Drug Trials Snapshots: VOYDEYA
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 VOYDEYA 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).
VOYDEYA (danicopan)
(voi-day-uh)
Alexion Pharmaceuticals
Approval date: March 29, 2024
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
VOYDEYA is a prescription drug that is a complement factor D inhibitor, indicated as an add-on therapy to ravulizumab or eculizumab for the treatment of extravascular hemolysis (EVH) in adults with paroxysmal nocturnal hemoglobinuria (PNH)
How is this drug used?
VOYDEYA is an oral capsule that is taken three times daily.
Who participated in the clinical trials?
The FDA approved VOYDEYA based on evidence from one main clinical trial, ALXN2040-PNH-301, in 84 subjects with PNH and clinically significant EVH. Efficacy was based on a prespecified interim analysis when approximately 75% of the planned 84 subjects (63 subjects) reached the end of Treatment Period 1 (VOYDEYA [n=42] or placebo [n=21]). The trial was conducted in 15 countries including Spain, France, Italy, Poland, Japan, Brazil, Canada, Korea, Malaysia, Thailand, Czechia, Greece, Israel, United Kingdom, and the United States.
There were 9 subjects included in the ALXN2040-PNH-301 trial from the United States and 54 subjects were included from sites outside of the United States. The same trial was used to assess efficacy and safety.
How were the trials designed?
VOYDEYA was evaluated in one main clinical trial of subjects with PNH and clinically significant EVH. Study ALXN2040-PNH-301 was a multi-center, randomized, double-blind, placebo-controlled 24-week trial in adults with PNH with clinically significant EVH on treatment with a stable regimen of an anti-C5 treatment (either eculizumab or ravulizumab) for at least six months prior. The patients were randomized to VOYDEYA or placebo for 12 weeks in addition to background ravulizumab or eculizumab treatment. After Week 12, all patients received VOYDEYA in combination with their background ravulizumab or eculizumab treatment up to Week 24.
How were the trials designed?
The safety and efficacy of VOYDEYA was established in one main clinical trial, ALXN2040-PNH-301, based on the interim analysis of the planned 84 subjects (63 subjects) enrolled with PNH with clinically significant EVH.
ALXN2040-PNH-301 was a multiple-region, randomized, double-blind, placebo-controlled study in patients with PNH with clinically significant EVH defined by defined by anemia (hemoglobin [Hgb] ≤9.5 g/dL) with absolute reticulocyte count ≥120 × 109/L with or without transfusion support. The study enrolled patients with PNH who had been treated with a stable dose of ravulizumab or eculizumab for at least the previous six months.
Patients were randomized to VOYDEYA or placebo in a 2:1 ratio for 12 weeks in addition to background ravulizumab or eculizumab treatment. After Week 12, all patients received VOYDEYA in combination with their background ravulizumab or eculizumab treatment up to Week 24. After Week 24, patients could enter a long-term extension period and continue to receive VOYDEYA with background ravulizumab or eculizumab. Efficacy was based on a primary endpoint of the change in Hgb level from Baseline to Week 12. Other efficacy measures included the proportion of patients with Hgb increase of ≥2 g/dL at Week 12 in the absence of transfusions, the proportion of patients with transfusion avoidance through Week 12, the change from Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scores at Week 12, and change from Baseline in absolute reticulocyte count at Week 12.
DEMOGRAPHICS SNAPSHOT
Figure 1 summarizes how many male and female patients were enrolled in the clinical trial used to evaluate the efficacy of VOYDEYA.
Figure 1. Baseline Demographics by Sex, Safety Population
Source: Adapted from FDA review
Figure 2 summarizes how many patients by race were enrolled in the clinical trial used to evaluate the efficacy of VOYDEYA.
Figure 2. Baseline Demographics by Race, Safety Population
Source: Adapted from FDA review
Figure 3 summarizes how many patients by age were enrolled in the clinical trial used to evaluate the efficacy of VOYDEYA.
Figure 3. Baseline Demographics by Age, Safety Population
Source: Adapted from FDA review
Figure 4 summarizes how many patients by ethnicity were enrolled in the clinical trial used to evaluate the efficacy of VOYDEYA.
Figure 4. Baseline Demographics by Ethnicity, Safety Population
Source: Adapted from FDA review
Who participated in the trials?
Table 1. Baseline Demographics, Efficacy Population
| Parameter | VOYDEYA N=42 |
Placebo N=21 |
|---|---|---|
| Age, years | ||
| Mean (SD) | 55 (16) | 53 (14) |
| Median | 58 | 53 |
| Min, max | 25, 80 | 29, 75 |
| Age group, n (%) | ||
| <65 | 30 (71.4) | 17 (81.0) |
| ≥65 | 12 (28.6) | 4 (19.0) |
| Sex, n (%) | ||
| Male | 19 (45.2) | 7 (33.3) |
| Female | 23 (54.8) | 14 (66.7) |
| Race, n (%) | ||
| American Indian or Alaska Native | 1 (2.4) | 0 |
| Asian | 18 (42.9) | 7 (33.3) |
| Black or African American | 1 (2.4) | 0 |
| White | 19 (45.2) | 9 (42.9) |
| Other | 1 (2.4) | 0 |
| Unknown | 0 | 1 (4.8) |
| Not reported | 2 (4.8) | 4 (19.0) |
| Ethnicity, n (%) | ||
| Hispanic or Latino | 4 (9.5) | 0 |
| Not Hispanic or Latino | 34 (81.0) | 17 (81.0) |
| Not reported | 4 (9.5) | 4 (19.0) |
Source: Adapted from VOYDEYA Prescribing Information
Abbreviations: SD, standard deviation
What are the benefits of this drug?
One trial in adults with PNH and EVH despite previous treatment with a stable regimen of anti C5 treatment (either eculizumab or ravulizumab) for at least six months, demonstrated superiority of VOYDEYA in combination with ravulizumab or eculizumab compared to placebo in combination with ravulizumab or eculizumab in all efficacy measures with statistically significant results.
What are the benefits of this drug (results of trials used to assess efficacy)?
Evidence of benefit is primarily derived from ALXN2040-PNH-301, a randomized, double-blind, placebo-controlled study in adults with PNH with clinically significant EVH, defined by anemia (Hgb ≤9.5 g/dL) and absolute reticulocyte count ≥120 x 109/L with or without transfusion support, despite treatment with a stable dose of anti-C5 treatment (ravulizumab or eculizumab) for at least the previous six months. Eighty-six subjects were randomized 2:1 to receive VOYDEYA or placebo three times daily in combination with anti-C5 therapy throughout the duration of the 12-week randomized controlled period (Treatment Period 1). Efficacy was based on a prespecified interim analysis when approximately 75% of the planned 84 subjects (63 subjects) reached the end of Treatment Period 1 (VOYDEYA [n=42] or placebo [n=21]). After 12 weeks of therapy, VOYDEYA was superior to placebo on: (1) Increasing hemoglobin from baseline (the mean change in hemoglobin from baseline in the VOYDEYA arm was 2.9 g/dL compared to 0.5 g/dL in the placebo arm (p=0.0007); (2) Increase in hemoglobin equal to 2 g/dL in the absence of transfusion (60% of VOYDEYA treated patients had a Hgb increase of 2 g/dL without transfusion compared to no patients in the control arm [p<0.0001]); (3) Transfusion avoidance, defined as remaining transfusion free and not requiring a transfusion, as per protocol-specified guidelines through Week 12, which occurred in 83% of patients who received VOYDEYA compared with 38% in the placebo arm (p=0.0004); (4) The mean improvement from baseline in the FACIT-Fatigue score (a measure of fatigue-related symptoms and impacts) was 8.0 in the VOYDEYA arm compared to 1.9 in the placebo group (p=0.0021); and (5) Decreasing absolute reticulocyte count (the mean change from baseline in absolute reticulocyte count was 83.8 × 109/L in the VOYDEYA arm and 3.5 × 109/L in the placebo arm [p<0.0001]), which reflects a reduced need to produce new red blood cells.
Table 2. Efficacy Results, Efficacy Population
| Parameter | VOYDEYA N=42 |
Placebo N=21 |
|---|---|---|
| Change in Hgb levela | ||
| Mean change from Baseline to Week 12 (g/dL) | 2.9 | 0.5 |
| Treatment difference (95% CI) | 2.4 (1.7, 3.2) | |
| p-value | 0.0007b | |
| Proportion of patients with Hgb increase of ≥2 g/dL in the absence of transfusionc | ||
| At Week 12 (%) | 59.5 | 0 |
| Treatment difference (95% CI) | 46.9 (29.2, 64.7) | |
| p-value | <0.0001 | |
| Proportion of patients with transfusion avoidancec | ||
| Through 12-Week treatment period (%) | 83.3 | 38.1 |
| Treatment difference (95% CI) | 41.7 (22.7, 60.8) | |
| p-value | 0.0004 | |
| Change in FACIT-Fatigue scored | ||
| Mean change from Baseline to Week 12 | 8.0 | 1.9 |
| Treatment difference (95% CI) | 6.1 (2.3, 9.9) | |
| p-value | 0.002e | |
| Change in absolute reticulocyte countd | ||
| Mean change from Baseline to Week 12 (109/L) | -84 | 4 |
| Treatment difference (95% CI) | -87 (-118, -57) | |
| p-value | <0.0001e | |
Source: Adapted from VOYDEYA Prescribing Information
a The model included the fixed, categorical effects of treatment group, study visit, and study visit-by-treatment group interaction, as well as the fixed, continuous covariate of baseline value and the randomization stratification factor of transfusion history. An unstructured covariance matrix was used to model the within-patient errors.
b Statistical significance of the treatment group difference was evaluated via a re-randomization test method. The p-value for the re-randomization test was calculated as the number of re-randomized treatment group differences that were more extreme than the treatment group difference calculated under the actual randomization divided by the total number of simulated re-randomizations.
c The proportions were compared between treatment groups using the Cochrane-Mantel-Haenszel (CMH) test stratified by randomization stratification factors of transfusion history and screening Hgb level. The p-value was from the stratified CMH test.
d The model included the fixed, categorical effects of treatment group, study visit, and study visit-by-treatment group interaction, as well as the fixed, continuous covariate of baseline value and the randomization stratification factors of transfusion history and screening Hgb level. An unstructured covariance matrix was used to model the within-patient errors. Fatigue-related symptoms and impacts were assessed using a patient reported outcome instrument, FACIT-Fatigue (score range from 0 to 52 with higher scores indicating less fatigue).
e The p-value was for the difference of LS mean from the mixed models for repeated measures.
Abbreviations: CI, confidence interval; FACIT, Functional Assessment of Chronic Illness Therapy; Hgb, hemoglobin; LS, least-squares
Were there any differences in how well the drug worked in clinical trials among sex, race, and age?
- Sex: VOYDEYA worked similarly in males and females.
- Race: The number of patients of races other than White was small; therefore, differences in how VOYDEYA worked among races could not be determined.
- Age: VOYDEYA worked similarly in patients younger and older than 45 years of age.
Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?
The subgroup analysis by sex and age were generally similar for the efficacy of VOYDEYA. The number of Asian and Black or African American subjects were small and therefore the differences in how VOYDEYA worked among races could not be compared. The number of Hispanic or Latino subjects was also small and therefore the differences in how VOYDEYA worked among ethnicities could not be compared.
Table 3 summarizes efficacy results by sex, race, age, and ethnicity based on primary endpoint in Trial ALXN2040-PNH-301.
Table 3. Change from Baseline in Hemoglobin (g/dL) by Subgroups During the 12-Week Treatment Period 1, Efficacy Population
| Subgroup | VOYDEYA | Placebo | Difference (95% CI) |
||
|---|---|---|---|---|---|
| N | LSM (95% CI) | N | LSM (95% CI) | ||
| Overall | 42 | 2.94 (2.52, 3.36) | 21 | 0.50 (-0.13, 1.12) | 2.44 (1.69, 3.20) |
| Sex | |||||
| Male | 19 | 2.94 (2.21, 3.67) | 7 | 0.74 (-0.46, 1.94) | 2.20 (0.81, 3.60) |
| Female | 23 | 2.96 (2.33, 3.58) | 14 | 0.30 (-0.54, 1.14) | 2.65 (1.61, 3.70) |
| Race | |||||
| American Indian or Alaska Native | 1 | NA | 0 | NA | NA |
| Asian | 18 | 3.48 (2.86, 4.09) | 7 | 0.64 (-0.42, 1.69) | 2.84 (1.65, 4.03) |
| Black or African American | 1 | NA | 0 | NA | NA |
| White | 19 | 2.78 (2.11, 3.45) | 9 | -0.18 (-1.17, 0.81) | 2.96 (1.77, 4.15) |
| Other or Not reported or Unknown | 3 | 2.08 (0.48, 3.68) | 5 | 1.00 (-0.53, 2.54) | 1.08 (-1.05, 3.21) |
| Region | |||||
| North America | 8 | NA | 0 | NA | NA |
| Non-North America | 34 | 2.97 (2.55, 3.40) | 21 | 0.45 (-0.13, 1.02) | 2.52 (1.82, 3.23) |
| Age group, years | |||||
| <65 | 30 | 2.88 (2.37, 3.39) | 17 | 0.58 (-0.14, 1.31) | 2.30 (1.42, 3.18) |
| ≥65 | 12 | 3.27 (2.44, 4.10) | 4 | 0.43 (-1.00, 1.87) | 2.84 (1.17, 4.51) |
| From Japan | |||||
| Yes | 5 | NA | 2 | NA | NA |
| No | 37 | 3.00 (2.53, 3.47) | 19 | 0.62 (-0.06, 1.31) | 2.38 (1.55, 3.20) |
Source: Adapted from FDA review
Abbreviations: CI, confidence interval; Hgb, hemoglobin; LSN, least squares mean; n, number of responders in the subgroup; NA, not applicable
What are the possible side effects?
VOYDEYA can cause hepatic enzyme increases, hyperlipidemia, and patients are to be monitored for PNH manifestations after VOYDEYA discontinuation for signs of hemolysis. The most common side effect of VOYDEYA was headache.
What are the possible side effects (results of trials used to assess safety)?
Table 4. Safety Results, Safety Population
| Adverse Reactions* | VOYDEYA N=57 n (%) |
Placebo N=29 n (%) |
|---|---|---|
| Headache | 6 (11) | 3 (10) |
| Vomiting | 4 (7) | 0 (0) |
| Pyrexia | 4 (7) | 0 (0) |
| Alanine aminotransferase increased | 3 (5) | 1 (3) |
| Hypertension | 3 (5) | 1 (3) |
| Pain in extremity | 3 (5) | 0 (0) |
Source: Adapted from VOYDEYA Prescribing Information
* Adverse reactions that occurred in ≥5% of VOYDEYA-treated patients.
Were there any differences in side effects among sex, race and age?
- Sex: The occurrence of side effects was similar in males and females.
- Race: The number of patients of races other than White was small; therefore, the occurrence of side effects of VOYDEYA could not be determined.
- Age: The occurrence of side effects was similar in patients younger and older than 45 years of age.
Were there any differences in side effects of the clinical trials among sex, race, and age groups?
The safety profile of VOYDEYA was similar among sex and age groups. There were not enough Black or African American patients included in the trials to assess a difference in race groups.
Table 5. Overview of Adverse Events by Demographic Subgroup, Safety Population, Treatment Period 1
| Characteristic | VOYDEYA N=57 n/Ns (%) |
Placebo N=29 n/Ns (%) |
Risk Difference % (95% CI) |
|---|---|---|---|
| Sex | |||
| Female | 24/34 (70.6) | 16/20 (80.0) | -9.4 (-32.7, 13.9) |
| Male | 18/23 (78.3) | 2/9 (22.2) | 56.0 (24.1, 88.0) * |
| Age group, years | |||
| <65 | 31/41 (75.6) | 15/23 (65.2) | 10.4 (-13.1, 33.9) |
| 65 to 74 | 6/9 (66.7) | 1/4 (25.0) | 41.7 (-10.8, 94.1) |
| 75 to 84 | 5/7 (71.4) | 2/2 (100) | -28.6 (-62.0, 4.9) |
| Age group ≥65, years | |||
| ≥65 | 11/16 (68.8) | 3/6 (50.0) | 18.8 (-27.3, 64.8) |
| Race | |||
| American Indian or Alaska Native | 1/1 (100) | 0/0 (NA) | NA |
| Asian | 13/22 (59.1) | 5/10 (50.0) | 9.1 (-28.1, 46.3) |
| Black or African American | 1/2 (50.0) | 0/0 (NA) | NA |
| White | 24/28 (85.7) | 8/14 (57.1) | 28.6 (-0.4, 57.6) |
| Not reported | 2/3 (66.7) | 4/4 (100) | -33.3 (-86.7, 20.0) |
| Other | 1/1 (100) | 0/0 (NA) | NA |
| Unknown | 0/0 (NA) | 1/1 (100) | NA |
| Ethnicity | |||
| Hispanic or Latino | 4/6 (66.7) | 1/1 (100) | -33.3 (-71.1, 4.4) |
| Not Hispanic or Latino | 34/46 (73.9) | 13/24 (54.2) | 19.7 (-3.9, 43.4) |
| Not reported | 4/5 (80.0) | 4/4 (100) | -20.0 (-55.1, 15.1) |
| Is in United States | |||
| United States | 6/8 (75.0) | 1/1 (100) | -25.0 (-55.0, 5.0) |
| Non-United States | 36/49 (73.5) | 17/28 (60.7) | 12.8 (-9.2, 34.7) |
Source: Adapted from FDA review
Asterisk (*) indicates that 95% confidence interval excludes zero.
Abbreviations: CI, confidence interval; N, number of patients in treatment arm; n, number of patients meeting criteria; NA, not applicable; Ns, total number of patients for each specific subgroup and were assigned to that specific arm</p>
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.
PRESCRIBING INFORMATION