Latanoprost with high precision, piezo-print microdose delivery for IOP lowering: clinical results of the PG21 study of 0.4 µg daily microdose

Abstract

Louis R Pasquale,1 Shan Lin,2 Robert N Weinreb,3 James C Tsai,4 Robert L Kramm,5 Tsontcho Ianchulev5,6 1Department of Ophthalmology, Harvard Medical School, Cambridge, MA, USA; 2Department of Ophthalmology, University of California San Francisco, San Francisco, CA, USA; 3Department of Ophthalmology, University of California San Diego, San Diego, CA, USA; 4Department of Ophthalmology, Mount Sinai School of Medicine, New York, NY, USA; 5Eyenovia Incorporated, New York, NY, USA; 6Department of Ophthalmology, New York Eye and Ear Infirmary, Mount Sinai Medical School, New York, NY, USA Background: Topical high-precision piezo-print delivery of microdoses of latanoprost achieved significant IOP reduction consistent with the eyedropper effect but with a 75% reduced exposure to drugs and preservatives. Prostaglandin analogs are a mainstay glaucoma therapy. However, conventional eyedroppers deliver 30–50 μL drops that greatly exceed the physiologic 7-μL ocular tear film capacity. Eyedropper overdosing floods the eye with excess drug compounds and preservatives, resulting in ocular surface toxicity, periorbitopathy, and other well-characterized ocular side effects. Piezoelectric high-precision microdosing provides targeted delivery that can reduce exposure to both drug and preservatives compared to conventional eyedropper delivery, with the potential to deliver similar biologic effect. Methods: Both eyes (N=60) of 30 healthy volunteers received single 8-μL microdoses of 0.005% latanoprost (0.4 μg; μRx-latanoprost) on the morning of Days 1 and 2 using a high-precision, piezo-print horizontal delivery system. Diurnal IOP was measured before and 2 days after microdosing. Main efficacy outcomes were diurnal IOP change after μRx-latanoprost microdosing and accurate microdosing success rates, and the primary safety outcome was adverse event (AE) incidence. Results: μRx-latanoprost reduced baseline IOP by 26% and 30% at 1 and 2 days postadministration, respectively. Successful topical dosing was achieved in 100% of technician-assisted deliveries. All patients successfully self-administered microdoses after receiving training. Microdose administration was well tolerated and did not result in any AEs. Conclusion: Microdosing of 0.4 μg of μRx-latanoprost achieved significant IOP reduction. Lower ocular exposure with topical prostaglandin analog microdosing can enable new therapeutic opportunities for optimizing glaucoma treatment. Microdosing may also be beneficial in reducing ocular side effects associated with excessive drug product and preservatives often used to treat chronic ocular diseases such as glaucoma. Keywords: microdosing, piezo-ejection system, latanoprost, IOP, IOP lowering, glaucoma, ocular drug delivery, Optejet, self-administration, usabilit