Odevixibat in the Treatment of Progressive Familial Intrahepatic Cholestasis: A Systematic Literature Review for Brazilian's Health Technology Assessment
Author(s)
Melina Campagnaro, PhD1, Guilherme Marano, PharmD1, Vanessa Fabricio, MD, Msc2, Elenise Colletti, MBA3;
1IPSEN, Value Access & HEOR, São Paulo, Brazil, 2IPSEN, Medical Affairs, São Paulo, Brazil, 3IPSEN, Market Access & Public Affairs, São Paulo, Brazil
1IPSEN, Value Access & HEOR, São Paulo, Brazil, 2IPSEN, Medical Affairs, São Paulo, Brazil, 3IPSEN, Market Access & Public Affairs, São Paulo, Brazil
OBJECTIVES: Progressive familial intrahepatic cholestasis (PFIC) is a spectrum of rare, life-threatening genetic liver diseases that imposes significant burden on pediatric patients and their caregivers, severely impacting their quality of life. Depending on the severity of the disease, patients may face death or require liver transplantation from childhood to adolescence. As part of the Brazilian health technology assessment by Conitec of odevixibat (ODX) in patients with PFIC, a systematic literature review (SLR) was conducted to gather robust evidence of its efficacy and safety in this indication.
METHODS: EMBASE, MEDLINE, LILACS, PubMed, and Cochrane databases were searched for publications before September 2024. The SLR followed Conitec guidelines and only included randomized controlled trials (RCT).
RESULTS: Out of 358 identified publications, one study was included: a Phase III, double-blind, randomized, placebo-controlled, multicenter trial (PEDFIC1), evaluating the efficacy and safety of two dosages of ODX versus placebo over 24 weeks. Two primary endpoints were evaluated: (1) proportion of pruritus positive assessment, was significantly higher with ODX (55%) versus placebo (30%), with a mean difference of 25% [95% CI 8.5−41.5]; p=0.0038); (2) Proportion of patients with serum bile acid (sBA) response, was significantly higher with ODX (33%) vs placebo (0%), with a mean difference of 30.7% [95% CI 12.6−48.8; p=0.0030]). Secondary endpoints on sleep parameters also showed benefits of ODX over placebo. Most common adverse events were diarrhea or frequent bowel movements and fever.
CONCLUSIONS: One RCT demonstrated that ODX was an effective and well tolerated treatment in patients with PFIC, reducing pruritus and sBA over 24 weeks. Additional non-RCT evidence of long-term efficacy of ODX have also been published but are not included in this SLR, namely the results of the extension trial PEDFIC2, an open label, single-arm, 72-week study in patients with PFIC, showing sustained efficacy over time.
METHODS: EMBASE, MEDLINE, LILACS, PubMed, and Cochrane databases were searched for publications before September 2024. The SLR followed Conitec guidelines and only included randomized controlled trials (RCT).
RESULTS: Out of 358 identified publications, one study was included: a Phase III, double-blind, randomized, placebo-controlled, multicenter trial (PEDFIC1), evaluating the efficacy and safety of two dosages of ODX versus placebo over 24 weeks. Two primary endpoints were evaluated: (1) proportion of pruritus positive assessment, was significantly higher with ODX (55%) versus placebo (30%), with a mean difference of 25% [95% CI 8.5−41.5]; p=0.0038); (2) Proportion of patients with serum bile acid (sBA) response, was significantly higher with ODX (33%) vs placebo (0%), with a mean difference of 30.7% [95% CI 12.6−48.8; p=0.0030]). Secondary endpoints on sleep parameters also showed benefits of ODX over placebo. Most common adverse events were diarrhea or frequent bowel movements and fever.
CONCLUSIONS: One RCT demonstrated that ODX was an effective and well tolerated treatment in patients with PFIC, reducing pruritus and sBA over 24 weeks. Additional non-RCT evidence of long-term efficacy of ODX have also been published but are not included in this SLR, namely the results of the extension trial PEDFIC2, an open label, single-arm, 72-week study in patients with PFIC, showing sustained efficacy over time.
Conference/Value in Health Info
2025-05, ISPOR 2025, Montréal, Quebec, CA
Value in Health, Volume 28, Issue S1
Code
HTA37
Topic
Health Technology Assessment
Disease
SDC: Gastrointestinal Disorders, SDC: Pediatrics, SDC: Rare & Orphan Diseases