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.
■ PanOptica funded for wet AMD eyedrop trials. PanOptica, Inc., Bernardsville, NJ, has raised up to $45 million in Series B financing to fund the clinical trials for its lead compound, PAN-90806, a small-molecule selective inhibitor of VEGF signaling that is undergoing study as a topical treatment for wet AMD.
New participant Novo Ventures and existing investor Third Rock Ventures co-led this round of financing, which also included founding investor SV Life Sciences
PanOptica also announced it has dosed the first patient in its phase 1 clinical trial for PAN-90806 less than one month after the company received FDA clearance for its investigational new drug application. The phase 1 trial is a two-month, open-label study involving approximately 30 patients at 15 to 20 clinical sites around the United States.
The trial goal is to assess the safety and tolerability of topical ocular PAN-90806 at three dosage strengths in patients with active, subfoveal choroidal neovascularization associated with neovascular AMD. PanOptica expects to report trial data by year-end.
■ Endophthalmitis after intravitreal injection. Researchers led by Nadim Rayess, MD, of Wills Eye Institute, Philadelphia, PA, presented findings from a retrospective, multicenter study to determine if rates of endophthalmitis infections following intravitreal injection varied with type of retinal disease treated. The researchers reviewed 308,113 injections for wet AMD, DME/PDR, and RVO.
They identified 133 cases of endophthalmitis in the study. However, they found no statistically significant differences in infection rates among the three disease types. They presented their findings at ARVO 2014.
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.”
1. Hahn P, Chung MM, Flynn HW Jr, et al. Safety profile of ocriplasmin for symptomatic vitreomacular adhesion — a comprehensive analysis of pre- and post-marketing experiences. Invest Ophthalmol Vis Sci. 2014;55:ARVO E-Abstract 2209.
2. Shah SP, Jeng K, Fine HF, Wheatley HM, Roth DB. Postmarketing surveillance survey of adverse events of ocriplasmin (Jetrea). Invest Ophthalmol Vis Sci. 2014;55:ARVO E-Abstract 2208.
■ Sirolimus shows promise in posterior uveitis. Santen, Inc., Emeryville, CA, said the phase 3 SAKURA study evaluating intravitreal injections of sirolimus in patients with noninfectious posterior-segment uveitis (NI-PSU), met its primary endpoint.
“We believe sirolimus may provide physicians with the first nonsteroidal intravitreal treatment option for their patients suffering with NI-PSU,” said Naveed Shams, MD, PhD, chief scientific officer and CEO of Santen.
SAKURA is an ongoing multinational, multicenter, randomized study encompassing 347 patients with noninfectious posterior, intermediate, or panuveitis at approximately 150 sites. Eligible patients were randomized into three treatment arms, each receiving different doses of sirolimus. The primary endpoint is the proportion of patients achieving a vitreous haze score of 0 in the fifth month. A second phase 3 SAKURA study using the same protocol is enrolling patients.
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.”
■ Avalanche gets major funding for gene therapy. Avalanche Biotechnologies, Inc. (Menlo Park, CA), a developer of innovative gene therapies for serious eye diseases such as wet AMD, has completed a $55 million Series B financing.
Proceeds from this financing round will be used to advance the company’s clinical programs in retinal disorders, including Avalanche’s lead product, AVA-101, for wet AMD. In addition, the company will invest in manufacturing and clinical infrastructure for the lead program and accelerate the development of pipeline programs based on Avalanche’s proprietary research platform.
Avalanche has stated that gene therapy has the potential of making wet AMD curable rather than remaining a chronic disease that requires ongoing management.
■ Neurotech names Oswald CEO. Neurotech Pharmaceuticals, Inc. (Cumberland, RI) has appointed Quinton Oswald CEO, replacing Edward “Ted” Danse. Mr. Oswald is the former CEO of SARcode Bioscience, Inc., which Shire acquired in 2013.
Mr. Oswald’s expertise in bringing wet AMD treatments through clinical trials and into commercial launch was cited by Neurotech executive chairman James Mazzo as a key factor in his hire.
Neurotech is pursuing treatments for both wet and dry AMD. Mr. Oswald oversaw the successful launch of Lucentis (ranibizumab) for Genentech almost a decade ago.
■ Patients receive Argus II retinal prosthesis. Second Sight Medical Products, Inc. (Sylmar, CA), said its Argus II Retinal Prosthesis System is being implanted in patients with retinitis pigmentosa in the United States for the first time since the FDA approved it last year. The company did not reveal the number of patients receiving the Argus II implant.
The first commercial implants were performed at the University of Michigan’s Kellogg Eye Center by Thiran Jayasundera, MD, FRCSC, and David N. Zacks, MD, PhD. Ultimate outcomes will not be known until the patients go through a period of rehabilitation ito train them to use the device.
■ ODs win more privileges. Despite opposition from the Tennessee Academy of Ophthalmology and the Tennessee Medical Association, optometrists there secured legislation, signed into law in April, that allows ODs to inject local anesthesia for six types of lid procedures. RP