Summary

Recommendation

The Canadian Drug Expert Committee (CDEC) recommends that odevixibat be reimbursed for the treatment of pruritus in patients aged 6 months or older with progressive familial intrahepatic cholestasis (PFIC) only if the conditions listed in Table 1 are met.

Rationale for the Recommendation

CDEC recognized the rarity of PFIC and the unmet need of patients with this disease who experience severe pruritis. Results from 1 phase III, double-blind, randomized, placebo-controlled trial (PEDFIC 1; N = 62) demonstrated that, compared to placebo, treatment with odevixibat (40 mcg/kg per day and 120 mcg/kg per day) improves pruritus based on the PRUCISION observer-reported (ObsRO) instrument for patients with PFIC type 1 (PFIC1) and PFIC type 2 (PFIC2). The proportion of patients with a pruritus response based on the ObsRO instrument at week 24 was a primary efficacy end point in the regulatory submission to the US FDA. Compared with placebo (n = 20), the least squares mean difference in the proportion of patients who experienced a response in pruritis with odevixibat at 24 weeks was 28.23% (95% confidence interval [CI], 9.83% to 46.64%) for the 40 mcg/kg per day dose (n = 23) and 21.71% (95% CI, 1.87% to 41.54%) for the 120 mcg/kg per day dose (n = 19).

Patients identified a need for effective treatments for PFIC that reduce pruritis, delay the course of the disease, avoid or delay the need for surgery or liver transplant, and improve health-related quality of life (HRQoL). CDEC concluded that odevixibat may provide an effective treatment for pruritis. Pruritis may affect sleep, eating, growth, and patients’ and caregivers’ quality of life, although the evidence is uncertain about the effects of odevixibat on these outcomes due to imprecision in results of the PEDFIC 1 trial.

Using the sponsor-submitted price for odevixibat and publicly listed prices for all other drug costs, the incremental cost-effectiveness ratio (ICER) for odevixibat plus standard of care was $3,462,139 per quality-adjusted life-year (QALY) gained compared with standard of care alone. At this ICER, odevixibat is not cost-effective at a willingness-to-pay (WTP) threshold of $50,000 per QALY for the treatment of pruritus in patients aged 6 months or older with PFIC. A price reduction is required for odevixibat to be considered cost-effective at a WTP threshold of $50,000 per QALY.

Table 1

Reimbursement Conditions and Reasons.

Discussion Points

• Unmet needs: Due to the uncertainty associated with the submitted evidence, CDEC deliberated on odevixibat considering the criteria for significant unmet needs described in section 9.3.1 of the Procedures for CADTH Reimbursement Reviews. CDEC noted that PFIC is a rare and severe disease associated with morbidity and mortality. Furthermore, families and clinical experts agreed that the current treatment options for severe pruritis associated with PFIC are limited. Considering the rarity of PFIC and unmet need of this patient population, CDEC concluded that odevixibat has the potential to reduce morbidity associated with PFIC, although the available evidence is associated with uncertainty.
• PFIC subtypes: CDEC noted that the PEDFIC 1 trial enrolled patients with PFIC1 and PFIC2, and that a limited number of patients with other subtypes of PFIC were included in the extension phase of the PEDFIC 1 trial and in the PEDFIC 2 trial. Given that the approved indication does not restrict the use of odevixibat to any PFIC subtype, CDEC discussed the generalizability of the evidence in other PFIC subtypes. CDEC indicated that evidence-based practice would limit prescribing of odevixibat to only PFIC subtypes 1 and 2.
• Serum bile acid (sBA) levels: CDEC noted that the PEDFIC 1 trial was designed with 2 different primary end points (sBA level and pruritis) to meet regulatory requirements in multiple jurisdictions. The proportion of patients who experienced an sBA response was the primary outcome of the PEDFIC 1 trial for jurisdictions outside of the US, and the only outcome controlled for multiplicity. The PEDFIC 1 trial met this end point, as the adjusted difference in proportions of patients experiencing at least a 70% reduction in sBA levels from baseline to end of treatment or reaching a level of 70 μmol/L or less after 24 weeks between odevixibat 40 mcg/kg per day and placebo was 44.1% (95% CI, 23.6% to 64.6%; P = 0.0015) and between odevixibat 120 mcg/kg per day and placebo was 21.6% (95% CI, −0.5% to 43.8%; P = 0.0174). However, CDEC noted that pruritus and disease progression (i.e., need for surgical biliary diversion [SBD] or liver transplant, mortality) are more important outcomes to patients and clinicians. CDEC discussed that the relationship between sBA levels, disease progression, and pruritus has not been established.
• Extension study: CDEC considered evidence from PEDFIC 2, an ongoing phase III, nonrandomized, open-label extension study to investigate the long-term efficacy and safety of a 120 mcg/kg daily dose of odevixibat in patients with PFIC. However, the PEDFIC 2 study was limited by its open-label and noncomparative design. Some patients who received odevixibat at a dosage of 40 mcg/kg per day in the PEDFIC 1 trial received odevixibat at a dosage of 120 mcg/kg per day in the PEDFIC 2 trial. The sponsor reported that the percentage of patients who had a positive pruritis response increased in those who transitioned from 40 mcg/kg per day to 120 mcg/kg per day from PEDFIC 1 to PEDFIC 2 (||||| ||||| || ||||| || ||||| ||||| || ||||||| ||||||| ||||| ||| |||| ||||||||| || ||||||||| ||| || |||||||| || |||||||| ||| ||||||||| || ||| ||| |||||||||| |||| |||||||| ||||||||||| ||||| || ||||| || ||||| ||||| || |||||), suggesting that improvement in symptoms due to odevixibat may be delayed in some patients.
• Dose escalation: CDEC noted that patients enrolled in the PEDFIC 1 trial were assigned to receive odevixibat at a daily dose of either 40 mcg/kg or 120 mcg/kg, and patients who received odevixibat 40 mcg/kg did not have their dose escalated to 120 mcg/kg during this trial. CDEC also discussed the lack of a dose-dependent treatment response for patients because response for many end points was not greater for patients who received 120 mcg/kg per day of odevixibat compared to those who received 40 mcg/kg per day. In the CADTH pharmacoeconomic base case, patients were assumed to have their dose escalated to 120 mcg/kg per day if they had not responded after 12 weeks. Given the lack of evidence to support dose titration of odevixibat to 120 mcg/kg per day, CDEC discussed the CADTH scenario analysis in which dose escalation was removed. In this scenario, a price reduction of 97.9% would be required for odevixibat to achieve an ICER of $50,000 per QALY gained compared to standard of care alone. Given the incongruent dose response in patients assigned to 40 mcg/kg per day compared to 120 mcg/kg per day in the PEDFIC 1 trial, and the limitations noted in the extension study, evidence to justify a higher cost to the health care system for daily doses higher than 40 mcg/kg is lacking.
• Comparative evidence: There was no direct evidence comparing odevixibat to other drugs used for treating PFIC, although such drugs are not indicated for the disease and are used off-label. As such, CDEC considered evidence from a matched cohort study (OvEC) comparing clinical outcomes in patients treated with odevixibat from the PEDFIC 1 and PEDFIC 2 trials to an external control cohort of children who had not undergone SBD from a retrospective natural history study (NAPPED) submitted by the sponsor to address this gap. Although the results suggested odevixibat may confer a benefit in event-free survival, native liver survival, SBD-free survival, and overall survival, CDEC noted the results were uncertain due to methodological limitations. The inverse probability of treatment weighting (IPTW) method was used to minimize the impact of confounding on the results. However, this method does not control for the different study designs for the 2 cohorts, insufficient description of data collection methods and patient characteristics, derivation of baseline covariates and likelihood of residual confounding, and handling of missing data. These methodological limitations reduce certainty in the results and precluded CDEC from drawing conclusions from this study.
• Ethics and equity: CDEC discussed ethical and equity considerations related to odevixibat, including the significant physical, psychosocial, and financial burdens of living with and caring for someone with PFIC, especially due to cholestatic pruritus. Surgical treatment options, such as a liver transplant, are invasive and life-altering. The committee also discussed how pediatric patients with PFIC may be considered particularly vulnerable because they are living with a severe and rare disease and depend on their parents or caregivers to facilitate access to their diagnosis and support for their condition and care transitions. The committee discussed how to weigh the relatively uncertain evidence of long-term safety and efficacy of odevixibat against the harm of not recommending odevixibat for reimbursement in the context of very limited treatment options for PFIC. CDEC also noted that health equity is an important consideration when assessing this uncertainty because PFIC is a rare and severe disease and odevixibat satisfies some important unmet needs for a vulnerable population with limited treatment options.

Background

PFIC is a rare, life-shortening, heterogeneous group of liver disorders of autosomal recessive inheritance that affects the production and/or composition of bile from the liver. PFIC is characterized by an early onset of cholestasis (usually during infancy) with severe pruritus and fat malabsorption which rapidly progresses and leads to liver failure. Elevated bile acid concentrations result in ongoing liver inflammation, fibrosis, cirrhosis, and eventually liver failure. Intractable pruritus is the most troubling symptom of PFIC. PFIC is categorized into subtypes based on genetic defect, clinical presentation, laboratory findings, and liver histology. At least 6 subtypes of PFIC have been described in the literature. PFIC1 and PFIC2 represent approximately two-thirds of cases; PFIC3 represents a large portion of the remainder. PFIC is estimated to affect between 1 in every 50,000 to 100,000 children born worldwide. Although global or country-specific prevalence estimates are not available for PFIC, it is believed to be responsible for approximately 10% to 15% of cholestatic liver diseases in children and 10% to 15% of liver transplant indications in children. PFIC is a fatal disease. Survival in patients with PFIC who do not undergo SBD or liver transplant is 50% at age 10 and almost none at age 20.

The clinical experts consulted by CADTH for this review stated that although there are numerous anti-itch medications, including antihistamines and other drugs such as rifampicin that indirectly address itch, they may be effective for mild to moderate pruritus but are not effective therapies for severe pruritus. One clinical expert noted that accumulation of bile acids damages the liver; however, it is not clear whether a medication such as ursodeoxycholic acid (UDCA) is able to address this key aspect of the pathophysiology of PFIC. Surgery is also a key nonpharmacological approach, although it is not always successful, carries a high risk of morbidity, and is not suitable for a subset of patients who have cirrhosis.

Odevixibat has been approved by Health Canada for the treatment of pruritus in patients aged 6 months or older with PFIC. Odevixibat is an ileal bile acid transporter inhibitor. It is available as 200 mcg, 400 mcg, 600 mcg, and 1,200 mcg capsules. The dosage recommended in the product monograph is 40 mcg/kg administered orally once daily in the morning. If an adequate clinical response has not been achieved after 3 months of continuous therapy, the daily dose may be increased to 120 mcg/kg, with a maximum daily dose of 7,200 mcg.

Sources of Information Used by the Committee

To make its recommendation, the committee considered the following information:

• a review of a phase III, double-blind, randomized, placebo-controlled trial in children with PFIC1 and PFIC2; a nonrandomized, open-label extension study; and a matched cohort study
• patients’ perspectives gathered by 1 patient group, the Canadian Liver Foundation (CLF)
• input from public drug plans and cancer agencies that participate in the CADTH review process
• a panel of 4 clinical specialists with expertise diagnosing and treating patients with PFIC
• input from 1 clinician group, the Canadian Pediatric Hepatology Research Group (CPHRG)
• a review of the pharmacoeconomic model and report submitted by the sponsor
• a review of relevant ethical issues related to odevixibat from published literature.

Stakeholder Perspectives

Drug Program Input

Input was obtained from the drug programs that participate in the CADTH reimbursement review process. The clinical experts consulted by CADTH provided advice on the potential implementation issues raised by the drug programs.

Table 2

Responses to Questions From the Drug Programs.

Clinical Evidence

Systematic Review

Description of Studies

PEDFIC 1 (N = 62) was a phase III, multicentre (1 site in Canada), double-blind, randomized, placebo-controlled study to demonstrate the efficacy and safety of odevixibat 40 mcg/kg per day and 120 mcg/kg per day in children with PFIC1 and PFIC2. The study included up to an 8-week screening period, a 24-week treatment period, and a 4-week follow-up period. The primary outcome of the PEDFIC 1 trial was the proportion of patients who experienced at least a 70% reduction in sBA concentration from baseline to the end of treatment or reached a level of 70 μmol/L or lower after 24 weeks of treatment. This was the primary outcome used for submission to regulatory bodies outside of the US, including Canada, and therefore was considered the primary outcome of interest for the purposes of this report. Secondary outcomes included the proportion of positive pruritus assessments at the patient level over the 24-week treatment period based on the PRUCISION ObsRO instrument (note that this was the primary outcome for submission to the FDA), the change from baseline to week 24 in growth, change from baseline in sleep parameters (awakenings) measured with the PRUCISION PRO and ObsRO instruments by each 4-week interval over the 24-week treatment period, proportion of individual assessments meeting the definition of a positive pruritus assessment at the patient level from weeks 0 to 4 and weeks 0 to 12, and number of patients undergoing biliary diversion surgery or liver transplantation.

The median age of the patients in the PEDFIC 1 trial was 3.2 years and ranged from 6 months to 15.9 years. Most patients (47 of 62; 76%) were aged between 6 months and 5 years; 12 (19%) were between 6 and 12 years, and 3 (5%) were between 13 and 18 years; a limited number of patients || ||||| were older than 8 years. Median height-for-age and weight-for-age z scores were −1.70 and −0.95, respectively, indicating the patients were below their age-matched peers for growth. Most (45 patients; 73%) had PFIC2, and 17 (27%) had PFIC1. According to the investigator, almost all patients (n = 60; 97%) had a history of significant pruritus present and most (n = 42; 68%) had sBA levels of greater than 100 µmol/L (40.85 mcg/mL) within 6 months before enrolment in the study. At study entry, 50 patients (81%) were on UDCA and 41 (66%) were on rifampicin. Overall, 8 (13%) patients reported prior biliary tract surgeries (all reports of biliary diversion). Median sBA levels were elevated at baseline at 228.0 µmol/L, 188.5 µmol/L, and 254.5 µmol/L in the odevixibat 40 mcg/kg per day, odevixibat 120 mcg/kg per day, and placebo groups, respectively. Median levels of hepatic biochemical parameters were elevated at baseline, including alanine aminotransferase (ALT) (approximately 2 × upper limit of normal [ULN]), aspartate transferase (AST) (less than 2 × ULN), and total bilirubin (1.8 × ULN). Based on Child-Pugh classification, 41 patients (66%) had mild hepatic impairment and 21 (34%) had moderate hepatic impairment; no patients had severe impairment.

Efficacy Results

Mortality

Mortality was reported as a safety outcome in the PEDFIC 1 trial, and there were no deaths in the study.

Need for Surgery

The need for surgery was a secondary outcome in the PEDFIC 1 trial, and there were no surgeries for liver transplant or biliary diversion in the study.

Health-Related Quality of Life

HRQoL was assessed as an exploratory outcome using the Pediatrics Quality of Life (PEDSQL) instrument, scored on a scale of 0 to 100, with higher scores indicating improved quality of life. After 24 weeks, the least square (LS) mean difference versus placebo for the odevixibat 40 mcg/kg per day group was ||||| |||| |||||||||| |||||||| ||||| ||||||| |||||| and for the 120 mcg/kg per day group was |||| |||| ||| |||||| ||||||.

Pruritus

The sponsor designed their own instrument for assessing pruritus. The assessment of the proportion of positive pruritus responses at 24 weeks was a secondary outcome of the study. After 24 weeks of treatment with odevixibat, the between-group differences in the LS means for the comparisons of the odevixibat 40 mcg/kg per day group to placebo was 28.23% (95% CI, 9.83% to 46.64%), and the odevixibat 120 mcg/kg per day group to placebo was 21.71% (95% CI, 1.87% to 41.54%). Differences versus placebo were also observed for weeks 0 to 12 with a LS mean difference versus placebo for the odevixibat 40 mcg/kg per day group of |||||| |||| ||| ||||| ||||||| and for the 120 mcg/kg per day group of |||||| |||| ||| ||||| |||||||. At weeks 0 to 4, the differences versus placebo were smaller, particularly at the higher dose, with a LS mean difference versus placebo for the odevixibat 40 mcg/kg per day group of |||||| |||| ||| |||||| ||||||| and for the 120 mcg/kg per day group of |||||| |||| ||| |||||| |||||||.

Serum Bile Acid Levels

The primary outcome of the PEDFIC 1 trial was the proportion of patients who experienced at least a 70% reduction in fasting sBA levels from baseline to the end of treatment or reached a level of 70 μmol/L or less after 24 weeks. The adjusted difference in proportions between odevixibat 40 mcg/kg per day and placebo was ||||| |||| ||| |||||| ||||||| |||||||| ||| ||||||| |||||||||| ||| |||||||||| ||| ||||||| ||| ||||| |||| ||| |||||| ||||||| ||||||||. Between-group differences were smaller for the same outcome when assessed at 12 weeks, with an adjusted difference in proportions between odevixibat 40 mcg/kg per day and placebo was ||||| |||| ||| |||||| ||||||| and between odevixibat 120 mcg/kg per day and placebo was ||||| |||| ||| ||||||| ||||||||.

Growth

Improvement in growth (height, weight, body mass index [BMI]) was assessed as a secondary outcome by comparing changes from baseline in z scores relative to a typical pediatric growth chart. For height, the LS mean between-group difference for odevixibat versus placebo after 24 weeks was 0.32 (95% CI, 0.00 to 0.65) for the 40 mcg/kg per day group and 0.15 (95% CI, −0.18 to 0.48) for the 120 mcg/kg per day group. For weight, the LS mean between-group difference was 0.28 (95% CI, −0.01 to 0.57) for the 40 mcg/kg per day group and 0.08 (95% CI, −0.22 to 0.37) for the 120 mcg/kg per day group. For BMI, the LS mean between-group difference was |||| |||| ||| |||||| ||||| for the 40 mcg/kg per day group and ||||| |||| ||| |||||| ||||| for the 120 mcg/kg per day group.

Number of Awakenings

The changes over time in sleep parameters, specifically awakenings, was assessed as a secondary outcome using data derived from the PRUCISION pruritus instrument developed by the sponsor. The LS mean between-group difference in number of awakenings from baseline to weeks 21 to 24 was |||| |||| ||| |||||| |||||| in the 40 mcg/kg per day group and ||||| |||| ||| ||||||| ||||| in the 120 mcg/kg per day group.

Total Bilirubin

The change from baseline to week 24 in total bilirubin was an exploratory outcome. The LS mean between-group difference versus placebo in total bilirubin was |||||| |||||| |||||||| |||||| in the 40 mcg/kg per day group and ||||| |||||| |||||||| |||||| in the 120 mcg/kg per day group.

Harms Results

Adverse Events

Overall, 35 (83%) of the 42 patients who received odevixibat experienced at least 1 treatment-emergent adverse event (TEAE) as did 17 (85%) of 20 patients who received placebo; the overall incidence of TEAEs was similar in the odevixibat 40 mcg/kg per day and 120 mcg/kg per day treatment groups (83% and 84%, respectively). The most commonly reported types of events during the study were gastrointestinal disorders and infections. Overall, the most commonly reported TEAEs (≥ 10% overall) among patients who received odevixibat versus patients who received placebo were diarrhea (31% vs. |||%), pyrexia (29% vs. 25%), upper respiratory tract infection (19% vs. 15%), vomiting (17% vs. 0%), increased ALT (14% vs. 5%), and increased blood bilirubin (12% vs. 10%).

Serious Adverse Events

Treatment-emergent serious adverse events (SAEs) were reported in 3 (7%) of 42 patients who received odevixibat and in 5 (25%) of 20 patients who received placebo. No treatment-emergent SAEs were reported in the 40 mcg/kg per day treatment group. The most commonly reported types of treatment-emergent SAEs were infections, which were reported in 4 (20%) of 20 patients in the placebo group and in 1 (5%) of 19 patients in the 120 mcg/kg per day group. The only event reported in more than 1 patient overall was urinary tract infection, which was reported in 1 patient each in the placebo and 120 mcg/kg per day groups. None of the treatment-emergent SAEs led to discontinuation of treatment.

Withdrawals Due to Adverse Events

Dose interruptions due to TEAEs were reported at a higher incidence in patients who received odevixibat (9 of 42; 21%) compared with patients who received placebo (1 of 20; 5%). The highest incidence was reported among patients who received 120 mcg/kg per day (6 of 19; 32%), whereas 3 (13%) of the 23 patients in the group that received 40 mcg/kg per day had treatment interruptions due to TEAEs. In 7 of the 10 patients with treatment interruptions due to TEAEs, the events were related to elevations in hepatic biochemical test results, and treatment was interrupted as required by the protocol. All 7 cases with study drug interrupted due to hepatic biochemical test results underwent adjudication by the Data Safety Monitoring Board which assessed all events as related to the patient’s underlying disease. All these patients completed the PEDFIC 1 trial and rolled over to the PEDFIC 2 trial to receive odevixibat, except 1 patient who discontinued the study due to the inability to attend clinic visits.

One patient who received odevixibat 120 mcg/kg per day discontinued the study drug due to a TEAE of diarrhea.

Critical Appraisal

The PEDFIC 1 trial was double-blinded with steps taken to maintain blinding and allocation concealment during the randomization process. Despite randomization, there were imbalances in several baseline characteristics, suggesting that prognostic balance was not achieved, which was likely the result of the small sample size. Given the small size of the trial, there were a relatively large number of patients who discontinued treatment and who were rolled into the extension study, in which all patients were given the higher dose (120 mcg/kg) of odevixibat. Although steps were taken to account for these missing data points for outcomes such as pruritus and sBA levels, a number of key outcomes, such as PEDSQL, had data missing for more than 20% of the patient population.

With respect to external validity, major issues included that the enrolled population was limited to patients with PFIC1 and PFIC2, whereas the proposed indication does not restrict based on subtype. Additionally, the PEDFIC 1 trial assessed 2 different daily doses of odevixibat, 40 mcg/kg and 120 mcg/kg, which differs from the proposed labelling that recommends all patients begin at 40 mcg/kg per day and then titrate up to 120 mcg/kg per day if there is a lack of response at 12 weeks. The trial was not of sufficient size or duration to adequately assess key clinical outcomes such as mortality or the need for surgical intervention.

GRADE Summary of Findings and Certainty of the Evidence

The selection of outcomes for the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) assessment was based on the sponsor’s Summary of Clinical Evidence, consultation with clinical experts, and input received from patient and clinician groups and public drug plans. The following list of outcomes was finalized in consultation with expert committee members:

• Clinical outcomes:
  • mortality
  • need for surgery (biliary diversion or liver transplant)
  • growth (change from baseline to week 24 in z scores for height, weight, and BMI)
• Patient-reported outcomes:
  • PEDSQL (change from baseline to week 24 in PEDSQL Parent Report and Family Impact Module)
  • pruritus (proportion of positive pruritus assessments at the patient level at week 24, weeks 0 to 4, and weeks 0 to 12)
  • sleep parameters (change from baseline to week 21 to 24 in number of awakenings)
• Lab parameters:
  • sBA (proportion of patients with at least a 70% reduction in fasting sBA after 24 weeks or a sBA of 70 μmol/L or less at week 24 plus the same outcome for week 12)
  • liver function (change from baseline to week 24 in total bilirubin)
• Harms:
  • clinically significant diarrhea
  • adjudicated hepatic events

Table 3

Summary of Findings for Odevixibat Versus Placebo for Patients With PFIC1 and PFIC2.

Ethical Considerations

Patient group, clinician group, clinical expert, and drug program input gathered in the course of this CADTH review as well as relevant literature were reviewed to identify ethical considerations relevant to the use of odevixibat for PFIC. Ethical considerations identified in this review included those related to:

• Diagnosis, treatment, and experiences of PFIC: Ethical considerations in the context of PFIC highlighted that patients and caregivers experience a tremendous physical, psychosocial, and financial burden from unremitting pruritis (itching) that is associated with this disease. Addressing referral bias, in which referrals may be influenced by illness severity, and ensuring early diagnosis of PFIC when possible is important in preventing needless suffering and reducing the burden on the health care system. There is an unmet need for an effective disease-modifying treatment for pruritis in PFIC, given its devastating impact on patients and their families. Surgical treatment alternatives, such as a liver transplant, are invasive and life-altering.
• Clinical and economic evidence use in the evaluation of odevixibat: There are some clinically meaningful outcomes identified in the trials used to evaluate odevixibat, including a significant reduction in sBA levels and symptom relief. These studies also exhibit considerable evidentiary uncertainty. Specifically, uncertainty arises when attempting to extend efficacy results beyond the PFIC subtype 1 and 2 study population in correlating sBA to pruritis, and when considering durations exceeding the study’s 24-week time frame. Ensuring that patients are adequately informed of these evidentiary uncertainties in a shared decision-making process and that health care resources are distributed fairly and equitably are important steps in addressing these ethical concerns.
• Clinical use and implementation of odevixibat: Clinical experts indicated there was some promise in odevixibat given its potential to address some unmet needs for the treatment of PFIC-associated pruritis with a favourable safety profile. However, it is essential to emphasize the importance of equitable access regarding continuity of care and access as pediatric patients become adults.
• Health systems: The reimbursement of odevixibat brings to the forefront a complex array of ethical considerations, including those regarding opportunity costs and resource allocation in the context of uncertain evidence as well as those related to equitable access and ensuring infrastructures to support continuity of care and access.

Economic Evidence

Table 4

Cost and Cost-Effectiveness.

CDEC Information

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Indication: The treatment of pruritus in patients aged 6 months or older with progressive familial intrahepatic cholestasis

Sponsor: Medison Pharma Canada Inc.

Final recommendation: Reimburse with conditions