Perfluorohexyloctane Eye Drops for Dry Eye Disease Associated With Meibomian Gland Dysfunction in Chinese Patients

Abstract

ImportanceMeibomian gland dysfunction (MGD) is a leading cause of evaporative dry eye disease (DED). Medical and surgical management for DED is limited; therefore, new treatment options are sought.ObjectiveTo evaluate the efficacy and safety of SHR8058 (perfluorohexyloctane) eye drops in Chinese patients with DED associated with MGD through 57 days.Design, Setting, and ParticipantsThis was a randomized, multicenter, double-masked, saline-controlled, phase 3 clinical trial conducted from February 4, 2021, to September 7, 2022. Patients were recruited from the departments of ophthalmology in 15 hospitals in China. Patients with DED associated with MGD were enrolled between February 4 and July 1, 2021. The diagnosis was based on patient complaint of DED symptoms, an ocular surface disease index of 25 or higher, tear film break-up time of 5 seconds or less, Schirmer I test without anesthesia results of 5 mm or more at 5 minutes, total corneal fluorescein staining (tCFS) score of 4 to 11, and an MGD score of 3 or higher.InterventionsEligible participants were randomly assigned 1:1 to receive perfluorohexyloctane eye drops or 0.6% sodium chloride [NaCl]) 4 times per day.Main Outcomes and MeasuresThe primary end points were the changes from baseline in tCFS and eye dryness scores at day 57.ResultsA total of 312 participants were included in the analysis: 156 (mean [SD] age, 45.4 [15.2] years; 118 female [75.6%]) in the perfluorohexyloctane group and 156 (mean [SD] age, 43.7 [15.1] years; 127 female [81.4%]) in the NaCl group. Both primary end points were achieved, ie, changes from baseline at day 57 of tCFS score (mean [SD], −3.8 [2.7] vs −2.7 [2.8]) and eye dryness score (mean [SD], −38.6 [21.9] vs −28.3 [20.8]) in the perfluorohexyloctane group were superior to the control group, with estimated mean differences of −1.14 (95% CI, −1.70 to −0.57; P < .001) and −12.74 (95% CI, −17.20 to −8.28, P < .001), respectively. Improvements on both end points appeared to be noted on day 29 and day 15, respectively, and maintained through day 57. Compared with the control, perfluorohexyloctane eye drops also alleviated symptoms including pain (mean [SD] tCFS score, 26.7 [23.7] vs −18.7 [22.5]; P = .003), awareness of DED symptoms (mean [SD] tCFS score, −38.1 [25.1] vs −23.7 [27.6]; P < .001), and frequency of dryness (mean [SD] tCFS score, −43.3 [23.8] vs −29.1 [24.8]; P < .001). Treatment-emergent adverse events occurred in 34 participants (21.8%) and 40 participants (25.6%) in the perfluorohexyloctane and control groups, respectively.Conclusions and RelevanceResults of this randomized clinical trial demonstrate that perfluorohexyloctane eye drops significantly ameliorated the signs and symptoms of DED associated with MGD with a rapid efficacy as well as satisfactory tolerability and safety through 57 days. Findings support the use of these eye drops if results can be confirmed independently and over longer time periods.Trial RegistrationClinicalTrials.gov Identifier: NCT05515471

Long-Term Safety and Efficacy of Perfluorohexyloctane Ophthalmic Solution for the Treatment of Patients With Dry Eye Disease: The KALAHARI Study

“…Short-term efficacy and safety were consistently demonstrated in the 8-week phase 2 SEECASE, phase 3 GOBI, and phase 3 MOJAVE studies, as well as a phase 3 study conducted in China, in patients with DED associated with MGD. 18 – 21 In KALAHARI, patients were administered PFHO for 52 weeks; thus, patients who were randomized to PFHO in GOBI were exposed to a cumulative 60 weeks of PFHO treatment during the combined GOBI and KALAHARI study periods. Long-term use of PFHO 4 times daily was safe and well tolerated in patients in the KALAHARI study, with a safety profile consistent with that reported in previous short-term studies of PFHO.…”

“…Long-term use of PFHO 4 times daily was safe and well tolerated in patients in the KALAHARI study, with a safety profile consistent with that reported in previous short-term studies of PFHO. 18 – 21 During the year-long treatment period, no single ocular AE occurred at an incidence ≥2.0%, and ocular AEs were considered treatment-related in fewer than half of the patients. There was a low rate of instillation site reaction in this study (1.0%), which confirms the favorable tolerability previously reported.…”

“…There was a low rate of instillation site reaction in this study (1.0%), which confirms the favorable tolerability previously reported. 18 – 21 PFHO has been designed to be well tolerated; it is a single-ingredient product that requires no preservatives and has a small drop size—all important characteristics for the chronic treatment of patients with DED. Furthermore, because PFHO is a nonaqueous drop, it does not have a pH; therefore, instillation of PFHO is not expected to cause a burning sensation, as has been observed for topical ocular products with a pH outside the physiological range.…”

“… 19 , 20 The efficacy of PFHO in improving both signs and symptoms of DED was also demonstrated in a randomized, double-masked, saline-controlled study in Chinese patients with DED associated with MGD. 21 PFHO had a favorable safety profile and was well tolerated by patients in all these clinical studies. 18 – 21 Although PFHO has demonstrated efficacy and safety in these 8-week studies, 18 – 21 DED is a chronic disease, and patients require long-term management.…”

“… 21 PFHO had a favorable safety profile and was well tolerated by patients in all these clinical studies. 18 – 21 Although PFHO has demonstrated efficacy and safety in these 8-week studies, 18 – 21 DED is a chronic disease, and patients require long-term management. The objective of this open-label extension study (KALAHARI) was to evaluate the long-term safety and efficacy of PFHO in a subset of patients who continued to use PFHO or switched from hypotonic saline to PFHO after completing the phase 3 GOBI study.…”