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Dry-Eye Phase III Trial Enrolled, OphthaliX 'Wets' Oral Appetite

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By Randy Osborne
Staff Writer

Dry-eye syndrome (DES) was not the first indication that OphthaliX Inc. planned to tackle with its first-in-class A3 adenosine receptor agonist CF101, though a 24-week, 236-patient, placebo-controlled Phase III trial is already enrolled, from which data are expected to spill out by the fourth quarter of this year.

"Serendipity data" provided anecdotally by patients in a rheumatoid arthritis (RA) trial with CF101 led to the DES experiments, said Pnina Fishman, CEO of Can-Fite BioPharma Ltd. "They approached the investigators and claimed that they did not need to use eye drops anymore," she told BioWorld Today.

In December 2011, Can-Fite, of Petach Tikvah, Israel, changed the name of its subsidiary Denali Concrete Management Inc. to OphthaliX. A month earlier, Can-Fite had acquired 82 percent of the firm's U.S. stock market shell and transferred CF101 to OphthaliX.

DES was chosen for study "not because it's an easy indication or a tough indication," Fishman said. "We just saw the data and decided to go on with it." Patients are randomized to receive two oral doses of CF101 and a placebo.

A Phase IIb study goes on in RA, "which we are going to conclude quite shortly. Toward the end of this year, we will be able to know if both RA and dry-eye syndrome can be treated by CF101," she said.

Symptoms of DES vary, and can include dryness, foreign body sensation, itching, burning sensation, eye pain and sensitivity to light. Advanced cases may lead to damage on the ocular surface and decreased vision. The only approved drug for the condition is Irvine, Calif.-based Allergan Inc.'s Restasis (0.05 percent cyclosporine solution), which is only cleared for marketing in the U.S., noted Barak Singer, CEO of OphthaliX.

Importantly, CF101 is given orally, twice per day (morning and evening), he said – something very unique in the field of ophthalmic drugs," and a factor that should help with compliance over eye drops, Singer told BioWorld Today. "If our mechanism works and proves itself in a large-scale study, we can deal with the cause of the disease and not only help [patients] feel a bit better in the eye," he added.

Fishman said another drawback to Restasis is a painful sensation reported by some patients when they give themselves the drops. "It may help to some extent in fixing the dry-eye situation," she said. "At the same time, it burns the eye when it is administered."

OphthaliX "may go down the road also to topical treatment," she said, but this would be complementary to the oral drug, with its better compliance and proven safety, having been given to more than 1,000 patients without any significant problems.

"Our technology is based on scientific findings showing that the drug will bind only to the pathological cells," Fishman said. "It will not bind to the normal cells because they have very little or no expressions of this receptor. We're talking about a targeted therapy."

The current Phase III trial will not be enough for approval. "We will have to go for an additional Phase III study in order to register, and it will be more or less the same size," she said. This study would begin as soon as the current one finishes, assuming positive results. Phase II data were published in the journal Opththalmology.

Candidates crowd the DES field. In January, Brisbane, Calif.-based SARcode Bioscience Inc. enrolled its first subject in a second pivotal Phase III trial, called OPUS-2, with 5 percent lifitegrast ophthalmic solution.

Lifitegrast, a small-molecule integrin antagonist, was chosen from more than 1,000 synthesized molecules for its ability to block the lymphocyte function-associated antigen-1/intercellular adhesion molecule interaction, the company said.

The OPUS-2 study includes 21 sites across the U.S., and will enroll about 700 subjects who have used artificial tears in the past month. Lifitegrast or placebo will dosed two times per day for 12 weeks. The two primary endpoints are mean change from baseline in inferior corneal staining score and the mean eye-dryness score, both measured at 12 weeks.

Acucela Inc., of Seattle, has 2 percent rebamipide ophthalmic suspension in Phase III trials, too. The compound was launched at the start of 2012 in Japan as Mucosta by Tokyo-based Otsuka Pharmaceutical Co. Ltd., which discovered repamipide. Rebamipide works by increasing mucin in the tear film covering the conjunctiva and cornea. (See BioWorld Today, July 12, 2012.)

RegenerRx Biopharmaceuticals Inc., of Rockville, Md., has RGN-259 (T-beta4 preservative-free eye drops) at the Phase II stage for DES in graft-vs.-host disease. The company also tried RGN-259 in a Phase II study with diabetic patients who underwent corneal epithelial debridement during vitrectomy surgery. Slow enrollment and new data generated under a compassionate-use investigational new drug application led to the closure of the trial in January 2009.

Cambridge, Mass.-based Eleven Biotherapeutics Inc. in December 2012 started a Phase Ib trial to test EBI-005, its lead ophthalmic protein product, in patients with DES. The study, which will enroll up to 80 subjects and will determine safety as the primary endpoint, is expected to complete in the first half of this year. EBI-005 is described by the company as a rationally designed topical protein designed to inhibit the interleukin-1 receptor.

Ophthalix's stock (OTCBB:OPLI) closed at $1.25, unchanged, on March 12, its most recent day of trading.