Acucela Inc., of Seattle, began a Phase III trial of 2 percent rebamipide ophthalmic suspension for dry eye syndrome. The trial will support eventual U.S. regulatory submission for the product, already launched in Japan as Mucosta by Otsuka Pharmaceutical Co. Ltd.

The FDA requires a clinical study to be carried out with a U.S. patient population, according to Acucela President and CEO Ryo Kubota.

"We were able to garner some good information from the Phase II studies, and the successful Japanese studies, which led to approval of rebamipide ophthalmic solution for the treatment of dry eye under the trade name of Mucosta in Japan, to inform our Phase III program/trial design," Kubota told BioWorld Today.

The randomized, placebo-controlled, double-masked trial will enroll 560 subjects in two treatment groups, with completion anticipated by the end of 2013.

Dry eye disease is one of the most common diseases seen by ophthalmologists, affecting 25 million Americans and 370 million people worldwide.

Dry eye is a disease of the tears and ocular surface. It is characterized by sensations of dryness, foreign body, itching burning, pain and photophobia, and it can lead to damage to the eye and complications.

Otsuka chose Acucela as its U.S. partner on the basis of its experience in the ophthalmology field. The two companies partnered on Sept. 4, 2008, to co-develop rebamipide ophthalmic suspension for treatment of dry eye syndrome in the U.S. (See BioWorld Today, Sept. 8, 2008.)

Under the agreement, the parties will collaborate in clinical development efforts, with Acucela spearheading the U.S. regulatory strategy. Upon FDA approval, the parties may negotiate the terms under which Acucela may co-promote the drug with Otsuka in the U.S.

Acucela received an up-front payment and is eligible to receive milestone payments and a royalty on sales. Otsuka will pay all clinical development and commercialization expenses.

Acucela's pipeline includes two other compounds in development for visual maladies.

Its candidate ACU-4429, a small-molecule visual cycle modulator, produced positive results in a Phase I study. Data from the trial, which were published in Retina: The Journal of Retinal and Vitreous Diseases, showed a well-tolerated, dose-dependent modulation of the visual cycle through electroretinography.

Phase II results, reported in May, showed the drug produced a dose-dependent response and modulated rod visual cycle, as measured by electroretinogram, for doses up to 10 mg. That study was designed to evaluate the effect of ACU-4429 on rod function in patients with advanced, dry age-related macular degeneration/geographic atrophy.

The firm also began a Phase I/II trial of OPA-6566 in partnership with Otsuka in late 2011. OPA-6566 is an adenosine A2 receptor agonist in development as an ophthalmic solution to reduce intraocular pressure in open-angle glaucoma or ocular hypertension.

A 2010 deal gives Acucela an opt-in right to co-develop and co-promote the compound in the U.S. in exchange for early clinical development work.

Acucela has some competition in the dry eye arena.

RegeneRx Biopharmaceuticals Inc. recently reported preliminary Phase II results showing that RGN-259 (Tbeta4 preservative-free eye drops) in severe dry eye was found to be safe and well tolerated and met key efficacy objectives with statistically significant sign and symptom improvements, compared to vehicle control at 28 days post-treatment.

Eleven Biotherapeutics Inc. is preparing to enter the clinic this year with an interleukin-1 inhibitor for dry eye. It presented data at the Association for Research in Vision and Ophthalmology meeting in 2010 showing that the drug, EBI-005, has high potency, thermal stability and very low systemic exposure.

OphthaliX Inc. is developing its A3 adenosine receptor agonist for dry eye, CF101 . Preclinical studies showed the drug was efficacious in anterior uveitis, and it is in ongoing studies in dry eye.

SARcode Bioscience Inc. is conducting a pivotal Phase III trial of its drug, SAR118 ophthalmic solution in dry eye. The trial will measure safety and efficacy of the drug compared to placebo over 12 weeks, with a primary endpoint of corneal florescein staining score and vision-related function score as measured by ocular surface disease index.

Acucela's Kubota has made it a goal to educate people worldwide about eye diseases, and began actively blogging and tweeting two years ago to increase awareness of eye problems.

"In line with Acucela's corporate strategy, the company is committed to developing ophthalmic products where there exists an unmet or underserved medical need and, furthermore, developing products that get to the root cause of the disease vs. providing an incremental improvement," Kubota said.

"Patients suffer tremendously with dry eye, impacting quality of life," he added.