engagement in non-human primates provides increased confidence in the translation of A2342 to humans,” said Ron Cooper, President and Chief Executive Officer of Albireo. “To be able to progress our entire pipeline in both the pediatric and adult liver programs demonstrates our ability to execute and create future value.”

Post-AASLD Conference Call
Albireo will host a post-AASLD conference call and live audio webcast on November 16 at 10:00am EST. Presenters will include Ron Cooper, President and Chief Executive Officer; Patrick Horn, M.D., Ph.D., Chief Medical Officer and Jan Mattsson, Ph.D., Chief Scientific Officer and Co-Founder. To access the live conference call by phone, please dial 877-407-0792 (domestic) or 201-689-8263 (international) and provide the access code 13724001. The virtual event will also be accessible from the Albireo Media and Investors page. To ensure a timely connection to the webcast, it is recommended that participants register at least 15 minutes prior to the scheduled start time. An archived version of the webcast will be available for replay in the Events & Presentations section of the Media & Investors page of Albireo’s website for two weeks following the event.

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). 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 for sale in Germany and will be available for sale in other European countries following pricing and reimbursement approval. A potent, once-daily, non-systemic ileal bile acid transport inhibitor, Bylvay 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 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 Alagille syndrome, 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 Alagille syndrome.

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 and biliary atresia, as well as an Open-label Extension (OLE) study for PFIC. In Europe, Bylvay has been approved for the treatment of PFIC and has been submitted for pricing and reimbursement approval. The Company has also initiated a Phase 1 clinical trial for A3907 to advance development in adult cholestatic liver disease, with IND-enabling studies moving ahead 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. The Boston Business Journal named Albireo one of the 2019 and 2020 Best Places to Work in Massachusetts. 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 and expectations for commercializing Bylvay in the U.S. and Europe; expectations about Bylvay’s acceptance by healthcare practitioners to treat PFIC patients; 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 pivotal trial for Bylvay in biliary atresia (BOLD), and the pivotal trial for Bylvay in Alagille syndrome (ASSERT); the Phase 1 trial for A3907; the target indication(s) for development or approval, the size, design, population, location, conduct, cost, objective, enrollment, duration or endpoints of any clinical trial, or 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, and the BOLD and ASSERT trials; discussions with the FDA or EMA regarding our programs; the potential benefits or competitive position of Bylvay or any other Albireo product candidate or program or the commercial opportunity in any target indication; the potential effects of Bylvay of the treatment of PFIC patients and its potential to improve the current standard of care; or the potential benefits of an orphan drug designation. 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: there are no guarantees that Bylvay will be commercially successful; we may encounter issues, delays or other challenges in launching or 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; results achieved in Bylvay in the treatment of patients with PFIC once we have launched the product may be different than observed in clinical trials, and may vary among patients; other 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 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 ASSERT, and the Phase 1 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, Company’s clinical trials; and Albireo’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
Lauren Sneider, 857-300-1737, lauren.sneider@albireopharma.com

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