Therapeutics

Ocular therapies on the horizon

Physicians await novel treatments for dry eye, keratoconus, and conjunctivitis.

BY VANESSA CACERES, CONTRIBUTING EDITOR

Ophthalmologists looking for a wider range of ocular therapies to treat common ophthalmic problems may soon have more treatment options available.

Here’s a look at dry eye, keratoconus, and conjunctivitis treatments currently in clinical trials that may soon receive U.S. FDA approval.

Dry eye treatments

The need for more expansive dry eye therapies is critical as ophthalmologists continue to treat a wider range of patients with the condition, says William Trattler, MD, Center for Excellence in Eye Care, Miami.

“The incidence of dry eye is underappreciated even though it’s so common,” he says. “It’s worsened by age and by the use of computers and smartphones.”

Offering just artificial tears doesn’t truly help patients, says Dr. Trattler, who likens this treatment method to offering pain relief medication without searching for the cause of the actual pain. Ophthalmologists want — and need — more medications to address dry eye causes.

“There are several potential therapeutic agents for dry eye in various stages of development,” says Kendall E. Donaldson, MD, associate professor of clinical ophthalmology, Bascom Palmer Eye Institute, University of Miami.

Lifitegrast (Shire Pharmaceuticals), the closest to FDA approval, showed great promise in clinical trials, Dr. Donaldson says. This medication completed phase 3 FDA trials and awaits FDA approval, says Eric D. Donnenfeld, MD, clinical professor of ophthalmology, New York University Medical Center, New York. Lifitegrast ophthalmic solution is a first-in-class small molecule immunomodulator that targets T-cell mediated chronic inflammation and blocks the binding of two proteins that mediate the dry eye-associated inflammatory cascade, he says. “The compound has several different points of activity and rapid onset of action.”

Shire submitted a New Drug Application for Lifitegrast earlier this year. The FDA granted a priority review and is expected to make a decision regarding Lifitegrast by Oct. 25.

Another drug, KPI-121 (Kala Pharmaceuticals), will be a welcome addition to dry eye and ocular surface treatment, Dr. Donnenfeld says. KPI-121, a nanotechnology form of loteprednol etabonate, improves drug penetration and retention in mucosal tissues. “It rapidly penetrates the mucosal barrier and then spreads a coating layer of the drug on the ocular surface,” Dr. Donnenfeld says. “The medication has been tested in the treatment of dry eye disease and shows a rapid resolution of signs and symptoms.”

The nanoparticle formulation has been studied in clinical trials for ocular pain, inflammation, dry eye, and meibomian gland disease. KPI-121 had positive phase 2 results announced in April.

In addition, MIM-D3 (Mimetogen) uses a dual mechanism of action against dry eye and could be an intriguing addition to the current dry eye treatments available, Dr. Donnenfeld says. The medication, which is a small-molecule tyrosine kinase receptor agonist, is currently in phase 3 trials. Other pipeline drugs for dry eye include OTX-DP (Ocular Therapeutix), a sustained release dexamethasone, and RU-101 (R-Tech Ueno), a recombinant human serum albumin, Dr. Donaldson says.

Corneal crosslinking

Ophthalmologists familiar with corneal collagen crosslinking are eager to use the treatment in the United States with keratoconus patients, Dr. Trattler says.

“Once approved, patients with keratoconus should be counseled for treatment as soon as they can,” Dr. Trattler said. “It’s something that we’ll use all the time. Patients, especially younger ones, should get early treatment rather than waiting until keratoconus is too advanced.”

“Ophthalmologists strongly support the use of collagen crosslinking based on the results in several other countries as well as extensive off-label use and use within trials in the United States,” Dr. Donaldson adds.

Avedro’s riboflavin ophthalmic solution/KXL System for corneal crosslinking can help to stabilize corneal thinning and steepening associated with keratoconus and ectasia.

“Crosslinking causes a flattening and strengthening effect that has been associated with an improvement in uncorrected visual acuity,” Dr. Donaldson says.

According to research from the Eye Bank of America, corneal crosslinking could reduce the number of corneal transplants performed for these conditions by 40%.

Avedro received a response letter from the FDA regarding its riboflavin ophthalmic solution/KXL System, which identified areas of the application concerning the device requiring additional information. These areas did not pertain to the clinical study safety or efficacy data. “The primary issue was that the three prospective, randomized, 12-month trials were performed with a different device than that proposed for FDA approval,” Dr. Donaldson said.

New trials were requested using the proposed device and standardized amounts of riboflavin and ultraviolet light. Crosslinking is currently undergoing phase 3 trials in the United States.

Conjunctivitis

In August, Shire acquired Foresight Therapeutics, makers of FST-100. The medication is a topical ophthalmic drop that combines 0.1% dexamethasone, a steroid, and 0.6% povidone iodine, which is used as an off-label treatment for the disease. FST-100 is in late stages of development to treat viral and bacterial conjunctivitis.

“The steroid in this medication will help treat inflammation, which is common with infections,” Dr. Trattler says. “It’s a novel combination drug, and there have been studies for it around the world with promising results.”

Shire will handle phase 3 trials for the medication, according to a company press release. OP