SUBSPECIALTY NEWS

Promising Data on Sustained-release Lucentis

A refillable implant rivals injections in efficacy.

BY JERRY HELZNER, SENIOR EDITOR

■ Results of the first clinical study of a sustained-release implant to deliver an approved anti-VEGF drug (ranibizumab) were described as “encouraging” by Roman Rubio, MD, head of ophthalmology at Genentech (South San Francisco, CA). The study found 0.5-mg dosing from a refillable reservoir (ForSight Vision, Menlo Park, CA) produced vision gains comparable to intravitreal injections of the same drug.

“Almost 40% of the 20 patients in the study were able to show three-line gains at 12 months,” said Dr. Rubio. “The average number of refills per patients was 4.8 over 12 months, or a refill every two to three months done in the office. Sustained-release offers the promise of equivalent exposure to monthly doses of the drug without the need for frequent clinic visits or injections.”

Dr. Rubio presented data from the phase 1 proof of concept study last month at the World Ophthalmology Congress in Tokyo. He said results from the study, conducted in Latvia, were positive overall and spurred plans for a larger phase 2 study, which will be conducted at sites in the United States.

“We will be making some improvements in the implantation technique and will also modify some of the implantation tools for the phase 2 study, as the few adverse events we saw were primarily related to implantation of the reservoir,” Dr. Rubio said.

The phase 2 trial may also encompass higher doses of ranibizumab to extend the interval between refills to a target goal of four months. However, like many in the retinal community, Genentech would like to better understand the relationship between anti-VEGF treatment and geographic atrophy (GA) and is currently analyzing data from their own HARBOR to determine whether a relationship is present between the two. Results from the CATT study did associate an increased incidence of GA with more frequent dosing of anti-VEGF drugs.

“The GA question has yet to be answered,” Dr. Rubio said. “The answers will become more clear with further data.”

In contrast to Regeneron (Tarrytown, NY), which has publicly stated that it has little interest in sustained-release formats for its successful drug for retinal disease, aflibercept (Eylea), Dr. Rubio said Genentech has a “group focused on sustained-release ocular delivery.” He said the company is exploring other drug-delivery formats in addition to the ForSight refillable reservoir.

Post-market Issues Consistent With Jetrea Trials

Two ARVO studies track adverse events.

■ Two recent studies, one conducted by an arm of the American Society of Retina Specialists (ASRS), sought to identify the incidence and types of adverse events associated with Jetrea (ocriplasmin, ThromboGenics, Iselin, NJ). The investigators presented their findings at ARVO 2014 in Orlando, FL. The FDA approved Jetrea in 2012 for the treatment of symptomatic vitreomacular adhesion and vitreomacular traction.

One study was conducted by the Therapeutic Surveillance Committee (TSC) of the ASRS. It reviewed adverse event reports for both pre-marketing (999 injections) and post-marketing (4,387 injections) use of ocriplasmin.¹

The study identified eight categories of adverse events. Acute reduction in visual acuity, electroretinogram changes, dyschromatopsia, retinal tears and detachments, lens subluxation or phacodonesis, impaired pupillary reflex, and retinal vessel findings were reported in both the pre- and post-marketing experiences. Ellipsoid zone (inner segment/outer segment) findings were only reported in the post-marketing experience. Rates of post-marketing reports were lower than in the pre-marketing data. Adverse events were transient, and their characteristics were similar between the pre- and post-marketing experience.

The TSC concluded that the post-marketing safety profile following ocriplasmin administration has so far been consistent with the pre-marketing clinical trial program. The TSC urged all practitioners to practice informed management of patient expectations and active post-market surveillance. 

The second study, a Web-based survey conducted by researchers at Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, drew 270 responses covering a total of 1,056 eyes treated with ocriplasmin.²

Respondents identified the following adverse events they had encountered in using Jetrea: acute decline in visual acuity (179 eyes, 17%), development of submacular fluid or serous retinal detachment (108 eyes, 10.2%), dyschromatopsia (96 eyes, 9%), progression of VMT to macular hole (92 eyes, 8.7%), retinal detachment (28 eyes, 2.7%), retinal tear (21 eyes, 2%) afferent pupillary defect (19 eyes, 1.8%), ERG abnormalities (6 eyes, 0.6%), and crystalline lens instability (4 eyes, 0.4%)

The researchers concluded that “although the incidence of many ocular adverse events reported in this study are comparable to those reported in the phase 3 registration trials, additional phase 4 safety studies are warranted to better understand the pathophysiology of ocular adverse events of ocriplasmin.”

REFERENCES

Ohr Plans More Trials for Squalamine Eyedrop

New financing will fund DME studies.

■ Ohr Pharmaceutical, Inc. (Brooklyn, NY), is using proceeds from the sale of common stock to help fund clinical trials of aministerol squalamine in eyedrop form for the treatment of retinal disease.

Ohr CEO Irach Taraporewala, PhD, said the company expects to complete enrollment in the OHR-002 wet AMD squalamine study and initiate two randomized, controlled, investigator-sponsored trials to evaluate squalamine eyedrops for DME this quarter.

The OHR-005 study will evaluate squalamine eyedrops in a randomized, masked, placebo-controlled trial of approximately 30 patients with DME. The OHR-006 study will evaluate squalamine eyedrops in combination with monthly intravitreal ranibizumab injections for DME patients who have been substandard responders to monthly ranibizumab injections. The trial will enroll approximately 20 patients and will be randomized, masked, and placebo-controlled.

Interim data from the OHR-002 study of squalamine are expected to appear in the second quarter of this year, with final data on the study available in the first quarter of 2015.

Ohr sold 1.8 million shares of common stock to private investors at $10 per share, for gross proceeds of approximately $18 million. Ohr said it intends to use the proceeds for research and development, general and administrative expenses, manufacturing, and potential acquisitions of companies and/or technologies that complement its business, in addition to the aministerol squalamine eyedrop trial.

“We continue to execute our strategy of developing an ophthalmology-focused pipeline with greater financial strength,” Dr. Taraporewala said. “This financing provides us with the necessary resources to continue our clinical development programs and seek out additional innovative ophthalmic candidates.”