Drug Trials Snapshots: XDEMVY
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 XDEMVY 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).
XDEMVY (lotilaner ophthalmic solution) 0.25%
Insert pronunciation
Tarsus Pharmaceuticals, Inc.
Original Approval date: July 24, 2023
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
XDEMVY is an ectoparasiticide that treats Demodex blepharitis. Blepharitis is a type of eyelid infection.
How is this drug used?
XDEMVY is a topical ophthalmic drop that is taken twice daily for six weeks.
Who participated in the clinical trials?
The FDA approved XDEMVY based on evidence from two clinical trials of 833 patients with Demodex blepharitis. The trials were conducted at 37 of sites in the United States and Mexico.
How were the trials designed?
XDEMVY was evaluated in two clinical trials (Saturn-1 and Saturn-2) of 833 patients with Demodex blepharitis. The two pivotal studies were nearly identical in design. Both studies used a randomized, controlled, multicenter, double-masked, parallel group design to assess the efficacy of XDEMVY in the treatment of Demodex blepharitis. Eligible subjects in both studies included adults (≥18 years) who had each of the following in at least one eye: >10 lashes with collarettes present on the upper eyelid (collarette score ≥2); at least mild erythema of the upper eyelid margin; and a Demodex density, upper and lower eyelids combined, of ≥1.5 mites per lash. Eligible subjects must also have had a corrected distance visual acuity better than or equal to +0.7 in each eye, as determined using the logarithm of the minimum angle of resolution and assessed with the Early Treatment Diabetic Retinopathy Study chart.
How were the trials designed?
Eligible subjects who chose to participate in the pivotal studies were randomized (1:1) to receive either XDEMVY or vehicle to be administered twice daily (morning and evening) in each eye for 43 days. Subjects were subsequently instructed to return to the study center for efficacy assessments at Days 8, 15, 22, and 43. Post-treatment follow-up visits to assess efficacy were conducted for some subjects in both studies two weeks later, at Day 57.
The efficacy variables assessed in both pivotal studies consisted of collarette and eyelid margin erythema scores for the upper eyelid of the analysis eye and counts of Demodex mites in the analysis eye. In both studies, the analysis eye was defined as the eye that met all inclusion criteria. In the case where both eyes met all criteria, the analysis eye was the eye with the highest Demodex mite density at screening or, if both eyes had equal Demodex mite densities, the right eye. In both studies, collarette and erythema grading were conducted at screening and all postbaseline study visits (i.e., Days 8, 15, 22, 43, and, where applicable, Day 57). Demodex mites were counted at screening and all postbaseline study visits beginning with Day 15 (i.e., Days 15, 22, 43, and, where applicable, Day 57). The primary endpoint in the two pivotal studies is the proportion of subjects cured based on a collarette score of 0 for the upper eyelid of the analysis eye at Day 43.
DEMOGRAPHICS SNAPSHOT
Figure 1 summarizes how many males and females were enrolled in the combined clinical trials used to evaluate the efficacy of XDEMVY.
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 XDEMVY.
Figure 2. Baseline Demographics by Race
Source: Adapted from FDA Review
Figure 3 summarizes how many patients by age were enrolled in the combined trials used to evaluate the side effects of XDEMVY.
Figure 3. Baseline Demographics by Age
Source: Adapted from FDA Review
Figure 4 summarizes how many patients by ethnicity were enrolled in the combined trials used to evaluate the side effects of XDEMVY.
Figure 4. Baseline Demographics by Ethnicity
Source: Adapted from FDA Review
Who participated in the trials?
Table 1. Demographics of Efficacy Trials by Race (Observed Data, Full Analysis Set)
| Race | Saturn-1 | Saturn-2 | Combined | ||||
| XDEMVY N=212 n (%) |
Vehicle N=209 n (%) |
XDEMVY N=212 n (%) |
Vehicle N=209 n (%) |
XDEMVY N=415 n (%) |
Vehicle N=418 n (%) |
All Subjects N=833 n (%) |
|
| White | 195 (92.0) | 187 (89.5) | 176 (86.7) | 187 (89.5) | 371 (89.4) | 374 (89.5) | 745 (89.4) |
| Black or African American | 11 (5.2) | 16 (7.7) | 20 (9.9) | 15 (7.2) | 31 (7.5) | 31 (7.4) | 62 (7.4) |
| Asian | 3 (1.4) | 2 (1.0) | 3 (1.5) | 3 (1.4) | 6 (1.4) | 5 (1.2) | 11 (1.3) |
| American Indian or Alaska Native | 1 (0.5) | 1 (0.5) | 1 (0.5) | 1 (0.5) | 2 (0.5) | 2 (0.5) | 4 (0.5) |
| Native Hawaiian or other Pacific Islander | 0 | 0 | 2 (1.0) | 0 | 2 (0.5) | 0 | 2 (0.2) |
| Multiple | 2 (0.9) | 3 (1.4) | 1 (0.5) | 0 | 3 (0.7) | 3 (0.7) | 6 (0.7) |
| Other | 0 | 0 | 0 | 3 (1.4) | 0 | 3 (0.7) | 3 (0.4) |
Source: Adapted from FDA Review
What are the benefits of this drug?
The safety and efficacy of XDEMVY for the treatment of Demodex blepharitis was evaluated in a total of 833 patients (415 of which received XDEMVY) in two 6-week, randomized, multicenter, double-masked, vehicle-controlled studies (Saturn-1 and Saturn-2). Patients with Demodex blepharitis were randomized and treated with either XDEMVY or vehicle dosed twice daily in each eye.
By Day 43, patients treated with XDEMVY had greater improvement in the Demodex infection of their eyelids (reduction of collarettes to no more than two collarettes per upper lid) compared to patients treated with vehicle in each study (Saturn-1 and Saturn-2).
What are the benefits of this drug (results of trials used to assess efficacy)?
Table 2. Summary of Efficacy Results at Day 43 for Studies Saturn-1 and Saturn-2
| Endpoint | Saturn-1 | Saturn-2 | ||
| XDEMVY N=212 n (%) |
Vehicle N=209 n (%) |
XDEMVY N=203 n (%) |
Vehicle N=209 n (%) |
|
| Primary efficacy endpoint | ||||
| Missing values imputed* | ||||
| Cured (collarette score=0), % (SE) | 43.9 (3.4) | 7.2 (1.8) | 54.7 (3.5) | 12.2 (2.3) |
| Difference in cured, % (SE)a | 36.7 (3.9) | 42.4 (4.2) | ||
| p-valueb | <0.0001 | <0.0001 | ||
| Missing values viewed as treatment failure | ||||
| Cured (collarette score=0), % (SE) | 42.9 (3.4) | 7.2 (1.8) | 53.2 (3.5) | 12.0 (2.2) |
| Difference in cured, % (SE)a | 35.7 (3.8) | 41.2 (4.2) | ||
| p-valueb | <0.0001 | <0.0001 | ||
| Secondary efficacy endpoints** | ||||
| Eradication of Demodex mites | ||||
| Cured (mite density=0), % (SE) | 67.0 (3.2) | 17.2 (2.6) | 48.8 (3.5) | 13.9 (2.4) |
| Difference in cured, % (SE)a | 49.8 (3.2) | 34.9 (4.2) | ||
| p-valueb | <0.0001 | <0.0001 | ||
| Composite cure | ||||
| Cured (collarette and erythema score=0) | 13.7 (2.4) | 1.0 (0.7) | 18.2 (2.7) | 3.8 (1.3) |
| Difference in cured, % (SE)a | 12.7 (2.5) | 14.4 (3.0) | ||
| p-valueb | <0.0001 | <0.0001 | ||
| Erythema curec | ||||
| Cured (erythema score=0), % (SE) | 18.9 (2.7) | 6.7 (1.7) | 29.6 (3.2) | 8.6 (1.9) |
| Difference in cured, % (SE)a | 12.2 (3.2) | 20.9 (3.7) | ||
| p-valueb | 0.0002 | <0.0001 | ||
Source: Adapted from FDA Review
All analyses were based on a collarette score of 0 for the upper eyelid of the analysis eye at Day 43.
* Missing values were imputed as predefined by the sponsor using the randomized study drug-based Markov Chain Monte Carlo methodology.
** Missing values viewed as treatment failure.
a The difference was computed as XDEMVY minus vehicle.
b The p-value was from a difference of proportions test
Abbreviations: SE, standard error
Figure 5. Proportion of Subjects Cured Based on a Collarette Score of 0 for the Upper Eyelid of the Analysis Eye in Saturn-1
Source: XDEMVY Prescribing Information
* Day 43 Primary Endpoint; XDEMVY N=209, Vehicle N=204, p-value <0.0001
Missing values were imputed as sponsor predefined
Figure 6. Proportion of Subjects Cured Based on a Collarette Score of 0 for the Upper Eyelid of the Analysis Eye in Saturn-2
Source: XDEMVY Prescribing Information
* Day 43 Primary Endpoint; XDEMVY N=209, Vehicle N=204, p-value <0.0001
Missing values were imputed as sponsor predefined
Were there any differences in how well the drug worked in clinical trials among sex, race and age?
- Sex: XDEMVY worked similarly in males or females.
- *Race: XDEMVY worked similarly in White and Black or African American patients.
- Age: XDEMVY worked similarly in patients younger and older than 65 years of age.
* In regard to race, no conclusions could be drawn since subjects in both studies were predominantly White (90.7% of all subjects in Saturn-1 and 88.1% of all subjects in Saturn-2).
Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?
Table 3. Subgroup Summaries of the Primary Efficacy Endpoint, Saturn-1
| Demographic | XDEMVY N=212 n/N (% [SE]) |
Vehicle N=209 n/N (% [SE]) |
| Sex | ||
| Female | 57/120 (47.5 [4.6]) | 9/114 (7.9 [2.5]) |
| Male | 35/89 (39.3 [5.2]) | 6/90 (6.7 [2.6]) |
| Age, years | ||
| <65 | 41/86 (47.7 [5.4]) | 4/62 (6.5 [3.1]) |
| ≥65 | 51/123 (41.5 [4.4]) | 11/142 (7.7 [2.2]) |
| Race | ||
| American Indian or Alaska Native | 0/1 (0) | 0/1 (0) |
| Asian | 1/3 (33.3 [27.2]) | 0/2 (0) |
| Black or African American | 5/10 (50.0 [15.8]) | 0/14 (0) |
| Multiple | 2/2 (100.0 [0.0]) | 1/3 (33.3 [27.2]) |
| White | 84/193 (43.5 [3.6]) | 14/184 (7.6 [2.0]) |
Source: Adapted from FDA Review
Abbreviations: SE, standard error
Table 4. Subgroup Summaries of the Primary Efficacy Endpoint, Saturn-2
| Demographic | XDEMVY N=212 n/N (% [SE]) |
Vehicle N=209 n/N (% [SE]) |
| Sex | ||
| Female | 53/91 (58.2 [5.2]) | 14/100 (14.0 [3.5]) |
| Male | 55/102 (53.9 [4.9]) | 11/100 (11.0 [3.1]) |
| Age, years | ||
| <65 | 47/78 (60.3 [5.5]) | 14/74 (18.9 [4.6]) |
| ≥65 | 61/115 (53.0 [4.7]) | 11/126 (8.7 [2.5]) |
| Race | ||
| White | 99/167 (59.3 [3.8]) | 20/179 (11.2 [2.4]) |
| Other | 9/26 (34.6 [3.8]) | 5/21 (23.8 [2.4]) |
Source: Adapted from FDA Review
Abbreviations: SE, standard error
What are the possible side effects?
The most common ocular adverse reaction observed in controlled clinical studies with XDEMVY was instillation site stinging and burning which was reported in 10% of patients. Other ocular adverse reactions reported in less than 2% of patients were chalazion or hordeolum and punctate keratitis.
What are the possible side effects (results of trials used to assess safety)?
Table 5. Overview of Adverse Reactions by Sex, Age, Race, Ethnicity, and Country in Patients in Saturn-1 and Saturn-2
| Demographic | XDEMVY N=415 |
Vehicle N=418 |
All Grades XDEMVY N=415 n/Ns (%) |
All Grades Vehicle N=418 n/Ns (%) |
Grades 3 to 4 XDEMVY N=415 n/Ns (%) |
Grades 3 to 4 Vehicle N=418 n/Ns (%) |
| Sex, n (%) | ||||||
| Female | 220 (53.0) | 220 (52.6) | 72/220 (32.7) | 65/220 (29.5) | 3/220 (1.4) | 1/220 (0.5) |
| Male | 195 (47.0) | 198 (47.4) | 55/195 (28.2) | 47/198 (23.7) | 2/195 (1.0) | 2/198 (1.0) |
| Age group, years, n (%) | ||||||
| 18 to <65 years | 170 (41.0) | 145 (34.7) | 0/2 (0) | 0/2 (0) | 0/2 (0) | 0/2 (0) |
| ≥65 years | 245 (59.0) | 273 (65.3) | 2/6 (33.3) | 0/5 (0) | 0/6 (0) | 0/5 (0) |
| Race, n (%) | ||||||
| American Indian or Alaska Native | 2 (0.5) | 2 (0.5) | 0/2 (0) | 0/2 (0) | 0/2 (0) | 0/2 (0) |
| Asian | 6 (1.4) | 5 (1.2) | 2/6 (33.3) | 0/5 (0) | 0/6 (0) | 0/5 (0) |
| Black or African American | 31 (7.5) | 31 (7.4) | 8/31 (25.8) | 10/31 (32.3) | 1/31 (3.2) | 0/31 (0) |
| Multiple | 3 (0.7) | 3 (0.7) | 2/3 (66.7) | 1/3 (33.3) | 0/3 (0) | 0/3 (0) |
| Native Hawaiian or Other Pacific Islander | 2 (0.5) | 0 (0) | 0/2 (0) | 0/0 (NA) | 0/2 (0) | 0/0 (NA) |
| Other | 0 (0) | 3 (0.7) | 0/0 (NA) | 1/3 (33.3) | 0/0 (NA) | 0/3 (0) |
| White | 371 (89.4) | 374 (89.5) | 115/371 (31.0) | 100/374 (26.7) | 4/371 (1.1) | 3/374 (0.8) |
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 occurrence of side effects was similar in White and Black or African American patients.
- Age: The occurrence of side effects was similar in patients younger and older than 65 years of age.
Were there any differences in side effects of the clinical trials among sex, race, and age groups?
Table 6. Overview of Adverse Reactions by Sex, Age, Race, Ethnicity, and Country in Patients in Saturn-1 and Saturn-2
| Demographic | XDEMVY N=415 |
Vehicle N=418 |
All Grades XDEMVY N=415 n/Ns (%) |
All Grades Vehicle N=418 n/Ns (%) |
Grades 3 to 4 XDEMVY N=415 n/Ns (%) |
Grades 3 to 4 Vehicle N=418 n/Ns (%) |
| Sex, n (%) | ||||||
| Female | 220 (53.0) | 220 (52.6) | 72/220 (32.7) | 65/220 (29.5) | 3/220 (1.4) | 1/220 (0.5) |
| Male | 195 (47.0) | 198 (47.4) | 55/195 (28.2) | 47/198 (23.7) | 2/195 (1.0) | 2/198 (1.0) |
| Age group, years, n (%) | ||||||
| 18 to <65 years | 170 (41.0) | 145 (34.7) | 0/2 (0) | 0/2 (0) | 0/2 (0) | 0/2 (0) |
| ≥65 years | 245 (59.0) | 273 (65.3) | 2/6 (33.3) | 0/5 (0) | 0/6 (0) | 0/5 (0) |
| Race, n (%) | ||||||
| American Indian or Alaska Native | 2 (0.5) | 2 (0.5) | 0/2 (0) | 0/2 (0) | 0/2 (0) | 0/2 (0) |
| Asian | 6 (1.4) | 5 (1.2) | 2/6 (33.3) | 0/5 (0) | 0/6 (0) | 0/5 (0) |
| Black or African American | 31 (7.5) | 31 (7.4) | 8/31 (25.8) | 10/31 (32.3) | 1/31 (3.2) | 0/31 (0) |
| Multiple | 3 (0.7) | 3 (0.7) | 2/3 (66.7) | 1/3 (33.3) | 0/3 (0) | 0/3 (0) |
| Native Hawaiian or Other Pacific Islander | 2 (0.5) | 0 (0) | 0/2 (0) | 0/0 (NA) | 0/2 (0) | 0/0 (NA) |
| Other | 0 (0) | 3 (0.7) | 0/0 (NA) | 1/3 (33.3) | 0/0 (NA) | 0/3 (0) |
| White | 371 (89.4) | 374 (89.5) | 115/371 (31.0) | 100/374 (26.7) | 4/371 (1.1) | 3/374 (0.8) |
| Ethnicity, n (%) | ||||||
| Hispanic or Latino | 31 (7.5) | 28 (6.7) | 9/31 (29.0) | 10/28 (35.7) | 2/31 (6.5) | 1/28 (3.6) |
| Not Hispanic or Latino | 384 (92.5) | 390 (93.3) | 118/384 (30.7) | 102/390 (26.2) | 3/384 (0.8) | 2/390 (0.5) |
| Country of participation, n (%) | ||||||
| USA | 415 (100) | 418 (100) | 127/415 (30.6) | 112/418 (26.8) | 5/415 (1.2) | 3/418 (0.7) |
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
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.