{"id":42972,"date":"2024-11-18T07:00:00","date_gmt":"2024-11-18T06:00:00","guid":{"rendered":"https:\/\/www.ipsen.com\/us\/press-releases\/bylvay-odevixibat-data-shows-sustained-improvement-in-severe-itch-and-serum-bile-acid-levels-in-patients-with-pfic-and-algs-2982434\/"},"modified":"2024-11-18T07:00:00","modified_gmt":"2024-11-18T06:00:00","slug":"bylvay-odevixibat-data-shows-sustained-improvement-in-severe-itch-and-serum-bile-acid-levels-in-patients-with-pfic-and-algs-2982434","status":"publish","type":"press_release","link":"https:\/\/www.ipsen.com\/us\/press-releases\/bylvay-odevixibat-data-shows-sustained-improvement-in-severe-itch-and-serum-bile-acid-levels-in-patients-with-pfic-and-algs-2982434\/","title":{"rendered":"Bylvay\u00ae (odevixibat) data shows sustained improvement in severe itch and serum bile acid levels in patients with PFIC and ALGS"},"content":{"rendered":"
PARIS, FRANCE, 18 November, 2024 <\/strong>Ipsen (Euronext: IPN; ADR: IPSEY) today announced data at the American Association for the Study of Liver Diseases (AASLD) assessing the long-term efficacy and safety of patients treated with Bylvay\u00ae<\/em><\/strong><\/sup> from two Phase III open-label extension studies: late-breaking abstract (#5045) on PEDFIC 2 in Progressive Familial Intrahepatic Cholestasis (PFIC) and oral presentation ASSERT-EXT (#50) in Alagille syndrome (ALGS). 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.<\/p>\n \u201cWe know from our work with patient communities that receiving a diagnosis of PFIC and ALGS can be overwhelming in a patient or caregivers\u2019 life. Disease symptoms like severe itch can have an impact on the whole family,\u201d said Sandra Silvestri, EVP Chief Medical Officer, Ipsen. \u201cData 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.\u201d<\/p>\n PEDFIC 2 Study in PFIC<\/em><\/strong><\/p>\n \u201cThese 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,\u201d said Dr. Richard J. Thompson, Professor of Molecular Hepatology, King\u2019s College London and principal investigator of the PEDFIC 2 trial. \u201cWe 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.\u201d <\/p>\n PEDFIC 2 was an open-label extension study (n=116; patients from PEDFIC 1 Bylvay and placebo cohorts at week 24, and new Bylvay-na\u00efve patients of any age and PFIC subtype), evaluating the efficacy and safety of Bylvay through 72 weeks (n=83).1<\/em><\/strong><\/sup> 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 \u2013104.00 \u00b5mol\/L and Bylvay-treated patients (n=43) was -57.97 \u00b5mol\/L . <\/p>\n 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.<\/p>\n Assert-EXT Study in ALGS<\/em><\/strong> 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.2<\/sup> 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 \u22651 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 \u00b5mol\/L in those who continuously received Bylvay and a mean reduction of 139 \u00b5mol\/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. <\/p>\n 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.<\/p>\n About PFIC and ALGS<\/em><\/strong> Bylvay (odevixibat) posters presented at AASLD<\/em><\/strong><\/p>\n \u00a0<\/p>\n \u00a0 <\/td>\n \u00a0 <\/td>\n \u00a0<\/p>\n Phase I <\/strong> \u00a0<\/p>\n \u00a0<\/p>\n Poster, Abstract [4280]<\/em> \u00a0<\/p>\n A Phase 1, open-label, fixed-sequence, crossover study to evaluate the interaction of multiple-dose odevixibat with the pharmacokinetics of single-dose combined oral contraceptive steroids in healthy female participants<\/p>\n \u00a0<\/p>\n \u00a0 <\/td>\n \u00a0<\/p>\n \u00a0<\/p>\n Florent Mazuir et al.<\/strong> <\/td>\n<\/tr>\n About Bylvay (odevixibat)<\/em><\/strong> Odevixibat was also approved in June 2021 in the E.U. under the brand name Bylvay\u00ae<\/sup>, as the first drug treatment option for all types of PFIC in patients aged 6 months or older. Bylvay has received orphan exclusivity for the treatment of PFIC in the U.S. and E.U. <\/p>\n In June 2023 Bylvay was approved in the U.S. for the treatment of cholestatic pruritus in patients from 12 months of age with Alagille syndrome (ALGS) and received orphan exclusivity for ALGS. In September 2024, odevixibat was approved in the E.U under the brand name Kayfanda\u00ae<\/sup> for the treatment of cholestatic pruritus in ALGS in patients aged 6 months or older.<\/p>\n IMPORTANT SAFETY INFORMATION \u2013 U.S.<\/strong> Liver Test Abnormalities<\/strong> Obtain baseline liver tests and monitor during treatment. Dose reduction or treatment interruption\u00a0may be required if abnormalities occur. For persistent or recurrent liver test abnormalities, consider treatment discontinuation.<\/p>\n Permanently discontinue Bylvay if a patient progresses to portal hypertension or experiences a\u00a0hepatic decompensation event.<\/p>\n Diarrhea<\/strong> Fat-Soluble Vitamin (FSV) Deficiency<\/strong> Obtain baseline levels and monitor during treatment, along with any clinical manifestations.\u00a0Supplement if deficiency is observed. If FSV deficiency persists or worsens despite FSV supplementation, discontinue treatment.<\/p>\n ADVERSE REACTIONS<\/strong> DRUG INTERACTIONS<\/strong> USE IN SPECIFIC POPULATIONS<\/strong> There is a pregnancy safety study that monitors pregnancy outcomes in women exposed to BYLVAY\u00a0during pregnancy. Pregnant women exposed to BYLVAY, or their healthcare providers, should report\u00a0BYLVAY exposure by calling 1-855-463-5127.<\/p>\n To report SUSPECTED ADVERSE REACTIONS, contact Ipsen Biopharmaceuticals, Inc. at +1-855-463-5127, or FDA at 1-800-FDA-1088 or www.fda.gov\/medwatch.<\/strong><\/p>\n Indications and Usage U.S.<\/strong> Limitation of use<\/strong> Please see full U.S.\u00a0<\/strong>Prescribing Information<\/strong><\/a>.<\/strong><\/p>\n Indications of use E.U.<\/strong>
\u201cThe sustained improvements we’ve seen in Bylvay-treated individuals living with Alagille syndrome are encouraging,\u201d said Dr. Nadia Ovchinsky, Chief, Division of Gastroenterology and\u00a0Hepatology, Hassenfeld Children’s Hospital at NYU Langone, New York. and principal investigator of the ASSERT trial. \u201cThese 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\u2019re also seeing a consistent safety profile over the longer term with sustained tolerability.\u201d<\/p>\n
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.<\/p>\n\n
\n Abstract<\/strong> <\/td>\n Poster or Oral #<\/strong> <\/td>\n Full title<\/strong> <\/td>\n Authors\u00a0<\/strong> <\/td>\n<\/tr>\n \n ASSERT-EXT <\/strong>
final results<\/strong> <\/td>\n Oral, Abstract Parallel, ePoster [50]<\/em>
Monday 18 November <\/strong>
11:45\u201312:00
Human Cholestatic, PBC and other Biliary Disorders in Children and Adults<\/p>\n ASSERT-EXT: Final data from an open-label, Phase 3 study of odevixibat in patients with Alagille syndrome <\/td>\n Nadia Ovchinsky et al.<\/strong> <\/td>\n<\/tr>\n \n Hepatic\u00a0<\/strong>
parameters\u00a0with\u00a0<\/strong>
ODX in PFIC<\/strong> <\/td>\n Poster, Abstract [4277]<\/em>
Monday 18 November<\/strong>
13:00\u201314:00
Poster Session IV <\/td>\n Effects of odevixibat vs placebo on hepatic biochemical parameters and liver adverse events in patients with PFIC:
Data from the PEDFIC 1 study<\/p>\n Tassos Grammatikopoulos et al. <\/strong> <\/td>\n<\/tr>\n \n \u00a0<\/p>\n
DDI results<\/strong> <\/td>\n \u00a0<\/p>\n
Monday 18 November<\/strong>
13:00\u201314:00
Poster Session IV <\/td>\n \u00a0<\/p>\n \u00a0<\/p>\n \n \u00a0 <\/td>\n \u00a0 <\/td>\n \u00a0 <\/td>\n \u00a0 <\/td>\n<\/tr>\n \n PEDFIC1\/2 OLE final results (LB)<\/strong> <\/td>\n Poster, Abstract [5045]<\/em>
Monday 18 November<\/strong>
13:00\u201314:00
Poster Session IV <\/td>\n Sustained, long-term efficacy and safety of odevixibat in patients with progressive familial intrahepatic cholestasis: Results from the PEDFIC2 Phase 3, open-label extension study <\/td>\n Richard Thompson et al.<\/strong> <\/td>\n<\/tr>\n<\/table>\n
Odevixibat is a once-daily non-systemic ileal bile acid transport (IBAT) inhibitor approved under the brand name Bylvay\u00ae<\/sup> in the U.S. as the first drug treatment option for patients 3 months of age and older living with cholestatic pruritus due to progressive familial intrahepatic cholestasis (PFIC). BYLVAY may not be effective in a subgroup of PFIC type 2 patients with specific ABCB11 <\/em>variants resulting in non-functional or complete absence of the bile salt export pump protein.<\/p>\n
Warnings and Precautions:<\/strong><\/p>\n
Patients who enrolled in PFIC and ALGS clinical trials had abnormal liver tests at baseline. In clinical\u00a0trials, treatment-emergent elevations of liver tests or worsening of liver tests relative to baseline values were observed. Most abnormalities included elevations in aspartate aminotransferase (AST), alanine transaminase (ALT) in PFIC and ALGS, and total and direct bilirubin in PFIC clinical trials. No patients permanently discontinued treatment due to liver test abnormalities.<\/p>\n
Diarrhea occurred in both PFIC and ALGS clinical trials in BYLVAY-treated patients at a rate greater than\u00a0placebo treated patients. If diarrhea occurs with use of BYLVAY, monitor for dehydration and treat promptly. Treatment interruption or discontinuation may be required for persistent diarrhea with no alternate etiology.<\/p>\n
Fat-soluble vitamins (FSV) include vitamin A, D, E, and K. PFIC and ALGS patients can have FSV\u00a0deficiency at baseline, as part of their disease. BYLVAY may affect absorption of fat-soluble vitamins.<\/p>\n
ALGS:<\/strong> The most common adverse reactions (>5%) are diarrhea, abdominal pain, hematoma, and\u00a0decreased weight.
PFIC:<\/strong> The most common adverse reactions (>2%) are diarrhea, liver test abnormalities, vomiting,\u00a0abdominal pain, and fat-soluble vitamin deficiency.<\/p>\n
For patients taking bile acid binding resins, take BYLVAY at least 4 hours before or 4 hours after\u00a0administering, as bile acid binding resins may bind to and reduce BYLVAY efficacy.<\/p>\n
There are no human data on BYLVAY use in pregnant persons to establish a drug-associated risk of\u00a0major birth defects, miscarriage, or adverse developmental outcomes. Based on findings from animal reproduction studies, BYLVAY may cause cardiac malformations when a fetus is exposed during pregnancy.<\/p>\n
Bylvay is an ileal bile acid transporter (IBAT) inhibitor indicated for the treatment of cholestatic pruritus in:
Patients 12 months of age and older with Alagille syndrome (ALGS)
Patients 3 months of age and older with progressive familial intrahepatic cholestasis (PFIC)<\/p>\n
Bylvay may not be effective in a subgroup of PFIC type 2 patients with specific ABCB11 variants resulting in non-functional or complete absence of the bile salt export pump protein<\/p>\n
Bylvay is indicated for the treatment of progressive familial intrahepatic cholestasis (PFIC) in patients aged 6 months or older. Please see full E.U.<\/strong>\u00a0Prescribing Information<\/strong><\/a>.<\/strong><\/p>\n