Benzinga | Dec 16, 2021 08:37AM EST

Albireo Announces Topline Data From Phase 1 Study Of A3907; Says Study Achieved Both Primary And Secondary Objectives, Was Safe And Well Tolerated

-- First oral, systemic ASBT inhibitor was safe and well tolerated



-- Secondary and exploratory objectives show favorable pharmacokinetics and systemic exposure, while providing target engagement signals

-- Company on track to initiate planned adult liver disease Phase 2 study in 2022

BOSTON, Dec. 16, 2021 (GLOBE NEWSWIRE) -- Albireo Pharma, Inc. (NASDAQ:ALBO), a rare liver disease company developing novel bile acid modulators, today announced positive topline results from its Phase 1 clinical trial of A3907, the first oral systemic apical sodium-dependent bile acid transporter (ASBT) inhibitor. The study achieved both primary and secondary objectives. Phase 1 study is a first-in-human, double-blind, single and multiple ascending dose study in healthy adult subjects to investigate the safety, tolerability, pharmacokinetics of orally administered A3907. A3907 was safe and well tolerated in this study at systemic exposures that demonstrated therapeutic benefits in preclinical models. With the potential to inhibit ileal, renal and hepatic ASBT, A3907 could provide the optimal balance of efficacy and tolerability in patients in multiple liver diseases.

The study met its primary objectives with data showing A3907 overall to be safe and well tolerated, with no serious adverse events (SAEs) or discontinuations due to treatment emergent adverse events (TEAEs). All TEAEs were mild, the most common were mainly abdominal symptoms such as loose stools, and all participants finished the trial protocol. No clinically significant effects in clinical chemistry, hematology, physical examinations or ECG. The study also met its secondary objectives with dose-related plasma exposure up to 81 mg dose, with no accumulation. Exposure levels were within the range that show effects in animal disease models. Single doses of A3907 showed dose proportional increases in plasma exposure up to 81 mg with no further increase at a dose of 162 mg. The study showed target engagement with 7alpha-hydroxy-4-cholesten-3-one (C4) increases and low-density lipoprotein cholesterol (LDL-C) reductions, with C4 increases indicating elevation in bile acid excretion, while LDL-C reduction indicating elevated synthesis of bile acids from cholesterol.

"The results from our Phase 1 study of A3907 show that the drug candidate is safe and well tolerated with favorable pharmacokinetics and high systemic exposure, giving us the greenlight to advance to a Phase 2 study," said Jan Mattsson, Chief Scientific Officer of Albireo. "These results represent an exciting milestone in the development of this next generation bile acid modulators as we could potentially be offering physicians new treatments to treat liver diseases that could increase efficacy without sacrificing tolerability for patients."

The Phase 1 trial was a randomized, double-blind, placebo-controlled, single and seven day multiple-dose study was conducted in 54 and 22, respectively, healthy subjects. Doses evaluated were 1-162 mg in the single ascending dose portion, and 9-67.5 mg in the multiple ascending dose portion. Primary objectives were safety and tolerability, secondary objectives were evaluation of pharmacokinetics, and there were multiple exploratory endpoints.