Quick Hits

FDA displays a kinder, more understanding, side

Agency gives Aerie a chance to prove Rhopressa’s worth; helps Inotek with its phase 3 trial.

By René Luthe, Senior Editor

After approximately 20 years without a new glaucoma drug approved for the U.S. market, two made significant strides toward changing that record over the summer. Further, the FDA’s meetings with the drugs’ makers signaled a willingness to compromise in order to end the long drought in new therapies.

Aerie Pharmaceuticals has reason to celebrate. After it failed the phase 3 trial for its own glaucoma drug, Rhopressa, last spring, the FDA recently agreed that Aerie might change the primary endpoint of its second phase 3 registration trial for the drug, Rocket 2. That endpoint range, now the same range of the phase 3 registration trial results of Rocket 1 that showed success, ranges from above 20 mmHg to below 25 mmHg; previously, the range for the primary endpoint was 20 mmHg to below 27 mmHg. Aerie noted that, in Rocket 1, Rhopressa showed non-inferiority to timolol in that range, “and numerical superiority to timolol at the majority of time points.” Rhopressa is a triple-action eye drop that targets the trabecular meshwork.

An Internet search by Ophthalmology Management revealed only one other occasion on which the FDA agreed to allow a drug maker to change a phase 3 trial’s primary endpoint. “It’s encouraging,” says Douglas Rhee, MD, chair, Department of Ophthalmology and Visual Sciences, University Hospitals Case Medical Center, Cleveland.

Topline results from Rocket 2 are expected later this month; if positive, Aerie says it is on track to file the Rhopressa NDA by mid-2016. Rocket 4, an additional Rhopressa phase 3 registration trial, should begin by year’s end.

The company also announced a “near future” phase 3 trial for its other glaucoma drug, Roclatan. The once-daily drop combines Rhopressa with latanoprost.

Inotek Pharmaceuticals, too, has reason to celebrate. It followed up the release of its phase 2 study data for trabodenoson with a meeting with the FDA in which the agency provided guidance for a phase 3 trial. Phase 2 found that the drug had no waning effect with the extended duration of treatment. For phase 3, the drug must beat placebos; these trials are slated to begin in the fourth quarter. Trabodenoson is a first-in-class selective adenosine mimetic designed to restore the eye’s natural pressure control mechanism.

“Our initial phase 3 trial will be a three-month study with five treatment arms, for a total of approximately 400 patients,” says Claudine Prowse, PhD, vice president, Strategy and Investor Relations Officer. There will be 3 trabodenoson treatment arms, all with doses higher than those administered in the phase 2 monotherapy trial. “We intend to dose up to 2000mcg, and to study both once-daily and twice-daily dosing. There will also be a timolol arm and a placebo arm in the study. The doses were selected to optimize intraocular pressure lowering, while preserving its favorable side-effect profile.”

OCULUS unveils Pentacam AXL

The new device will also include calculation software to eliminate transcription errors.

By Robert Stoneback, Associate Editor

OCULUS released the Pentacam AXL, capable of measuring the anterior eye segment as well as axial length in seconds, the company says. The time required to complete the procedures eliminates the need to relocate the patient, the company reports.

All data measured by the device automatically transfers to IOL calculation software, ruling out manual transcription errors. Data recorded includes the axial length, K values, anterior chamber depth and corneal diameter.

The IOL power calculator includes formulas for normal eyes as well as eyes recovering from refractive surgery. The AXL’s database includes IOLs from many manufacturers.

The AXL is also equipped with Pentacam HR basic software modules, including the fast screening report and the cataract pre-op display.

Eyes can give Ebola a new lease on life

Ocular symptoms can appear weeks after virus is cleared from blood.

By René Luthe, Senior Editor

As the case of an American physician recently made clear, the Ebola virus can live on for weeks in the aqueous humor of survivors — in this instance, 10 weeks after the clearance of viremia. To gain an understanding of the long-term health consequences of Ebola virus disease (EVD), including its effects on the eye, the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, is cosponsoring a study with the Ministry of Health of Liberia: PREVAIL, which began in June, is expected to enroll about 1,500 Ebola survivors in Liberia, plus about 6,000 of their close contacts.

Just when you thought it was over …

Researchers at the recent ARVO meeting presented the case of Ian Crozier, MD, and American infection disease specialist who had joined the international effort against Ebola in Sierra Leone in August 2014. Three weeks later, Dr. Crozier contracted EVD and was evacuated to Emory University Hospital, Atlanta, in critical condition with multiple organ failure. He recovered, but not long after his discharge from the hospital — and nine weeks after EVD had cleared from his blood — Dr. Crozier developed ocular symptoms in his left eye. They included bilateral burning, foreign-body sensation, photophobia and elevated ocular pressure. He was diagnosed with uveitis; a paracentesis of his left anterior chamber revealed Ebola virus RNA in his aqueous humor.

He was treated with prednisone, at first in eye drop form and later, when scleritis and intermediate uveitis on his posterior segment became evident, in oral form.¹ Dr. Crozier’s visual acuity in the affected eye, three months after uveitis set in, recovered to 20/15.

The case adds to findings from the 1995 Ebola outbreak in the Democratic Republic of the Congo, when clinicians reported ocular manifestations in survivors who had been asymptomatic for weeks.

Searching for answers

Back at former Ebola hot-spot Liberia, Elizabeth Bishop, MD, MPH, chief, Consult Services Section at the National Eye Institute, is helping to conduct an eye substudy of PREVAIL.

“We’ve set up a full modern eye clinic at JFK Hospital in Monrovia, with state of the art diagnostic equipment, to try to understand and diagnose the problems Ebola survivors are having,” she says. “It’s very exciting to be able to see changes in the eye that haven’t been able to be characterized before — details of the actual effect of the virus on the retinal layers and so on, which might, hopefully, help us understand how the virus does what it does, which in turn might, hopefully, help us understand more about treatment.” PREVAIL is scheduled to run for five years.

REFERENCE

ASCRS defends iodine, eyedrop practices

Some members report surveyors said, stop this practice.

By Robert Stoneback, Associate Editor

The ASCRS is defending the use the use of diluted povidone-iodine solution for topical infection prophylaxis and the use of multidose topical eye drops on multiple patients, after government surveyors prohibited them.

Both are common presurgical practices by ophthalmologists.

“Some members reported that surveyors have arbitrarily proscribed these well-established and common practices, without any evidence that they pose greater risk,” said David F. Chang, MD, past president and Cataract Clinical Committee member of ASCRS, via press release.

Dr. Chang said no published directive banned the use of the 5% povidone-iodine solution, created by diluting 10% iodine solution (Betadine) with saline solution. However, some ASCRS members have reported that surveyors are questioning or citing its use, along with using eye drops on multiple patients.

Literature strongly supports preoperative povidone-iodine solution use for cataract surgery antisepsis and endophthalmitis prevention, according to the ASCRS’ position statement. The society added that the practice has been used almost universally in ophthalmic surgery for decades, particularly 5% povidone-iodine solution to treat endophthalmitis prophylaxis in the conjunctival sac.

Despite the labeling “do not use in the eye” on containers of 10% povidone solutions, a 5% povidone treatment has been shown to be safe and effective, according to the ASCRS. While the 5% solution is usually prepared by diluting the commercially available 10% iodine solution, 5% povidone-iodine preparations have recently gone to market, but at a significant cost.

Clinical and surgical settings have long recognized that using multidose eye drops on multiple patients is a safe and cost-effective practice, particularly when following safety guidelines for them, including proper disposal techniques, an expiration date of 28 days after initial use and discarding any bottle with suspected tip contamination.

When physicians follow proper protocols, the ASCRS Cataract Clinical Committee strongly supports the use of multidose eye drops on multiple patients.

“The Cataract Clinical Committee is not recommending or suggesting that there is only one best practice,” Dr. Chang said via the press release. “Rather, we want to defend those facilities that choose to use multi-use bottles or dilute 10% Betadine, based on the best medical judgment of their clinical staff.” Comment from the Centers for Medicare and Medicaid Services was not available at press time. OM