Ipsen announced data at the AASLD meeting assessing the long-term efficacy and safety of patients treated with Bylvay (odevixibat) from two Phase III open-label extension studies.

Sustained efficacy data and improvements in height, weight and sleep measures were observed for patients treated with Bylvay for at least 72 weeks in both rare cholestatic diseases.

“We know from our work with patient communities that receiving a diagnosis of PFIC and ALGS can be overwhelming in a patient or caregivers’ life. Disease symptoms like severe itch can have an impact on the whole family,” said Sandra Silvestri, EVP Chief Medical Officer, Ipsen. “Data suggesting Bylvay-treated patients experienced sustained efficacy, and which support the safety and tolerability profile seen in previous clinical trials, are important. Ipsen is committed to being the leader across rare cholestatic liver diseases and we are just getting started.”

PEDFIC 2 Study in PFIC; “These open-label extension data from PEDFIC 2 suggest that the initial reduction in pruritus and in serum bile acid levels achieved following initiation of odevixibat are being sustained into the longer term,” said Dr. Richard J. Thompson, Professor of Molecular Hepatology, King’s College London and principal investigator of the PEDFIC 2 trial. “We are also observing reductions in both pruritus and serum bile acid across a number of PFIC subtypes. This is important information for our understanding of the therapeutic management of our patients living with PFIC.”

 PEDFIC 2 was an open-label extension study (n=116; patients from PEDFIC 1 Bylvay and placebo cohorts at week 24, and new Bylvay-naïve patients of any age and PFIC subtype), evaluating the efficacy and safety of Bylvay through 72 weeks (n=83). The data showed a clinically meaningful 1-point reduction in pruritus score at week 72 in 42 percent of patients <18 years old with PFIC 1 and 2 who transitioned to Bylvay at 24 weeks (n=5/12) and 61 percent of patients with any type of PFIC and of any age excluding episodic (n=19/31). Rapid initial pruritus scores achieved by week 4 were sustained for patients who remained on treatment. At 72 weeks, the mean change in serum bile acid (sBA) levels from patients who transition to Bylvay at week 24 (n=15) was –104.00 µmol/L and Bylvay-treated patients (n=43) was -57.97 µmol/L .

 Beyond the clinically meaningful and sustained improvements seen in pruritus and sBA levels, height, weight and sleep increases were reported at 72 weeks in Bylvay-treated patients. Most adverse events in Bylvay-treated patients over the duration of the study were reported as mild or moderate. The most common were gastrointestinal (17.2 percent; n=20/116), including diarrhea (12 percent; n=14/116). In two cases, diarrhea led to one treatment interruption and one discontinuation.

 Assert-EXT Study in ALGS; “The sustained improvements we've seen in Bylvay-treated individuals living with Alagille syndrome are encouraging,” said Dr. Nadia Ovchinsky, Chief, Division of Gastroenterology and Hepatology, Hassenfeld Children's Hospital at NYU Langone, New York. and principal investigator of the ASSERT trial. “These results not only show the potential to manage symptoms like pruritus, which can be extremely difficult for children and their parents to manage, but we’re also seeing a consistent safety profile over the longer term with sustained tolerability.”

 In ASSERT-EXT, the open-label extension study (n=50) evaluating the long-term efficacy and safety of Bylvay in ALGS patients (ages 1-15.9 years) through 72 weeks (n=44), sustained improvements were observed in pruritus and sBA levels through 72 weeks . At week 72, 93 percent (n=28/30) of patients who received Bylvay throughout the 24 weeks ASSERT trial and 77 percent (n=10/13) of those who transitioned from placebo to Bylvay at week 24 experienced a clinically meaningful ≥1 point reduction in pruritus score. Reductions in sBA levels were also observed in patients treated with Bylvay for 72 weeks showing a mean reduction of 124 µmol/L in those who continuously received Bylvay and a mean reduction of 139 µmol/L in patients who transitioned from placebo to Bylvay. Mean changes from baseline were observed in height (8.2 cm) and weight (2.8 kg) on continuous Bylvay use and for patients who transitioned from placebo to Bylvay, height (10.7 cm) and weight (3.3 kg) mean changes were also reported. 

Improvements in sleep were observed from weeks 24 to 72 across all four sleep parameters (n=43), including proportion of days seeing blood due to scratching, proportion of days needing help falling asleep, proportion of days needing soothing and daytime tiredness. Data supports the safety profile in the ASSERT clinical trial for Bylvay. Treatment emergent adverse event (TEAE) occurred in 18 percent (n=6/33) of patients who continuously received Bylvay and 41 percent (n=7/17) of patients who transitioned from placebo to Bylvay. Most adverse events were mild or moderate with diarrhea as the most common TEAE. One TEAE led to discontinuation.

About PFIC and ALGS; PFIC is a group of rare genetic disorders in which bile acids build up in the liver, causing damage, which may result in liver failure. ALGS is also a rare genetic disorder, affecting multiple organs including the liver, heart, skeleton, eyes and kidneys. Without early diagnosis and effective management, people living with PFIC and ALGS may need a liver transplant. Debilitating itch, caused as a result of the serum bile acid build up, is one of the most common symptoms of both PFIC and ALGS, significantly impacting sleep and daily activities and resulting in skin mutilation, loss of sleep, irritability, and poor attention.