Findings from an extension of the Saturn-1 clinical trial published in Cornea assessed the long-term outcomes of lotilaner ophthalmic solution, 0.25%, to treat Demodex blepharitis (DB).
Give me some background.
DB is a lid margin disease with an estimated prevalence of 55-58% in patients seeking eye care in the United States.
It is caused by an overpopulation (demodicosis) of Demodex mites, resulting in collarettes—a pathognomonic sign of DB that can be visualized during routine and slit lamp examinations.
Current therapies for DB include tea tree oil (TTO)-based treatments and XDEMVY, a topical lotilaner ophthalmic solution 0.25% from Tarsus Pharmaceuticals that was approved by the FDA and launched in 2023 to treat DB.
How does lotilaner treat Demodex blepharitis?
Lotilaner eradicates Demodex mites by selectively inhibiting their gamma-aminobutyric acid (GABA)-gated chloride channels—resulting in spastic paralysis.
The 6-week treatment includes at least two mite life cycles to ensure a meaningful reduction of mite density.
Talk about the Saturn-1 and Saturn-2 studies.
Both the Saturn-1 (NCT04475432) and Saturn-2 (NCT04784091) studies were randomized, controlled, multicenter, double-masked phase 3 trials that compared the safety and efficacy of lotilaner ophthalmic solution, 0.25% to vehicle control for 6 weeks of treatment for DB.
Between both studies, a total of 833 patients aged 18 years and above were included and investigators found that lotilaner had a positive safety profile to treat DB, however they did not assess its long-term safety—motivating researchers to perform an extension study.
Now this extension study.
In this observational extension study, investigators included 239 DB patients—with 57% of participants from Saturn-1—who completed the original study and presented for the 180-day visit.
All participants were evaluated at days 180 and 365 after the start of a 6-week treatment with the study drug or its vehicle.
Findings?
The proportion of patients with 0-2 collarettes (grade 0) was significantly higher in the study group (239 patients) than the control group (111 patients).
When comparing the study and control groups, this broke down to:
- Day 180
- 39.8% vs. 2.7%
- Day 365
- 23.5% vs. 2.9% (P<0.0001)
Tell me more.
Additionally, the proportion of patients with <10 collarettes (collarette grade 0-1) in the treatment arm was significantly higher than in the control arm.
At day 180 the ratio of patients with <10 collarettes was 70.3% vs. 18.0% and 62.6% vs. 21.9% at day 365 for the study and control groups, respectively (P<0.0001).
Anything else?
Erythema improved even after the completion of the 6-week lotilaner treatment in the treatment arm.
At day 180 in the treatment arm 21.1% of patients achieved an erythema cure (grade 0), and at day 365 this increased to 28.7%, compared to 6.3% and 14.3% in the control arm, respectively.
Further, no serious ocular adverse events (AEs) were observed in the study group; while there was one treatment-related ocular AE (blurred vision), it was considered mild.
Expert opinion?
The percentage of patients with 0-2 collarettes (grade 0) progressively decreased from 44% at the conclusion of the precursor study (week 6) to 40% at day 180 and 24% at day 365.
According to the study authors, “It is possible that a relatively small number of mites escaped the acaricidal effect of lotilaner or that mites from other areas of the face or external locations reinfested the eyelash follicles, leading to a reduction in the proportion of patients with 0-2 collarettes (grade 0) at the day 365 time point.”
As such, collarettes returning in some patients over time is to be expected.
Take home.
After 6-week treatment with lotilaner ophthalmic solution, 0.25% for DB, no long-term concerns were reported during the 1-year follow-up period.
A notable proportion of patients with 0-2 collarettes (grade 0) or <10 collarettes (grade 0 or 1) was observed during the 1-year follow-up—suggesting a durable and long-term treatment effect of lotilaner ophthalmic solution, 0.25% for DB, even after treatment is completed.
The study authors recommended that future studies compare the safety and efficacy of lotilaner to current TTO-based treatments.