ASSERT1,3
Double-blind, randomized, placebo-controlled
32
sites
13
countries
participated
Bylvay
120 mcg/kg/day
(n=35)
Placebo
(n=17)
Randomization 2:1
(N=52)
24 weeks
Primary endpoint2
Change from baseline in average scratching score to month 6 (weeks 21 to 24)†
Secondary endpoints included2
- Change from baseline in serum bile acid (sBA) levels through week 24
- Proportion of participants achieving a clinically meaningful decrease in pruritus
- Change from baseline in sleep parameters through week 24‡
ASSERT-EXT1,4,5
Open-label extension*
21
sites
10
countries
participated
COHORT 1A
Bylvay 
Bylvay
120 mcg/kg/day
(n=32)
COHORT 1B
Placebo Bylvay
120 mcg/kg/day
(n=17)
72 weeks
COHORT 2 (actively enrolling)
Bylvay 120 mcg/kg/day
12 weeks
Primary endpoint6
Change from baseline in average scratching score through week 72†
Secondary endpoints included6
- Change from baseline in sBA levels through week 72
- Change from baseline in sleep parameters through week 72‡
Enrolled participants were 6 months to 15 years of age with1
- Genetically confirmed Alagille syndrome diagnosis1,2
- History of significant pruritus2
- Elevated sBA levels2
Concomitant ursodeoxycholic acid (UDCA) and other antipruritic medications were permitted, provided they were at a stable dose at least 4 weeks before enrollment with no dosage changes planned during study period.2,6,7
ASSERT is the only pivotal study of an IBAT inhibitor in Alagille syndrome to enroll participants with1,2
- JAG1 mutation (92%; n/N=48/52) or
- NOTCH2 mutation (8%; n/N=4/52)
Concomitant ursodeoxycholic acid (UDCA) and other antipruritic medications were permitted, provided they were at a stable dose at least 4 weeks before enrollment with no dosage changes planned during study period.2,6,7
- *ASSERT-EXT is an open-label, long-term safety and efficacy trial in participants with Alagille syndrome. This trial enrolled 2 groups of participants, Cohort 1 (participants who participated in ASSERT, n=49) and Cohort 2 (infants under 12 months of age) with Alagille syndrome. During ASSERT-EXT, all participants receive Bylvay 120 mcg/kg/day, and the treatment duration is either 72 weeks (Cohort 1) or 12 weeks (Cohort 2). Interim data from ASSERT-EXT Cohort 1 was presented and is captured here.4
- †Change from baseline as measured by the PRUCISION™ ObsRO scale, a validated instrument that defines a ≥1-point reduction as a clinically meaningful change in pruritus score.8
- ‡Data reported using the PRUCISION™ ObsRO instrument; caregivers answered 7 questions about the effects that itch had on their child’s sleep and sleep-related parameters daily.2,6,7
In the ASSERT and ASSERT-EXT trials,
Cholestatic pruritus was measured using the PRUCISION™ ObsRO scale1,8
- A validated 5-point scale from 0 (“No scratching”) to 4 (“Worst possible scratching”)1,8
- Scratching scores were recorded twice daily by a caregiver1,8
- All participants had medium or worse scratching at baseline (ObsRO score ≥2)1,8
The PRUCISION™ ObsRO scale is a validated instrument that defines a ≥1-point reduction as a clinically meaningful change in pruritus score8
Consider how a reduction in cholestatic pruritus could impact your patients with Alagille syndrome
IBAT=ileal bile acid transporter; ObsRO=observer-reported outcomes.
References:
- Bylvay Prescribing Information. Cambridge, MA: Ipsen Biopharmaceuticals, Inc.; 2024.
- Ovchinsky N, Aumar M, Baker A, et al. Efficacy and safety of odevixibat in patients with Alagille syndrome (ASSERT): a phase 3, double-blind, randomised, placebo-controlled trial. Lancet Gastroenterol Hepatol. 2024;9(7):632-645.
- ClinicalTrials.gov. A phase 3 double-blind, randomized, placebo-controlled study of the safety and efficacy of odevixibat (A4250) in patients with Alagille syndrome (ASSERT). NCT04674761. Updated April 10, 2023. Accessed April 24, 2023.
- ClinicalTrials.gov. An open-label study to evaluate the long-term safety and efficacy of odevixibat (A4250) in patients with Alagille syndrome (ASSERT-EXT). NCT05035030. Updated October 1, 2024. Accessed October 29, 2024.
- Ovchinsky N, Aumar M, Baker A, et al. Efficacy and safety of odevixibat in patients with Alagille syndrome: interim results from the open-label, phase 3 ASSERT-EXT study. Presented at: 55th Annual Meeting of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition; May 17-20, 2023; Vienna, Austria.
- Data on file A4250-015. November 11, 2022. Boston, MA: Albireo Pharma, Inc.
- Data on file A4250-012. November 10, 2022. Boston, MA: Albireo Pharma, Inc.
- Gwaltney C, Ivanescu C, Karlsson L, Warholic N, Kjems L, Horn P. Validation of the PRUCISION instruments in pediatric patients with progressive familial intrahepatic cholestasis. Adv Ther. 2022;39(11):5105-5125.