Drug Trials Snapshot: BYLVAY
HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the key clinical trials that supported the original FDA approval of this drug, and whether there were differences among sex, race, age, and ethnic groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.
LIMITATIONS OF THIS SNAPSHOT:
Do not rely on Snapshots to make decisions regarding medical care. Always speak to your healthcare provider about the benefits and risks of a drug.
Some of the information in this Snapshot is for presentation purposes and does not represent the approved conditions of use of this drug. Refer to the BYLVAY Prescribing Information for all of the approved conditions of use of this drug (e.g., indication(s), population(s), dosing regimen(s), safety information).
Snapshots are limited to the information available at the time of the original approval of the drug and do not provide information on who participated in clinical trials that supported later approvals for additional uses of the drug (if applicable).
BYLVAY (odevixibat)
(bil' vaye)
Albireo Pharma, Inc.
Original Approval date: July 20, 2021
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
BYLVAY is a drug used to treat pruritus (itching) due to progressive familial intrahepatic cholestasis (PFIC) in patients 3 months of age or older.
PFIC is a rare condition where bile acid, which is produced in the liver to help digest dietary fats and oils, is unable to be secreted out of liver leading to liver injury (cholestatic liver injury).
How is this drug used?
BYLVAY is available as a pellet or capsule. Based on the patient’s weight, the healthcare provider will recommend a certain dose to be taken by mouth once a day in the morning with food.
Who participated in the clinical trials?
The FDA approved BYLVAY based on evidence of efficacy from a clinical trial (Trial 1/NCT03566238) of 62 patients with PFIC type 1 or type 2 and at least medium pruritus. The trial was conducted at 28 sites in 12 countries in Australia, Canada, France, Germany, Great Britain, Israel, Italy, Netherlands, Poland, Saudi Arabia, Turkey, and the United States.
What are the benefits of this drug?
In the trial, BYLVAY-treated patients demonstrated an improvement in pruritus (itching) compared to those who were treated with placebo.
What are the benefits of this drug (results of trials used to assess efficacy)?
Patients were randomized to placebo (n=20), BYLVAY 40 µg/kg (n=23), or BYLVAY 120 µg/kg (n=19). Given the patients’ young age, caregivers assessed patients’ scratching twice daily (once in the morning and once in the evening) on a scale ranging from 0 (no scratching) to 4 (worst possible scratching).
For each patient, the percentage of assessments over the 24-week treatment period that were scored as 0 (no scratching) or 1 (a little scratching) was calculated. Table 1 displays the mean of this outcome for each treatment group.
Table 1. Mean1 Percentage of Assessments Over the Treatment Period Scored as 0 (No Scratching) or 1 (A Little Scratching) (%)
|
Parameter |
Placebo |
BYLVAY |
|
|---|---|---|---|
|
40 µg/kg/day |
120 µg/kg/day |
||
|
Mean (SE) |
13.2 (8.7) |
35.4 (8.1) |
30.1 (9.0) |
|
Mean difference vs. placebo (95% CI) |
|
22.2 (4.7, 39.6) |
16.9 (-2.0, 35.7) |
Source: Adapted from FDA Review
1 Based on least squares means from analysis of covariance model with daytime and nighttime baseline pruritus scores as covariates and treatment group and stratification factors (i.e., PFIC type and age category) as fixed effects.
Figure 1. Mean* of the Worst Weekly Average Scratching Scores for Each Month
Source: Adapted from FDA Review
*Figure 1 presents least squares means
Based on a mixed model repeated measure (MMRM) analysis accounting for baseline score, treatment group, time (in months), treatment-by-baseline interaction, treatment-by-time interaction, and stratification factors (i.e., PFIC type and age category). Missing data were accounted for using placebo reference multiple imputation.
Were there any differences in how well the drug worked in clinical trials among sex, race and age?
The observed effect of BYLVAY was slightly larger for females than males. Because of limited data, this difference may be due to chance.
- Sex: BYLVAY appears to work similarly in males and females.
- Race: The number of patients of races other than White was small; therefore, differences in how BYLVAY worked among races could not be determined.
- Age: BYLVAY appears to work similarly in patients 6 months to 5 years old and in patients 6 years to 12 years old. There were only 3 patients aged 13 years to 18 years old.
Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?
Table 2. Mean1 Percentage of Assessments Over the Treatment Period Scored as 0 (No Scratching) or 1 (A Little Scratching) (%) by Sex and Age.
|
Parameter |
Placebo |
BYLVAY 40 or 120 µg/kg/day |
|---|---|---|
|
Male |
N=12 |
N=19 |
|
Mean (SE) |
10.9 (4.5) |
28.1 (7.8) |
|
Female |
N=8 |
N=23 |
|
Mean (SE) |
6.0 (3.8) |
32.1 (6.9) |
|
6 months to 5 years |
N=16 |
N=31 |
|
Mean (SE) |
7.4 (3.4) |
28.8 (6.1) |
|
6 to 12 years |
N=3 |
N=9 |
|
Mean (SE) |
9.8 (7.0) |
38.7 (12.7) |
Source: Adapted from FDA Review
Unadjusted means There were only 3 patients 13 to 18 years old
What are the possible side effects?
The most common side effects include liver test abnormalities (liver enzymes and bilirubin were elevated), diarrhea (that required stopping BYLVAY), abdominal pain, vomiting, and new onset or worsening of fat-soluble vitamin deficiency.
Warning and Precautions include monitoring for liver test abnormalities, diarrhea, fat-soluble vitamin deficiency, and to interrupt or discontinue the drug in the event the adverse reaction persistent or recurs.
What are the possible side effects (results of trials used to assess safety)?
Table 3 summarizes the frequency of clinical adverse events (AEs), regardless of causality, reported in ≥2% and at a rate greater than placebo in patients treated with BYLVAY in Trial 1.
Table 3. Clinical Adverse Reactions in Trial 1
|
Preferred Term |
Placebo |
BYLVAY |
BYLVAY |
BYLVAY |
|---|---|---|---|---|
|
Diarrhea |
2 (10.0) |
9 (39.1) |
4 (21.1) |
13 (31.0) |
|
Transaminases increased (ALT, AST) |
1 (5.0) |
3 (13.0) |
4 (21.1) |
7 (16.7) |
|
Vomiting |
0 |
4 (17.4) |
3 (15.8) |
7 (16.7) |
|
Abdominal pain |
0 |
3 (13.0) |
3 (15.8) |
6 (14.3) |
|
Blood bilirubin increased |
2 (10.0) |
3 (13.0) |
2 (10.5) |
5 (11.9) |
|
Fat-soluble vitamin deficiency (A, D, E) |
1 (5.0) |
0 |
3 (15.8) |
3 (7.1) |
|
Splenomegaly |
0 |
0 |
2 (10.5) |
2 (4.8) |
|
Cholelithiasis |
0 |
0 |
1 (5.3) |
1 (2.4) |
|
Dehydration |
0 |
0 |
1 (5.3) |
1 (2.4) |
|
Fracture |
0 |
1 (4.3) |
0 |
1 (2.4) |
Source: Adapted from FDA Review
Abbreviations: ALT, alanine transaminase; AST, aspartate transferase
Were there any differences in side effects of the clinical trials among sex, race, and age?
The trial was too small to determine if there were any differences in sex, race, and age subgroups.
Table 4. Overview of Side Effects by Sex, Race, and Age in Pediatric Patients, Trial 1, Safety Population
|
Demographic Variable |
BYLVAY 40 or 120 µg/kg/day |
Placebo |
||
|---|---|---|---|---|
|
All Grades |
Grade 3 |
All Grades |
Grade 3 |
|
|
Sex, n (%) |
||||
|
Female |
18/23 (78.3) |
1/23 (4.3) |
8/8 (100) |
0/8 (0) |
|
Male |
17/19 (89.5) |
2/19 (10.5) |
9/12 (75.0) |
2/12 (16.7) |
|
Race, n (%) |
||||
|
Asian |
0/1 (0) |
0/1 (0) |
1/1 (100) |
0/1 (0) |
|
Black or African American |
2/2 (100) |
0/2 (0) |
0/0 (NA) |
0/0 (NA) |
|
White |
29/35 (82.9) |
3/35 (8.6) |
14/17 (82.4) |
2/17 (11.8) |
|
Other |
4/4 (100) |
0/4 (0) |
2/2 (100) |
0/2 (0) |
|
Age group, n (%) |
||||
|
6 months to 5 years |
27/31 (87.1) |
2/31 (6.5) |
13/16 (81.2) |
2/16 (12.5) |
|
6 to 12 years |
7/9 (77.8) |
1/9 (11.1) |
3/3 (100) |
0/3 (0) |
|
13 to 18 years |
1/2 (50.0) |
0/2 (0) |
1/1 (100) |
0/1 (0) |
Source: FDA reviewer’s analysis
Abbreviation: N, number of patients in the safety population; n, number of patients with given characteristic; Ns, total number of patients in each category; NA, not applicable
DEMOGRAPHICS SNAPSHOT
Figure 2 summarizes how many males and females were enrolled in the clinical trial used to evaluate the safety and efficacy of BYLVAY.
Figure 2. Baseline Demographics by Sex (Efficacy Population)
Source: Adapted from FDA Review
Figure 3 summarizes the percentage of patients by race enrolled in the clinical trial used to evaluate the efficacy of BYLVAY.
Figure 3. Baseline Demographics by Race1 (Efficacy Population)
Source: Adapted from FDA Review
1 The trial population from Middle Eastern countries was included under race category “White” by the Applicant.
Figure 4 summarizes the percentage of patients by age enrolled in the clinical trial used to evaluate the efficacy of BYLVAY.
Figure 4. Baseline Demographics by Age (Efficacy Population)
Source: Adapted from FDA Review
Only one adequate and well-controlled trial was conducted.
Who participated in the trials?
Table 4. Baseline Demographics of Enrolled Patients in the Clinical Trial (Efficacy Population)
|
Demographic Parameters |
Trial 1 |
|---|---|
|
Sex, n (%) |
|
|
Male |
31 (50%) |
|
Female |
31 (50%) |
|
Race, n (%) |
|
|
White1 |
52 (84%) |
|
Asian |
2 (3%) |
|
Black or African American |
2 (3%) |
|
Other |
6 (10%) |
|
Age |
|
|
Mean years (SD) |
4.2 (3.9) |
|
Median (years) |
3.2 |
|
Min, max (years) |
0.5, 15.9 |
|
Age group, n (%) |
|
|
Less than 5 years |
47 (76%) |
|
6 years to 12 years |
12 (19%) |
|
13 years to 18 years |
3 (5%) |
Source: Adapted from FDA Review
1 The trial population from Middle Eastern countries was included under race category “White” by the Applicant.
How were the trials designed?
There was one trial that evaluated the efficacy of BYLVAY in 62 PFIC patients with at least moderate pruritus (itching). Patients received BYLVAY or placebo once daily for 24 weeks. Given the patients’ young age, caregivers assessed patients’ scratching twice daily (once in the morning and once in the evening) on a scale ranging from 0 (no scratching) to 4 (worst possible scratching).
How were the trials designed?
The efficacy of BYLVAY was assessed in a 24-week, randomized, double-blind, placebo-controlled clinical trial. Given the patients’ young age, caregivers assessed patients’ scratching twice daily (once in the morning and once in the evening) on a scale ranging from 0 (no scratching) to 4 (worst possible scratching).
For each patient, the percentage of assessments over the 24-week treatment period that were scored as 0 (no scratching) or 1 (a little scratching) was calculated, and the mean of this outcome for the treatment groups was compared to mean in the placebo group.
GLOSSARY
CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.
COMPARATOR: A previously available treatment or placebo that is compared to the actual drug being tested.
EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.
PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.
SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.