Rhopressa wins confidence of FDA advisory panel

Clinical trials are convincing of the drug’s ability to lower IOP.

By René Luthe, senior editor

Clinical trials for Aerie’s netarsudil ophthalmic solution 0.02% (Rhopressa) support its efficacy for reducing elevated IOP in patients with open-angle glaucoma or ocular hypertension, according to a unanimous vote of the FDA’s Dermatologic and Ophthalmic Drugs Advisory committee.

“Hopefully, it will lead to the first FDA approval of a new class of intraocular pressure lowering-medications since 1996,” says Nathan Radcliffe, MD, glaucoma surgeon and clinical assistant professor, New York Eye and Ear Infirmary.

The clinical trials that the advisory committee reviewed were results from the series of Rhopressa trials dubbed Rocket (Rocket 1, Rocket 2, the 90-day efficacy results from Rocket 4), and the first trial from the series called Mercury, the initial Phase 3 registration trial for Aerie drug candidate Roclatan (netarsudil/latanoprost ophthalmic solution) 0.02%/0.005%. (Roclatan’s new drug application is expected to be filed with the agency by June 2018. In two of the Mercury trials, Roclatan achieved safety, efficacy and primary efficacy endpoint goals, according to Aerie.)

Dr. Radcliffe explains how Rhopressa, administered once daily, works: “A rho kinase inhibitor, netarsudil lowers intraocular pressure through several mechanisms, one of which is to facilitate the outflow of aqueous humor through the trabecular meshwork, the eye’s natural outflow pathway.”

Preclinical and clinical studies have also demonstrated that netarsudil lowers episcleral venous pressure, according to Aerie.

The review with the FDA panel also included discussion on the draft product labeling that the FDA has proposed, according to Aerie.

On a second key issue, the committee considered whether the clinical trials demonstrate that the novel eye drop’s efficacy outweighs the safety risks identified with it. The Advisory Committee voted nine to one in favor.

Feb. 28, 2018 is the goal date for the FDA to take action, under the Prescription Drug User Fee Act. While the FDA is not bound to act by the advisory committee’s guidance, it normally does: a McKinsey Center for Government 2013 report showed that the agency’s approvals or denials were “broadly consistent” with the committee’s opinions on NDAs and biologic license applications. OM

Disclosure: Dr. Radcliffe has financial interests with Aerie Pharmaceuticals.

Communities find diabetes screenings do help

Physicians are also examining whether eyedrops have a future in DME treatment

By Robert Stoneback, associate editor

The NEI estimates that 7.7 million Americans have DR, of which about 750,000 also have DME. November is National Diabetes month, so we are bringing you information about communities trying to find and treat diabetic patients — and a possible alternative to anti-VEGF injections.

GREATER ACCESS TO SCREENINGS

For the past several years, primary-care clinics in California’s Los Angeles County have been photographing diabetics’ eyes to help speed up their rate of initial screenings, says a June 12 article in the Los Angeles Times. Four years ago, most diabetics in the county system — the largest in the United States, at more than 800,000 patients a year — weren’t getting screened for DR. Now, the fundus photographs are sent to ophthalmologists, so patients who show signs of DR can schedule a screening. The system has cut the wait time for initial screenings by 89%.

Lauren Daskivich, MD, told the LA Times screening rates in the county have improved about 65%. In March, Dr. Daskivich published in JAMA, showing screening rates increased from 41% to 57% when medical assistants began taking photos of diabetic patients’ eyes.

Research published this July in the BMJ shows similar results. As reported in late July by the BBC, the study conducted by the U.K.’s Swansea University found the rate of severe sight impairment in Welsh citizens dropped from 31.3 people per 100,000 to 15.8 people per 100,000 between 2007 and 2015. This decrease occurred despite 52,229 new diabetes diagnoses in Wales during the same period.

U.K. health experts, say the BBC, credit the drop with annual national retinopathy screenings offered to diabetics age 12 or older. The screenings began in Wales in 2007.

TELE-OPHTHALMOLOGY UNIT

New York City’s Presbyterian/Columbia University Medical Center has also started a new initiative to make eye screenings more widely available. This fall, CUMC unveiled a state-of-the-art mobile eye disease testing center. According to the hospital, this tele-ophthalmology unit is the first of its kind in the country and targets sight-threatening conditions such as diabetic retinopathy, macular degeneration, glaucoma and cataracts.

In a press release, CUMC associate professor of ophthalmology, Lama Al-Aswad, MD, MPH, said the unit was especially important to help reach people in underserved communities, who typically don’t have access to proper eye care.

According to the university, the tele-ophthalmology unit is equipped with an array of diagnostic equipment, including a Wi-Fi data transmitter that allows clinicians at CUMC to help evaluate patient data in real-time. Additional instructions or referrals can also be distributed to patients at the tele-ophthalmology unit.

The tele-ophthalmology unit is expected to perform nearly 2,000 free screenings a year in New York City neighborhoods, such as the Bronx, Washington Heights and Harlem. As of the start of autumn, it had screened about 160 individuals in the city.

DROPS FOR DME

Two companies, Verseon and SciFluor Life Sciences, are studying the use of topical eyedrops to treat DME patients. SciFluor has announced positive results of a phase 1/2 study of its in-development topical treatment, SF0166. The primary safety outcome was met over the 56-day trial length, divided between treatment course and follow-up period. Of the 40 patients in the study, more than half demonstrated a retinal thickness reduction and improved visual acuity. SF0166 showed biological activity in each treatment dosage, 2.5% and 5%, the company says. More study details can be seen at www.clinicaltrials.gov, and searching for ID#NCT02914613.

Verseon presented efficacy results for its plasma kallikrein inhibitor medication at the 2017 BIO International Conference in San Diego this past June. Verseon says plasma kallikrein levels and activity are upregulated into the eyes of DME patients, triggering inflammatory pathways and vasodilation of the retina, causing edema. Verseon’s data suggest that its drops can slow DME progression. The use of eyedrops would help avoid the side effects typically associated with injection and laser-based DME treatment such as inflammation, infections and cataracts, it says.

A 2016 study, published in Seminars in Ophthalmology, found plasma kallikrein was effective in decreasing retinal vascular permeability in diabetic animals (visit tinyurl.com/y6wob7m9 ).

Verseon and SciFluor haven’t been the only entities interested in whether eyedrops would be an effective method of administration for diabetic retinopathy treatment.

A check at clinicaltrials.gov found a good handful of universities, hospitals and pharma houses, around the world, have tried as well. Virtually all, however, are listed as completed with no results listed.

Jorge I. Calzada, MD, FACS, president, Charles Retina Institute in Memphis, Tenn., says that while topical therapy for DR and similar diseases “would be wonderful,” there remain technical challenges in achieving a significant and useful clinical response with eyedrops in these conditions.

“I will remain skeptical until I see large phase 3 clinical data,” says Dr. Calzada. OM