Game Changer for Presbyopia?

Optimised pilocarpine drop shows promise for presbyopia. Cheryl Guttman Krader reports from ASCRS 2021 in Las Vegas, USA. AGN-190584, a topical optimised formulation of pilocarpine HCl 1.25%, is a safe, well-tolerated, and effective treatment for presbyopia, suggest the results of GEMINI 1, a phase 3 vehicle-controlled study. As reported in a series of presentations at the conference, the findings showed AGN-190584 was associated with statistically significant and clinically meaningful improvements in near and intermediate vision in addition to high patient satisfaction. Moreover, it did not compromise distance vision. “Marketing approval of AGN-190584 will be a milestone event, and its availability will be a big-time game changer for our patients,” George O Waring IV, MD said. The GEMINI 1 study was a multicentre, double-masked trial that randomised 323 patients aged 40 to 55 years in a one-to-one ratio to AGN-190584 or vehicle administered once daily, bilaterally, for 30 days. “Patients with severe dry eye were excluded, but those with a history of previous LASIK or PRK were encouraged to participate. Remarkably, 99% of patients in the AGN-190584 group and 96% of controls completed the study that involved marathon-length study visits,” William C Christie MD reported. EFFICACY DATA The GEMINI 1 study met its primary endpoint. The percentage of participants with at least three lines of improvement or better in mesopic distance-corrected near visual acuity (DCNVA) at three hours post-administration on day 30 was significantly greater with AGN-190584 treatment compared to vehicle. A post-hoc analysis also showed no participants with less than a three-line improvement reported more than a five-letter loss in mesopic, corrected distance visual acuity (CDVA) on day 30, hour three. AGN-190584 also demonstrated statistical superiority to vehicle for the key secondary endpoint analysing the percentage of participants with at least three lines or better improvement in mesopic DCNVA at six hours post dosing. Data for other efficacy endpoints showed statistically significant differences favouring AGN-190584 versus vehicle for increasing the percentage of participants achieving 20/40 or better in DCNVA. Researchers observed a significant difference in the two-line or greater gain in mesopic, high-contrast binocular DCNVA. Significant treatment benefits were also observed for improvements in measures of distance-corrected intermediate acuity (DCIVA). PUPIL MEASUREMENTS Pupil measurement data showed the onset and duration of improvement in mesopic DCNVA corresponded with the onset and duration of change in pupil size. Change in pupil diameter mirrored improvement in DCNVA with onset at 15 minutes. Pupil diameter returned to baseline within 24 hours after the last drop. The pupillary response to light after AGN-190584 treatment was maintained under mesopic and photopic conditions, and its response to AGN-190584 remained consistent from day 1 to day 30, David C Wirta MD reported. “The latter finding is important for showing there was no tachyphylaxis to AGN-190584,” he said. PATIENT-REPORTED OUTCOMES Questionnaires used to collect patient-reported outcomes included the Near Vision Presbyopia Task Questionnaire (NVPTQ) based on reading a book, newspaper, menu, and nutrition label. GEMINI 1 met the prespecified secondary endpoints evaluating mean change from baseline in mesopic NVPTQ performance and satisfaction at day 30, hour three. Additional analyses showed AGN-190584 significantly improved photopic NVPTQ performance and patient satisfaction. Dr Wirta presented results from the Presbyopia Impact and Coping Questionnaire that showed AGN-190584 was associated with statistically significant reductions in presbyopia impact and frequency of compensatory coping behaviours, such as squinting or changing font size, compared to the vehicle group. Results from the Presbyopia Patient Satisfaction Questionnaire showed that compared to controls, the AGN- 190584 patients were significantly more satisfied with aspects of their treatment. SAFETY On average, “Loss of distance vision was not observed. In fact, there was a slight improvement in the mean distance vision in the AGN-190584 group relative to the control group at many of the timepoints during the study,” said Dr Waring, who attributed the finding to the optical effect of a small aperture. Headache was the most common adverse event in both the AGN-190584 (14.1%) and control (9.4%) groups. Dr Waring observed patients were prompted to report headache because it is a potential concern with ophthalmic pilocarpine. “There were no severe headaches or discontinuations for headache in the AGN-190584 group. Headaches were mostly mild, transient, and did not require treatment,” he reported. George O Waring IV, MD, FACS is the founder and Medical Director of the Waring Vision Institute in Mt. Pleasant, South Carolina, USA. gwaring@waringvision.com William C Christie MD practices in Cranberry Township, Pennsylvania, USA. info@scottandchristie.com David C Wirta MD practices in Newport Beach, California, USA. david.wirta@drwirta.com