Preparing for Presbyopia Pharmacotherapy

Expectations are for a near-term approval, more options to follow, and marked market demand. Cheryl Guttman Krader reports from ASCRS in Las Vegas, USA

Pharmaceutical treatment for presbyopia is on the horizon, and ophthalmologists can anticipate significant patient interest in this topical therapy that offers a solution for those who want to be rid of reading glasses.

“Topical drops for treating presbyopia are a whole new class of therapeutics that will explode over the next few years. Ophthalmologists need to embrace these medications, which look very promising in clinical trials,” said Eric D Donnenfeld MD.

PHARMACEUTICAL APPROACHES Dr Donnenfeld divided the developing medications for treating presbyopia into three categories: miotic-based drops that contain pilocarpine, carbachol, or aceclidine as their active ingredient; combination therapies that include a miotic; and lens restoration drops.

The miotic-based drops increase the depth of focus by reducing pupil size. According to criteria set by the US Food and Drug Administration, gaining market approval will require that these medications demonstrate efficacy for improving near vision by at least three lines without causing any distance vision loss.

“Placing a pinhole at the iris expands the depth of field without impairing the peripheral field, but it can also make the eye more myopic,” Dr Donnenfeld explained.

Among the miotic-based medications in the clinical trial pipeline, AGN-190584 (Allergan) may be the first to market as its New Drug Application is currently under FDA review.

AGN-190584, which contains pilocarpine 1.25%, was investigated in two phase-three studies where it was dosed once daily in both eyes for 30 days. The study results showed the treatment was associated with statistically significant gains in distance-corrected near visual acuity of at least three lines in mesopic conditions without loss of five letters or more in corrected distance visual acuity.

CSF-1 (PresbiDrops, Orasis) is another pilocarpine-based product, but it contains a lower concentration of pilocarpine, 0.4%, and has an oil-based, preservative-free vehicle formulation. Phase two study results comparing CSF-1 with a vehicle showed promising efficacy, safety, and tolerability, and two phase three trials investigating CSF-1 are underway.

MicroLine (Eyenovia), which has also advanced into phase three studies, contains pilocarpine 1% or 2% delivered via a spray jet system (Optejet).

“This proprietary drug delivery system evenly disperses a microdose of 7 μL onto the cornea, and its effect has been reported to last three to four hours,” Dr Donnenfeld said.

Lenz Therapeutics is developing an aceclidine-based drop. In a clinical trial, the medication was associated with maintaining an average pupil size of 2 mm for up to seven hours.

The combination therapy category includes brimochol (Visus), a fixed combination of carbachol and brimonidine. Carbachol is a longer-acting miotic than pilocarpine, and brimonidine has multiple actions able to enhance efficacy and safety.

“Brimonidine prevents pupillary dilation, inhibits ciliary body contraction, and whitens the eyes to prevent ocular redness induced by the miotic. In addition, by reducing aqueous production, brimonidine decreases carbachol turnover and increases its bioavailability,” Dr Donnenfeld explained.

“Phase two trials are about to begin.”

Ocuphire is developing another combination approach using phentolamine (Nyxol) and pilocarpine 0.4%, but the two medications are dosed separately. Phentolamine, an α-1/2 antagonist, is given at night, and pilocarpine in the morning.

“In an initial study, the combination approach showed almost 24 hours of effectivity,” Dr Donnenfeld said.

The lens restoring drop, known as UNR844 (lipoic acid choline ester, Novartis), acts to increase the flexibility of the crystalline lens by oxidizing disulfide bonds. A phase two dose-ranging study of UNR844 is underway.

DEFINING THE PATIENT POOL As an issue estimated to affect more than 2 billion people worldwide, including 123 million Americans, and with consequences that affect quality of life in multiple ways beyond cosmesis, presbyopia is a big problem, Dr Donnenfeld said.

“Glasses, contact lenses, and surgical solutions for presbyopia have important drawbacks. Miotic presbyopia drops are safe, effective, and reversible, which is want patients want,” he said.

Dr Donnenfeld described several groups of “best candidates” for miotic drops. They include emmetropes who are likely uncomfortable with vision correction surgery, hyperopes who will benefit from improvement in near and distance vision, and post-LASIK emmetropes who have already made a significant investment to achieve glasses-free vision.

“Pupil-constricting drops may also help to address high-order aberrations and glare and halo for post-LASIK patients with those issues,” Dr Donnenfeld said.

Pseudophakic patients are another set of candidates. Patients with a monofocal IOL could use presbyopia drops instead of readers. The drops could also be of interest to patients with presbyopia-correcting IOL who want more near vision than their implant provides. Contraindications for miotic drop use include high myopia and a history of retinal tears.

Anticipating high demand for the presbyopia drops, Dr Donnenfeld said, “The volume of patients coming in will stress our offices. Ophthalmology needs to work together with optometry to offer these medications.”

Eric D Donnenfeld MD is a Clinical Professor of Ophthalmology, New York University Medicine, New York, USA. He is a founding partner of Ophthalmic Consultants of Long Island, New York. He is past president of the ASCRS. ericdonnenfeld@gmail.com