Drug Trials Snapshots: IQIRVO
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 IQIRVO Prescribing Information for all 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).
IQIRVO (elafibranor)
eye-ker-vo
IPSEN BIOPHARM LTD
Original Approval date: June 10, 2024
DRUG TRIALS SNAPSHOT SUMMARY
What is the drug for?
IQIRVO is a peroxisome proliferator-activated receptor (PPAR) agonist indicated for the treatment of primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA) in adults who have an inadequate response to UDCA or as monotherapy in patients unable to tolerate UDCA.
IQIRVO is not recommended for patients who have or develop decompensated cirrhosis (e.g., ascites, variceal bleeding, hepatic encephalopathy).
How is this drug used?
IQIRVO is a tablet that is taken once daily.
Who participated in the clinical trials?
The FDA approved IQIRVO based on evidence from a clinical trial of 161 patients with PBC with inadequate response or intolerance to UDCA. The trial was conducted at 82 sites in 14 countries, including two countries in North America, three countries in Latin America, eight countries in Europe, and one country in Africa.
Approximately 43% (69) of the patients were from North America, including patients from the United States and Canada; 35% (56) from Europe; 16% (26) from Latin America; and 6% (10) from the rest of the world.
The same trial was used to assess efficacy and safety.
How were the trials designed?
IQIRVO was evaluated in Study 1 (NCT04526665), a randomized, double-blind, placebo-controlled clinical trial of 161 patients with PBC with inadequate response or intolerance to UDCA. Patients received IQIRVO 80 mg once daily or placebo for at least 52 weeks and up to 104 weeks. The benefit of IQIRVO was evaluated based on the percentage of patients who achieved biochemical response at Week 52, where biochemical response measured liver enzymes (alkaline phosphatase [ALP] and total bilirubin [TB]) that are found in the blood or serum.
How were the trials designed?
The safety and efficacy of IQIRVO were established in one randomized, double-blind, placebo-controlled clinical study (Study 1) evaluating patients with PBC with inadequate response or intolerance to UDCA. Patients were included in the study if their ALP was ≥1.67x the upper limit of normal (ULN) and TB was ≤2x ULN. Patients were excluded if they had other liver disease or in case of decompensated cirrhosis. Patients were randomized in a 2:1 ratio to receive either IQIRVO 80 mg once daily (N=108) or placebo (N=53) and continued on treatment for the entire duration of the study. Patients were treated for at least 52 weeks and up to 104 weeks. The primary endpoint was the proportion of patients achieving biochemical response at Week 52, where biochemical response measured liver enzymes that are found in the blood.
DEMOGRAPHICS SNAPSHOT
Figure 1 summarizes the percentage of male and female patients enrolled in the clinical trial that evaluated the efficacy of IQIRVO.
Figure 1. Baseline Demographics by Sex Efficacy Population
Source: Adapted from FDA Review
Figure 2 summarizes the percentage of patients by race enrolled in the clinical trial that evaluated the efficacy of IQIRVO.
Figure 2. Baseline Demographics by Race Efficacy Population
Source: Adapted from FDA Review
Figure 3 summarizes the percentage of patients by age enrolled in the clinical trial that evaluated the efficacy of IQIRVO. Notably, the disease affects predominantly females (approximately 90%) in their 50s and 60s.
Figure 3. Baseline Demographics by Age Efficacy Population
Source: Adapted from FDA Review
Data on participants’ ethnicity was not collected in Study 1.
Who participated in the trials?
Table 1. Baseline Demographics Efficacy Population
| Characteristic | IQIRVO N=108 |
Placebo N=53 |
Total N=161 |
| Sex n (%) | |||
| Male | 6 (5.6) | 1 (1.9) | 7 (4.3) |
| Female | 102 (94.4) | 52 (98.1) | 154 (95.7) |
| Age group years n (%) | |||
| <65 | 83 (76.9) | 43 (81.1) | 126 (78.3) |
| ≥65 | 25 (23.1) | 10 (18.9) | 35 (21.7) |
| Age years | |||
| Mean (SD) | 57.5 (8.4) | 56.4 (9.3) | 57.1 (8.7) |
| Median (min max) | 58.0 (38, 75) | 56.0 (36, 76) | 57.0 (36, 76) |
| Race n (%) | |||
| White | 101 (93.5) | 46 (86.8) | 147 (91.3) |
| Black or African American | 2 (1.9) | 0 (0.0) | 2 (1.2) |
| Asian | 1 (0.9) | 3 (5.7) | 4 (2.5) |
| American Indian or Alaska Native | 0 (0.0) | 1 (1.9) | 1 (0.6) |
| Other | 3 (2.8) | 2 (3.8) | 5 (3.1) |
| Not reported | 1 (0.9) | 1 (1.9) | 2 (1.2) |
Source: Adapted from FDA Review
Abbreviations: SD, standard deviation
What are the benefits of this drug?
More patients achieved biochemical response after 52 weeks of treatment with IQIRVO in comparison to those who were treated with placebo. Biochemical response is a lowering of the level of a liver enzyme (ALP) that is found in the blood and that is elevated in patients with PBC.
IQIRVO was approved under FDA’s accelerated approval program, which provides earlier patient access to a promising new drug while the company continues to conduct clinical trials to confirm that the drug works well.
What are the benefits of this drug (results of trials used to assess efficacy)?
The primary efficacy endpoint was the proportion of patients achieving biochemical response at Week 52, with biochemical response defined as ALP <1.67x ULN and TB ≤ULN and ALP decrease greater or equal to 15%.
Table 2 presents results at Week 52 for the percentage of patients who achieved biochemical response, achieved each component of biochemical response, and achieved ALP normalization. IQIRVO demonstrated greater improvement on biochemical response and ALP normalization at Week 52 compared to placebo. Overall, 96% of patients had a baseline TB concentration less than or equal to ULN. Therefore, improvement in ALP was the main contributor to the biochemical response rate results at Week 52.
Table 2. Efficacy Results at Week 52 Efficacy Population
| Parameter | IQIRVO N=108 n (%) |
Placebo N=53 n (%) |
Treatment Difference % (95% CI) |
| Biochemical response ratea | 55 (51) | 2 (4) | 47 (32 57) |
| Components of biochemical response | |||
| ALP <1.67x ULN | 56 (52) | 5 (9) | 42 (27, 53) |
| Decrease in ALP of at least 15% | 81 (75) | 9 (17) | 58 (43, 69) |
| TB ≤ULN | 92 (85) | 44 (83) | 2 (-9, 16) |
| ALP normalizationb | 16 (15) | 0 (0) | 15 (6, 23) |
Source: Adapted from FDA Review
aBiochemical response is defined as ALP <1.67-times ULN and TB ≤ULN and ALP decrease from baseline ≥15% at Week 52. The p-value from the exact Cochran–Mantel–Haenszel (CMH) test was <0.0001.
bNormalization of ALP at Week 52 is defined as ALP ≤ULN. The p-value from the exact CMH test was 0.0019.
Abbreviations: ALP alkaline phosphatase; CI confidence interval; N number of patients in treatment group; n number of events; TB total bilirubin; ULN upper limit of normal
Were there any differences in how well the drug worked in clinical trials among sex, race, and age?
- Sex: Because almost all participants were female, differences between sexes in how IQIRVO worked could not be determined.
- Race: The number of patients of races other than White was small; therefore, differences in how IQIRVO worked among races could not be determined.
- Age: IQIRVO worked similarly in patients younger and older than 65 years of age.
Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?
Subgroup analyses were conducted to assess the potential for differences in the treatment effect of patients who achieved biochemical response at Week 52 for various demographic groups in Study 1. The results of subgroup analyses are shown in Table 3. The treatment effect of IQIRVO compared to placebo appeared consistent across age groups. However, there was an insufficient number of male patients and patients of races other than White to determine whether IQIRVO worked differently in different sex and races.
Table 3. Efficacy Results by Subgroup Efficacy Population
| Subgroup | IQIRVO N=108 n/Ns (%) |
Placebo N=53 n/Ns (%) |
Treatment Difference % (95% CI) |
| Sex | |||
| Male | 3/6 (50.0) | 0/1 (0) | 50.0 (-35.3, 81.2) |
| Female | 52/102 (51.0) | 2/52 (3.8) | 47.7 (32.2, 57.6) |
| Race | |||
| White | 50/101 (49.5) | 2/46 (4.3) | 46.3 (29.8, 56.4) |
| Othera | 5/7 (71.4) | 0/7 (0) | 71.4 (21.2, 91.8) |
| Age | |||
| <65 | 43/83 (51.8) | 2/43 (4.7) | 47.2 (29.6, 58.2) |
| ≥65 | 12/25 (48.0) | 0/10 (0) | 48.0 (14.9, 66.5) |
Source: Adapted from FDA review
aOther includes: Black or African American (n=2), Asian (n=4), American Indian or Alaska Native (n=1), not reported (n=2), and other (n=5)
Abbreviations: CI confidence interval; N number of patients in the subgroup; n number of events; Ns total number of patients for each specific subgroup and were assigned to that specific arm
What are the possible side effects?
The most common side effects that occurred ≥5% in IQIRVO-treated patients as compared to placebo were weight gain, diarrhea, abdominal pain, nausea, vomiting, arthralgia, constipation, muscle injury, fracture, gastroesophageal reflux disease, dry mouth, weight loss, and rash.
The label includes warnings for muscle pain, muscle weakness, severe muscle injury requiring hospitalization, fractures, drug-induced liver injury, hypersensitivity reactions, and biliary obstruction. In addition, in animal studies, harm to fetal and newborn development occurred.
What are the possible side effects (results of trials used to assess safety)?
Table 4. Common Adverse Reactions Occurring During the Double-Blind Period in Adult Patients With PBC (Study 1)a Safety Population
| Adverse Reactionb | IQIRVO N=108 n (%) |
Placebo N=53 n (%) |
| Weight gainc | 25 (23) | 11 (21) |
| Diarrhea | 12 (11) | 5 (9) |
| Abdominal painc | 12 (11) | 3 (6) |
| Nausea | 12 (11) | 3 (6) |
| Vomiting | 12 (11) | 1 (2) |
| Arthralgia | 9 (8) | 2 (4) |
| Constipation | 9 (8) | 1 (2) |
| Muscle painc | 8 (7) | 1 (2) |
| Fracturec | 7 (6) | 0 |
| Gastroesophageal reflux disease | 7 (6) | 1 (2) |
| Dry mouth | 5 (5) | 1 (2) |
| Weight loss | 5 (5) | 0 |
| Rashc | 5 (5) | 2 (4) |
Source: Adapted from IQIRVO Prescribing Information
aIncluded 8 patients (5%) who were intolerant to UDCA and initiated treatment as monotherapy: 6 patients (5%) in the IQIRVO arm and 2 patients (4%) in the placebo arm.
bOccurring in greater than or equal to 5% of patients in the IQIRVO treatment arm and at an incidence greater than or equal to 1% higher than in the placebo treatment arm.
cWeight gain, abdominal pain, muscle pain, fracture, and rash include other related terms.
Were there any differences in side effects among sex, race, and age?
- Sex: The number of males was small; therefore, differences in side effects of IQIRVO among sex subgroups could not be determined.
- Race: The number of patients of races other than White was small; therefore, differences in side effects of IQIRVO among races could not be determined.
- Age: The number of patients 65 years of age and older was limited; therefore, differences in side effects in patients younger than 65 years of age versus patients in other age groups could not be determined.
Were there any differences in side effects of the clinical trials among sex, race, and age groups?
Table 5 shows the side effects by sex, race, and age.
Table 5. Side Effects by Sex, Race, and Age Safety Population
| Characteristic | IQIRVO N=108 n/Ns (%) |
Placebo N=53 n/Ns (%) |
Risk Difference % (95% CI) |
| Sex | |||
| Female | 98/102 (96.1) | 47/52 (90.4) | 5.7 (-2.1, 17.1) |
| Male | 6/6 (100) | 1/1 (100) | 0.0 (-42.8, 81.8) |
| Age group years | |||
| <65 | 80/83 (96.4) | 39/43 (90.7) | 5.7 (-2.8, 18.4) |
| ≥65 | 24/25 (96.0) | 9/10 (90.0) | 6.0 (-12.1, 37.5) |
| Age group ≥75 years | |||
| ≥75 | 1/1 (100) | 3/3 (100) | 0.0 (-83.7, 63.1) |
| Race | |||
| American Indian or Alaska Native | 0/0 (NA) | 1/1 (100) | NA |
| Asian | 1/1 (100) | 3/3 (100) | 0.0 (-83.7, 63.1) |
| Black or African American | 2/2 (100) | 0/0 (NA) | NA |
| White | 97/101 (96.0) | 41/46 (89.1) | 6.9 (-1.4, 19.5) |
| Not reported | 1/1 (100) | 1/1 (100) | 0.0 (-88.5, 88.5) |
| Other | 3/3 (100) | 2/2 (100) | 0.0 (-61.5, 70.6) |
Source: Adapted from FDA Review
Abbreviations: CI confidence interval; N number of patients in treatment arm; n number of patients with adverse event; NA not applicable; Ns total number of patients for each specific subgroup and were assigned to that specific arm
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 used in clinical trials 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.