Motugivatrep 0.3% ophthalmic suspension alone and in combination with existing dry eye therapies may be well tolerated over 52 weeks among patients with dry eye disease.
In the multicenter, open-label, single-arm phase 3 study, researchers enrolled 162 adult patients with dry eye disease at 22 clinics in Japan between January 2023 and May 2024. Eligible patients had experienced symptoms for at least 6 months and met prespecified criteria for symptom severity and tear break-up time. Patients received 1 drop of motugivatrep 0.3% ophthalmic suspension in each eye 4 times daily for 52 weeks. Among them, 105 received monotherapy, while 57 received motugivatrep alongside diquafosol sodium, rebamipide, or sodium hyaluronate. Overall, 149 patients completed treatment.
The primary outcomes were the incidence and severity of treatment-emergent adverse events (TEAE) and treatment-related adverse events (TRAE). Additional safety assessments included ophthalmic examinations, vital signs, and laboratory testing. Clinical outcomes included the Dry Eye-Related Quality-of-Life Score (DEQS), visual analog scale scores for eye dryness, 5-item Dry Eye Questionnaire scores, corneal fluorescein staining (CFS), tear break-up time (TBUT), conjunctival fluorescein staining, and tear secretion.
TEAEs occurred in 73 patients (45%), including 41 (39%) receiving monotherapy and 32 (56%) receiving combination therapy. TRAEs were reported in 24 patients (15%) overall, including 13 (12%) and 11 (19%), respectively. Most TRAEs were mild, and no severe or serious TRAEs were reported. Three patients experienced serious TEAEs, all considered unrelated to treatment. No mortality occurred.
The most frequently reported ocular TRAE was eye discharge in 5 patients (3%), while feeling cold was the most common nonocular TRAE in 12 patients (7%). One patient receiving combination therapy experienced 3 moderate TRAEs that resolved following treatment discontinuation. Three patients discontinued treatment because of TEAEs, including 1 whose events were considered treatment-related.
Patient-reported symptoms improved early and remained below baseline levels throughout treatment. The mean DEQS total score decreased by 22.18 points from a baseline of 37.61 at week 52. Improvements in DEQS and eye dryness scores were observed by day 8 and were maintained through day 365. Scores on the 5-item Dry Eye Questionnaire improved during treatment.
Objective ocular surface assessments showed similar trends. Mean total CFS scores improved from baseline by day 15, with reductions stabilizing after day 57 and persisting through week 52. Mean TBUT increased from baseline by day 15 and continued to improve through day 365. Conjunctival fluorescein staining scores improved, although tear secretion decreased from baseline during treatment.
Among 28 patients with moderate-to-severe corneal epithelial abnormalities at baseline, including 15 receiving monotherapy and 13 receiving combination therapy, reductions in CFS scores were greater than those observed in the overall study population at each assessment. Improvements in corneal staining followed similar patterns across the treatment groups.
Patients receiving combination therapy demonstrated improvements in subjective symptoms and objective ocular surface measures. At day 365, the combination group had a mean DEQS reduction of 20.74 points, a 42.6-point reduction in eye dryness scores, a 1.9-point reduction in CFS scores, and a 0.732-second increase in TBUT. Improvements were observed across the 3 concomitant medication subgroups, although the study was not designed to establish comparative efficacy between treatment approaches.
Long-term safety evaluations identified no clinically meaningful changes in ophthalmic examinations, vital signs, or laboratory measures. Hyperthermia was not reported as a treatment-related event.
The study had several limitations. Its open-label, single-arm design lacked a concurrent placebo or active comparator, preventing definitive attribution of symptom improvements to motugivatrep. Unmasked symptom assessments and the potential influence of medication washout prior to baseline may have affected the observed changes. The study enrolled patients in Japan, most of whom had relatively mild corneal staining at baseline, potentially limiting generalizability to patients with more severe disease or other populations. The combination therapy subgroups were small, and the concomitant medications reflected regional treatment practices.
"Motugivatrep 0.3% ophthalmic suspension administered QID was well tolerated over 52 weeks with clinical outcomes consistent with a treatment effect, whether used alone or in combination with standard [dry eye disease] therapies,” wrote lead study author Yuichi Hori, of Toho University Faculty of Medicine in Japan, and colleagues.
Full disclosures of the study authors can be found in the study.
Source: Clinical Ophthalmology
