Breakthrough drug for cholestasis! Phase III of the potent ileal bile acid transporter inhibitor odevixibat succeeded: reaching the European and American regulatory endpoint!

September 09, 2020 // -- Albireo Pharma is a company that develops a new bile acid regulator for rare childhood liver disease in the clinical phase.
recently, the company announced positive results in a global Phase 3 PEDFIC-1 clinical study evaluating odevixibat treatment for in-hepatic bile siltation (PFIC).
this is the largest study ever conducted in patients with PFIC Type 1 (PFIC1) and Type 2 (PFIC2).
results showed that the study reached two main endpoints: odevixibat significantly reduced bile acid response (SBA, p-0.003), significantly improved skin itching (p-0.004), and had a single-digit diarrhea rate compared to placebo.
odevixibat is a pioneering, powerful selective, non-systematic, refoural bile acid transporter (IBAT) inhibitor with minimal systemic exposure and local function in the intestines.
, the drug is being developed for the treatment of rare children with bile siltation liver disease, the first target adaptation is PPIC.
PFIC is a devastating disease and many patients have a liver transplant or other invasive surgery.
positive results from the PEDFIC-1 study represent an important milestone in confirming that odevixibat is a safe and effective treatment that has the potential to make a real difference for PFIC patients and their families.
has the potential to become the first drug to be approved for the treatment of PPICs.
Albireo plans to complete regulatory submissions in the European Union and the United States by 2021 and bring the drug to market in the second half of 2021 after approval.
odevixibat chemical structure (photo source: medkoo.com) PEDFIC-1 was a randomized, double-blind, placebo-controlled, global multi-center Phase 3 study conducted in 62 patients aged 6 months to 15.9 years of age PFIC1 or PFIC2.
, patients were randomly assigned to receive 2 oral doses of odevixibat commercial preparations (40 μg/kg/day, 120μg/kg/day) or placebo for 24 weeks at a time.
the odevixibat treatment group receive oral capsules or sprays once a day, and these two preparations do not need to be refrigerated.
data showed that in the main analysis, the study reached the main endpoint of compliance with U.S. regulation: a positive rate of 53.5 percent for itching in the odevixibat treatment group and 28.7 percent in the placebo group (p-0.004). in terms of
secondary endpoints, 42.9% of patients in the odevixibat treatment group had a clinically significant improvement in itching scores (defined as: on the 0-4 scale, the itching score for week 24 decreased from the baseline level by 1.0 points), and the placebo group had a 10.5% (p-0.018).
addition, the study reached the main endpoint in line with EU regulation: 33.3% of patients in the odevixibat treatment group had a 70% reduction in serum bile acid (sBA) or a level of 70μmol/L, and no patients in the placebo group met this goal (p-0.003).
secondary endpoint, the average reduction of bile acid in the odevixibat treatment group was 114.3 μmol/L, and the placebo group was increased by 13.1μmol/L (p=0.002).
two doses of odevixibat are statistically significant at each endpoint.
studies, odevixibat has good tolerance.
the rate of adverse events was similar to that of placebos.
no serious adverse drug-related events (SAEs) were reported during the study.
diarrhea/frequent platoons were the most common treatment-related gastrointestinal adverse events, occurring at 9.5 per cent in patients treated with odevixibat and 5.0 per cent in the placebo group.
results of the study will be presented at a future scientific conference.
Cooper, President and CEO of Albireo, said: "The successful clinical application of IBAT inhibitors is entirely based on the ability to reduce bile acid and reduce diarrhoea rates.
odevixibat reduced bile acid in patients with PFIC1 and PXI2 and demonstrated the clinical significance of itching.
this is exciting news for children with PPICs, who may soon have an easy-to-use, daily drug to treat life-threatening liver disease if odevixibat is approved.
strong results from the PEDFIC-1 study have increased our confidence in the ongoing trial of the critical BOLD trial for the treatment of bile canal latching and the Alagille syndrome study planned for later this year.
Richard Thompson, lead investigator on the study and professor of molecular hepatology at King's College London, said: "The results of the PEDFIC-1 Phase 3 study represent the potential for a paradigm shift in PPIC treatment.
these data show that odevixibat reduces serum bile acid and improves itching in PFIC patients.
coupled with the good safety and toerability demonstrated by odevixibat, these data highlight the potential for improvements based on existing standards of care, which typically include non-label medications or invasive procedures, including transplantation.
" () Original origin: Albireo Phase 3 Trial Meets Both Primary Endpoints for Odevixibat in PFIC.