Drug Trials Snapshots: IZERVAY
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 IZERVAY 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).
IZERVAY (avacincaptad pegol intravitreal solution
(ahy-zer-vey)
IVERIC bio, Inc.
Approval date: August 4, 2023
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
IZERVAY is an RNA aptamer, a PEGylated oligonucleotide that is approved for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD).
How is this drug used?
IZERVAY is a sterile, aqueous solution for intravitreal injection that is administered to each affected eye once monthly (approximately every 28±7 days).
Who participated in the clinical trials?
The FDA approved IZERVAY based on evidence from two clinical trials (OPH2003 and (ISEE2008) of 625 patients with GA secondary to AMD. The trials were conducted at 268 sites in 18 countries including the United States, Argentina, Australia, Austria, Belgium, Brazil, Canada, Colombia, Czechia, Croatia, Germany, Spain, France, Hungary, Israel, Italy, Latvia, and Poland. Of the 625 subjects, 316 (50.6%) were from the United States.
How were the trials designed?
The two trials were randomized, multi-center, double-masked, sham-controlled studies. Patient ages ranged from 51 to 97 years with a mean of 77 years. In total, 292 patients with AMD were treated with IZERVAY 2 mg, and 332 patients with AMD received sham. In both studies, the primary efficacy endpoint was the mean rate of GA growth (slope) from baseline to Month 12, measured by fundus autofluorescence evaluated at three time points: baseline, Month 6, and Month 12.
DEMOGRAPHICS SNAPSHOT
Figure 1 summarizes how many male and female patients were enrolled in the combined clinical trials used to evaluate the efficacy of IZERVAY.
Figure 1. Baseline Demographics by Sex
Source: Adapted from FDA Review
Figure 2 summarizes how many patients by race were enrolled in the combined clinical trials used to evaluate the efficacy of IZERVAY.
Figure 2. Baseline Demographics by Race
Source: Adapted from FDA Review
Figure 3 summarizes how many patients by age were enrolled in the combined clinical trials used to evaluate the efficacy of IZERVAY.
Figure 3. Baseline Demographics by Age
Source: Adapted from FDA Review
Figure 4 summarizes how many patients by ethnicity were enrolled in the combined clinical trials used to evaluate the efficacy of IZERVAY.
Figure 4. Baseline Demographics by Ethnicity
Source: Adapted from FDA Review
Who participated in the trials?
Table 1. Baseline and Demographic Characteristics, Study OPH2003, Intent-To-Treat Population
Demographic Characteristic |
Part 1 | Part 2 | Combineda | |||||
|---|---|---|---|---|---|---|---|---|
| IZERVAY 1 mg N=26 |
IZERVAY 2 mg N=25 |
Sham N=26 |
IZERVAY 2 mg N=42 |
IZERVAY 4 mg N=83 |
Sham N=84 |
IZERVAY 2 mg N=67 |
Sham N=110 |
|
| Sex, n (%) | ||||||||
| Male | 11 (42.3) | 7 (28.0) | 8 (30.8) | 15 (35.7) | 25 (30.1) | 23 (27.4) | 22 (32.8) | 31 (28.2) |
| Female | 15 (57.7) | 18 (72.0) | 18 (69.2) | 27 (64.3) | 58 (69.9) | 61 (72.6) | 45 (67.2) | 79 (71.8) |
| Ethnicity, n (%) | ||||||||
| Not Hispanic or Latino | 25 (96.2) | 24 (96.0) | 25 (96.2) | 42 (100) | 82 (98.8) | 83 (98.8) | 66 (98.5) | 108 (98.2) |
| Hispanic or Latino | 1 (3.8) | 1 (4.0) | 1 (3.8) | 0 | 1 (1.2) | 1 (1.2) | 1 (1.5) | 2 (1.8) |
| Race, n (%) | ||||||||
| American Indian or Alaska Native | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Black or African American | 0 | 0 | 0 | 0 | 0 | 1 (1.2) | 0 | 1 (0.9) |
| Asian | 1 (3.8) | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Native Hawaiian or Pacific Islander | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| White | 25 (96.2) | 25 (100) | 25 (96.2) | 42 (100) | 82 (98.8) | 82 (97.6) | 67 (100) | 107 (97.3) |
| Other | 0 | 0 | 1 (3.8) | 0 | 1 (1.2) | 1 (1.2) | 0 | 2 (1.8) |
| Age, years | ||||||||
| Mean (SD) | 73.8 (7.97) | 77.7 (9.57) | 78.1 (8.43) | 79.4 (10.65) | 79.2 (8.31) | 78.2 (8.98) | 78.8 (10.22) | 78.2 (8.82) |
| Median (Q1, Q3) | 75.5 (67.0, 79.0) |
80.0 (73.0, 86.0) |
79.0 (74.0, 85.0) |
83.0 (71.0, 87.0) |
80.0 (74.0, 86.0) |
78.0 (71.0, 83.0) |
82.0 (72.0, 87.0) |
79.0 (73.0, 83.0) |
| Min, max | 56, 91 | 58, 94 | 57, 90 | 52, 94 | 57, 95 | 54, 97 | 52, 94 | 54, 97 |
| Age group, years, n (%) | ||||||||
| <65 | 3 (11.5) | 4 (16.0) | 2 (7.7) | 6 (14.3) | 5 (6.0) | 4 (4.8) | 10 (14.9) | 6 (5.5) |
| 65 to 74 | 8 (30.8) | 5 (20.0) | 5 (19.2) | 8 (19.0) | 19 (22.9) | 22 (26.2) | 13 (19.4) | 27 (24.5) |
| 75 to 84 | 14 (53.8) | 9 (36.0) | 12 (46.2) | 12 (28.6) | 38 (45.8) | 38 (45.2) | 21 (31.3) | 50 (45.5) |
| ≥85 | 1 (3.8) | 7 (28.0) | 7 (26.9) | 16 (38.1) | 21 (25.3) | 20 (23.8) | 23 (34.3) | 27 (24.5) |
| Current smoking status, n (%) | ||||||||
| Non-active | 20 (76.9) | 15 (60.0) | 19 (73.1) | 27 (64.3) | 57 (68.7) | 55 (65.5) | 42 (62.7) | 74 (67.3) |
| Active | 6 (23.1) | 10 (40.0) | 7 (26.9) | 15 (35.7) | 26 (31.3) | 29 (34.5) | 25 (37.3) | 36 (32.7) |
| Lens status, n (%) | ||||||||
| Aphakic | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Pseudophakic | 17 (65.4) | 15 (60.0) | 16 (61.5) | 29 (69.0) | 56 (67.5) | 62 (73.8) | 44 (65.7) | 78 (70.9) |
| Phakic | 9 (34.6) | 10 (40.0) | 10 (38.5) | 13 (31.0) | 27 (32.5) | 22 (26.2) | 23 (34.3) | 32 (29.1) |
| Not done | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| If phakic, type and grade, n (%): | ||||||||
| Nuclear | ||||||||
| 0 | 4 (15.4) | 3 (12.0) | 4 (15.4) | 1 (2.4) | 3 (3.6) | 1 (1.2) | 4 (6.0) | 5 (4.5) |
| 1 | 2 (7.7) | 6 (24.0) | 5 (19.2) | 10 (23.8) | 14 (16.9) | 17 (20.2) | 16 (23.9) | 22 (20.0) |
| 2 | 3 (11.5) | 1 (4.0) | 1 (3.8) | 1 (2.4) | 10 (12.0) | 4 (4.8) | 2 (3.0) | 5 (4.5) |
| 3 | 0 | 0 | 0 | 1 (2.4) | 0 | 0 | 1 (1.5) | 0 |
| 4 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Posterior subcapsular cataract | ||||||||
| 0 | 7 (26.9) | 9 (36.0) | 9 (34.6) | 12 (28.6) | 22 (26.5) | 19 (22.6) | 21 (31.3) | 28 (25.5) |
| 1 | 1 (3.8) | 1 (4.0) | 0 | 1 (2.4) | 5 (6.0) | 3 (3.6) | 2 (3.0) | 3 (2.7) |
| 2 | 1 (3.8) | 0 | 1 (3.8) | 0 | 0 | 0 | 0 | 1 (0.9) |
| 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| 4 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Cortical | ||||||||
| 0 | 6 (23.1) | 8 (32.0) | 6 (23.1) | 10 (23.8) | 17 (20.5) | 14 (16.7) | 18 (26.9) | 20 (18.2) |
| 1 | 2 (7.7) | 2 (8.0) | 3 (11.5) | 2 (4.8) | 9 (10.8) | 5 (6.0) | 4 (6.0) | 8 (7.3) |
| 2 | 1 (3.8) | 0 | 1 (3.8) | 1 (2.4) | 1 (1.2) | 3 (3.6) | 1 (1.5) | 4 (3.6) |
| 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| 4 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Source: Adapted from FDA review
a
Abbreviations: Q1, first quartile; Q3, third quartile; SD, standard deviation
Table 2. Baseline and Demographic Characteristics, Study ISEE2008, Intent-To-Treat Population
Demographic Characteristic |
IZERVAY 2 mg N=225 |
Sham N=222 |
Total N=447 |
|---|---|---|---|
| Sex, n (%) | |||
| Male | 71 (31.6) | 66 (29.7) | 137 (30.6) |
| Female | 154 (68.4) | 156 (70.3) | 310 (69.4) |
| Ethnicity, n (%) | |||
| Not Hispanic or Latino | 168 (74.7) | 178 (80.2) | 346 (77.4) |
| Hispanic or Latino | 27 (12.0) | 23 (10.4) | 50 (11.2) |
| Not reported | 30 (13.3) | 21 (9.5) | 51 (11.4) |
| Race, n (%) | |||
| American Indian or Alaska Native | 1 (0.4) | 0 | 1 (0.2) |
| Black or African American | 0 | 1 (0.5) | 1 (0.2) |
| Asian | 1 (0.4) | 1 (0.5) | 2 (0.4) |
| Native Hawaiian or Pacific Islander | 0 | 0 | 0 |
| White | 182 (80.9) | 186 (83.8) | 368 (82.3) |
| Other | 10 (4.4) | 13 (5.9) | 23 (5.1) |
| Not reported | 31 (13.8) | 21 (9.5) | 52 (11.6) |
| Age (years) | |||
| Mean (SD) | 76.3 (8.61) | 76.7 (8.82) | 76.5 (8.71) |
| Median (Q1, Q3) | 77.0 (71.0, 83.0) | 77.0 (71.0, 83.0) | 77.0 (71.0, 83.0) |
| Min, max | 51, 93 | 51, 96 | 51, 96 |
| Age group (years), n (%) | |||
| <65 | 19 (8.4) | 20 (9.0) | 39 (8.7) |
| 65 to 74 | 72 (32.0) | 65 (29.3) | 137 (30.6) |
| 75 to 84 | 91 (40.4) | 91 (41.0) | 182 (40.7) |
| ≥85 | 43 (19.1) | 46 (20.7) | 89 (19.9) |
| Current smoking status, n (%) | |||
| Non-active | 119 (52.9) | 115 (51.8) | 234 (52.3) |
| Active | 106 (47.1) | 107 (48.2) | 213 (47.7) |
| Lens status, n (%) | |||
| Aphakic | 0 | 0 | 0 |
| Pseudophakic | 123 (54.7) | 128 (57.7) | 251 (56.2) |
| Phakic | 102 (45.3) | 94 (42.3) | 196 (43.8) |
| Not done | 0 | 0 | 0 |
| If phakic, type and grade, n (%): | |||
| Nuclear | |||
| 0 | 12 (5.3) | 8 (3.6) | 20 (4.5) |
| 1 | 62 (27.6) | 61 (27.5) | 123 (27.5) |
| 2 | 25 (11.1) | 24 (10.8) | 49 (11.0) |
| 3 | 3 (1.3) | 1 (0.5) | 4 (0.9) |
| 4 | 0 | 0 | 0 |
| Posterior subcapsular cataract | |||
| 0 | 87 (38.7) | 82 (36.9) | 169 (37.8) |
| 1 | 12 (5.3) | 9 (4.1) | 21 (4.7) |
| 2 | 3 (1.3) | 3 (1.4) | 6 (1.3) |
| 3 | 0 | 0 | 0 |
| 4 | 0 | 0 | 0 |
| Cortical | |||
| 0 | 57 (25.3) | 49 (22.1) | 106 (23.7) |
| 1 | 38 (16.9) | 40 (18.0) | 78 (17.4) |
| 2 | 7 (3.1) | 5 (2.3) | 12 (2.7) |
| 3 | 0 | 0 | 0 |
| 4 | 0 | 0 | 0 |
Source: Adapted from FDA Review
Abbreviations: Q1, first quartile; Q3, third quartile; SD, standard deviation
What are the benefits of this drug?
The results of the primary efficacy analyses in the two studies demonstrated the efficacy of IZERVAY for the treatment of GA secondary to AMD in slowing the growth of GA lesion.
What are the benefits of this drug (results of trials used to assess efficacy)?
Table 3. Mean Rate of GA Growth From Baseline, Study OPH2003
Mean Rate of Growth (Slope)1 |
IZERVAY N=67 |
Sham N=110 |
Difference (95% CI) |
|---|---|---|---|
| Month 12 | 0.283 (0.070) | 0.392 (0.068) | 0.110 (0.030, 0.190) |
| Month 18 | 0.451 (0.089) | 0.607 (0.086) | 0.156 (0.055, 0.258 |
Source: Adapted from FDA Review
1 Mean rate of growth (slope) calculated from a linear mixed effects model.
Differences are taken as Sham-IZERVAY.
Abbreviations: CI, confidence interval; GA, geographic atrophy
Table 4. Mean Rate of GA Growth From Baseline, Study ISE2008
Mean Rate of Growth (Slope)1 |
IZERVAY N=67 |
Sham N=110 |
Difference (95% CI) |
|---|---|---|---|
| Month 12 | 0.336 (0.032) | 0.392 (0.033) | 0.056 (0.016, 0.096) |
Source: Adapted from FDA Review
1 Mean rate of growth (slope) calculated from a linear mixed effects model.
Differences are taken as Sham-IZERVAY.
Abbreviations: CI, confidence interval; GA, geographic atrophy
Were there any differences in how well the drug worked in clinical trials among sex, race, and age?
- Sex: The observed effect of IZERVAY was larger for females than males. Because of limited data, this difference may be due to chance.
- Race: The number of patients of races other than White was small; therefore, differences in how IZERVAY worked among races could not be determined.
- Age: The observed effect of ZERVAY was larger for participants older than 85 years of age. Because of limited data, this difference may be due to chance.
Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?
Table 5. Efficacy Results by Sex, Race, Age, and Ethnicity, Efficacy Population
| Subgroup | IZERVAY | Sham | LS Mean Difference (CI) |
||
|---|---|---|---|---|---|
| n | Growth Rate (SE) | n | Growth Rate (SE) | ||
| Overall | 292 | 0.33 (0.03) | 332 | 0.41 (0.03) | 0.073 (0.038, 0.109) |
| Baseline GA | |||||
| <4 disc area | 224 | 0.34 (0.03) | 236 | 0.42 (0.03) | 0.060 (0.036, 0.124) |
| ≥4 disc area | 68 | 0.26 (0.08) | 96 | 0.32 (0.09) | 0.063 (0.010, 0.115) |
| Baseline VA ≥50 letters | 287 | 0.31 (0.02) | 322 | 0.38 (0.02) | 0.072 (0.036, 0.108) |
| Banded/Diffuse FAF | 278 | 0.38 (0.02) | 316 | 0.45 (0.02) | 0.069 (0.036, 0.108) |
| Age group, years | |||||
| 65 to 74 | 85 | 0.32 (0.05) | 92 | 0.34 (0.05) | 0.018 (-0.041, 0.076) |
| 75 to 84 | 112 | 0.39 (0.06) | 141 | 0.46 (0.06) | 0.067 (0.012, 0.122) |
| ≥85 | 66 | 0.31 (0.06) | 73 | 0.46 (0.06) | 0.147 (0.057, 0.236) |
| Sex | |||||
| Male | 93 | 0.27 (0.05) | 97 | 0.30 (0.05) | 0.028 (-0.029, 0.086) |
| Female | 199 | 0.34 (0.04) | 235 | 0.43 (0.03) | 0.090 (0.046, 0.135) |
| Race | |||||
| White | 249 | 0.29 (0.03) | 293 | 0.37 (0.03) | 0.083 (0.047, 0.120) |
| Ethnicity | |||||
| Not Hispanic or Latino | 234 | 0.30 (0.03) | 286 | 0.38 (0.03) | 0.078 (0.040, 0.116) |
Source: Adapted from FDA Review
* Unit for growth rate is mm/year (Square root transformed data)
Abbreviations: CI, confidence interval; FAF, fundus autofluorescence; GA, geographic atrophy; LS, least squares; SE, standard error; VA, visual acuity
What are the possible side effects?
The most common adverse reactions were conjunctival hemorrhage, increased intraocular pressure, blurred vision, and neovascular AMD.
What are the possible side effects (results of trials used to assess safety)?
Table 6. Common Ocular Adverse Reactions (≥2%) and Greater Than Sham in Study Eye, Safety Population
| Adverse Drug Reactions | IZERVAY N=292 % |
Sham N=332 % |
|---|---|---|
| Conjunctival hemorrhage | 13 | 9 |
| Increased intraocular pressure | 9 | 1 |
| Blurred vision* | 8 | 5 |
| Choroidal neovascularization | 7 | 4 |
| Eye pain | 4 | 3 |
| Vitreous floaters | 2 | <1 |
| Blepharitis | 2 | <1 |
Source: IZERVAY Prescribing Information
* Blurred vision includes visual impairment, vision blurred, visual acuity reduced, visual acuity reduced transiently
Were there any differences in side effects among sex, race and age?
Overall, the study population had a mean age of 77 years, was majority female (69%) and White (82%), which is consistent with the disease population.
- Sex: The occurrence of side effects was similar in males and females.
- Race: Because 82% of the study population was White consistent with the disease population, no conclusion can be made regarding the occurrence of side effects by race.
- Age: Because 91% of the study population was over age 65 years consistent with the disease population, no conclusion can be made regarding the occurrence of side effects based on age younger and older than 65 years of age.
Table 2. Overview of Adverse Events by Demographic Subgroup, Safety Population, Trial ISEE2008
Characteristic |
IZERVAY 2 mg N=225 n/Ns (%) |
Sham N=222 n/Ns (%) |
|---|---|---|
| Sex | ||
| Female | 118/154 (76.6) | 103/156 (66.0) |
| Male | 60/71 (84.5) | 54/66 (81.8) |
| Age group, years | ||
| <65 | 16/19 (84.2) | 11/20 (55.0) |
| 65 to 74 | 55/72 (76.4) | 45/65 (69.2) |
| 75 to 84 | 72/91 (79.1) | 66/91 (72.5) |
| ≥85 | 35/43 (81.4) | 35/46 (76.1) |
| Age group ≥65, years | ||
| ≥65 | 162/206 (78.6) | 146/202 (72.3) |
| Age group ≥75, years | ||
| ≥75 | 107/134 (79.9) | 101/137 (73.7) |
| Race | ||
| American Indian or Alaska Native | 1/1 (100) | 0/0 (NA) |
| Asian | 1/1 (100) | 1/1 (100) |
| Black or African American | 0/0 (NA) | 1/1 (100) |
| Not reported | 22/31 (71.0) | 8/21 (38.1) |
| Other | 7/10 (70.0) | 10/13 (76.9) |
| White | 147/182 (80.8) | 137/186 (73.7) |
| Ethnicity | ||
| Hispanic or Latino | 17/27 (63.0) | 18/23 (78.3) |
| Not Hispanic or Latino | 140/168 (83.3) | 131/178 (73.6) |
| Not reported | 21/30 (70.0) | 8/21 (38.1) |
| Is in United States | ||
| United States | 78/89 (87.6) | 72/92 (78.3) |
| Non-United States | 100/136 (73.5) | 85/130 (65.4) |
Source: adae.xpt; Software: R
The safety analyses of AEs were primarily based on the treatment-emergent AEs (TEAEs), which were defined as an AE occurring after the first injection on Day 1 (day of the first planned dose of study drug) and up to and including 30 days after the last dose of study drug.
Duration of Treatment: The study consisted of a total treatment period of 24 months. Monthly doses were administered at least 21 days apart.
Abbreviations: AE, adverse event; 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
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