On this episode of Interventional Mindset, Preeya K. Gupta, MD, is joined by Damon Dierker, OD, FAAO, to review new data on the efficacy of XDEMVY (lotilaner ophthalmic solution 0.25%, Tarsus Pharmaceuticals) for the treatment of Demodex blepharitis (DB) in patients with concurrent meibomian gland dysfunction (MGD).
Dr. Dierker is the Director of Optometric Services at Eye Surgeons of Indiana in Indianapolis, Indiana, and an adjunct faculty member at the Indiana University School of Optometry.
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What is Demodex blepharitis?
Demodex blepharitis is a common lid margin disease caused by the overpopulation of Demodex mites that can result in collarettes forming at the base of eyelashes.1 Collarettes are made up of the waste from these mites in the form of follicular dandruff and lipids. Of note, collarettes are a pathognomonic sign of DB that can be visualized by having patients look down and checking their lash line during routine and slit lamp examinations.
Additional symptoms DB patients may report include:1
- Discomfort
- Eyelid redness
- Dryness
- Itching
- Burning
- Fluctuating vision
Concomitant DB and MGD
Beyond the lid margin, DB can impact the overall ocular surface as well and has been associated with anterior and posterior blepharitis, MGD, ocular rosacea, and keratitis.2 In fact, the presence of Demodex brevis (one of two mite species found on or in the lid margin) has been implicated in MGD, including meibomian gland loss.
It is believed that the buildup of decomposing mite remains contributes to the physical blockage of the meibomian glands, potentially leading to changes in gland architecture over time.2 Subsequently, the changes in meibum secretion or lipid composition in MGD may worsen this cycle by making the ocular environment more favorable for Demodex and initiating a chronic inflammatory process.
Considering that an estimated 55 to 58% of patients seeking eyecare in the United States show signs of DB,3-5 and a 60% prevalence of Demodex has been reported in the lashes of MGD patients (compared to 18% in control subjects free of lid and margin disease),2 there is a need for an effective treatment for patients with both conditions.
Enter XDEMVY
XDEMVY was approved by the FDA in July 2023 with an indication for the treatment of Demodex blepharitis.6 The recommended dosage of XDEMVY is one drop in each eye twice daily (BID) for 6 weeks.
In two phase 2 clinical trials (SATURN-1 [NCT04475432] and SATURN-2 [NCT04784091]), XDEMVY significantly improved DB through three primary endpoints:7-10
- Mite eradication: 60% of patients taking XDEMVY achieved complete mite eradication, defined as 0 mites per lash, compared to 16% of patients taking the vehicle.
- Collarette reduction: 50% of patients taking XDEMVY had complete collarette cure defined as <2 collarettes on the upper lid compared to 10% of patients taking the vehicle.
- Clinically meaningful collarette cure was defined as <10 collarettes and was reported in 85% of patients taking XDEMVY compared to 28% of patients taking the vehicle.
- Improvement of eyelid erythema: 25% of patients taking XDEMVY exhibited erythema cure defined as grade 0 or no lid margin erythema on a 0 to 3 scale compared to 8% of patients taking the vehicle.
Both clinical trials compared the safety and efficacy of lotilaner ophthalmic solution to vehicle control for 6 weeks of treatment for DB.6 Between the two studies, a total of 833 patients aged 18 years and older were included and the findings demonstrated that lotilaner had a positive safety profile to treat DB.10 Further, a 1-year extension study from SATURN-1 showed a potentially durable treatment effect and no serious ocular adverse events.11
New data on XDEMVY’s impact on concurrent DB and MGD
Tarsus Pharmaceuticals announced new data from the phase 2 ERSA (NCT05454956) and RHEA clinical trials during the 2024 American Academy of Optometry’s (AAOpt) annual meeting.12 Both studies were pooled for analysis after establishing a between-group baseline equivalence.
The endpoints for both studies included:12
- Safety assessments
- Lower lid meibomian gland secretion score (MGSS)
- DB endpoints (collarette and erythema reduction)
- Dry eye symptoms using a visual analog scale (VAS, 0 to 100) on:
- Eye dryness
- Ocular discomfort
- Fluctuating vision
- Burning
- Itching
- Redness
Table 1: Comparison of the phase 2 ERSA and RHEA trials for lotilaner ophthalmic solution 0.25%.12
| Trial | Study Design | Purpose | Participants | Setup |
|---|---|---|---|---|
| ERSA | Randomized, two-arm, double-masked study | To evaluate the safety and efficacy of BID vs. TID dosing schedules of lotilaner in DB patients with MGD | 39 patients (aged 18 and older, average age 63.7 years) | Cohort 1: BID dosing of XDEMVY, Cohort 2: TID dosing of XDEMVY |
| RHEA | Randomized vehicle study | To assess the efficacy of the vehicle on DB patients with MGD | 40 patients (average age 63.4 years) | Cohort 1: TID dosing for the first 15 days, then BID until day 85, Cohort 2: BID for 85 days, Cohort 3: TID for 85 days |
Table 1: Courtesy of Alexandra Delaney-Gesing.
Findings from the pooled analysis of ERSA and RHEA
Tarsus reported statistically significant improvements from baseline at days 43 and 85 for the following categories:12
- Mean MGSS
- Lotilaner 0.25% group
- Baseline: 21.9
- Day 43: 27.8
- Day 85: 33.2
- Vehicle group
- Baseline: 22.1
- Day 43: 23.3
- Day 85: 23.1
- Lotilaner 0.25% group
- Percentage of patients achieving ≥3 glands with improvement to clear meibum
- Lotilaner 0.25% group
- Day 43: 44.7%
- Day 85: 78.9%
- Vehicle group
- Day 43: 17.6%
- Day 85: 18.1%
- Lotilaner 0.25% group
- The mean number of glands secreting any liquid
There were also notable improvements in terms of DB endpoints and dry eye symptoms, such as:12
- Collarette reduction (down to grade 0 [i.e., 0 to 2 collarettes per lid])
- Lotilaner 0.25% group
- Day 43: 42%
- Day 85: 66%
- Vehicle group
- Day 43: 0%
- Day 85: 0%
- Lotilaner 0.25% group
- DB and dry eye symptom reduction
- Burning (measured in VAS score)
- Lotilaner 0.25% group
- Baseline: 35.4
- Day 43: 20.0
- Day 85: 10.5
- Vehicle group
- Baseline: 46.0
- Day 43: 34.8
- Day 85: 31.6
- Lotilaner 0.25% group
- Fluctuating vision (measured in VAS score)
- Lotilaner 0.25% group
- Baseline: 35.4
- Day 43: 20.0
- Day 85: 10.5
- Vehicle group
- Baseline: 46.0
- Day 43: 34.8
- Day 85: 31.6
- Lotilaner 0.25% group
- Burning (measured in VAS score)
Similar improvements were reported for itching, eyelid erythema, and redness, and no serious treatment-related adverse events were observed in either of the studies, noted Dr. Dierker. In total, 5.1% (two patients) and 15% (six patients) in the ERSA and RHEA studies, respectively, reported having treatment-related ocular adverse events.12
Dr. Dierker explained that his takeaways from the pooled analysis of ERSA and RHEA are that BID dosing is optimal, as TID dosing did not have a significant difference in treatment effect, and that DB patients with MGD can be confidently told that they will likely have improvements in both DB symptoms and meibomian gland function (particularly in the form of decreased gland obstruction and better secretion quality).
For a deeper dive into the findings from ERSA and RHEA, check out the Glance story, Tarsus releases new phase 2 data on TP-03 for MGD!
Clinical pearls for treating patients with concurrent DB and MGD
If a patient reports feeling itchiness, Dr. Dierker asks them to point out where the itchiness is most intense, and if it is along their lash line, DB is likely a contributing factor.
As it is common for ocular surface disease (OSD) patients to have coexisting DB, Dr. Dierker prefers to ask these patients specific questions about their symptoms, such as:
- How are your eyes bothering you?
- Do you feel the need to use eye drops regularly?
- Are your eyes ever red?
- Do you have fluctuating vision?
He also utilizes the Standardized Patient Evaluation of Eye Dryness (SPEED) questionnaire, and if he suspects that a patient may have DB, he asks them to look down and then evaluates their lash line for collarettes. If there are many collarettes present, DB is a straightforward diagnosis, and pending any contraindications, XDEMVY is his go-to prescription.
For patients with few collarettes and concurrent MGD, he opts to aggressively treat both with XDEMVY, typically even before considering other interventions for MGD, such as thermal pulsation, intense pulsed light (IPL), or chronic topic immunomodulatory therapy, to effectively address the symptoms of both conditions within 6 weeks.
To learn more about how physicians can identify DB and MGD and discuss XDEMVY with patients, watch the full interview!
Conclusion
Considering that both DB and MGD are relatively common conditions and can be concomitant in OSD patients, the new data on XDEMVY’s efficacy for the treatment of MGD symptoms offers physicians a potential “two birds, one stone” treatment option.
In particular, XDEMVY has the potential to improve objective measures of MGD and provide meaningful changes in DB and MGD symptoms, such as fluctuating vision and itching.12
