August 2010

 

OPHTHALMOLOGY NEWS

 

Checking in with CF101


by Vanessa Caceres EyeWorld Contributing Editor

   

Oral anti-inflammatory pill may one day treat dry eye

Ophthalmologists often lament the lack of options when it comes to treating dry-eye patients.

Now, an oral drug undergoing tests for rheumatoid arthritis patients may provide some relief.

CF101 (Can-Fite BioPharma, Petach Tikva, Israel) is an oral A3 adenosine receptor agonist that has been tested in Phase II studies as an anti-inflammatory agent for various rheumatic conditions. During studies for CF101's use in rheumatoid arthritis, patients who had concurrent dry eye reported that they were using their artificial tears less often, said Pnina Fishman, Ph.D., co-founder, Can-Fite BioPharma. This spurred the company to investigate the drug's further potential for ocular inflammation.

Investigators, including lead author Isaac Avni, M.D., Can-Fite BioPharma, and Dr. Fishman reported their Phase II trial results in dry-eye patients in an article published online in March in Ophthalmology.

Study details

The randomized, multicenter, placebo-controlled trial focused on the safety and efficacy of CF101 taken daily in patients with moderate to severe dry eye. Sixty-eight patients eventually completed the study, which took place over a four-week screening period, a 12-week treatment period, and a two-week follow-up. There were 35 patients in the placebo group and 33 patients in the treatment group who completed the study from an original pool of 80 patients total. More than half of the patients in both groups were female.

Patients were 18 or older and had to be diagnosed with at least one ocular symptom associated with dry eye (such as photophobia, blurred vision, or dryness), a Schirmer's tear test 1 result without anesthesia and less than 7 mm/5 minutes in either eye, and positive fluorescein staining results. There were a number of exclusion factors in the study, including a history of Sjgren's syndrome, Stevens-Johnson syndrome, cyclosporine use within 3 months before the screening visit, and the use of other disease-modifying drugs.

Patients received the medication or a placebo twice daily; they were also provided with artificial tears that they could use up to eight times a day. The study's primary endpoint was a tear film breakup time improvement of 25% or more over baseline at week 12. Alternately, an improvement of 25% or more in superficial punctuate keratitis over baseline at week 12 as measured by fluorescein staining or a Schirmer's test were also considered a success. Investigators also measured the tear meniscus at week 12 for the target eye and obtained a dry-eye symptom score based on patient answers to a questionnaire.

The study's safety measurements focused on adverse events and their relationship to the study medication, as well as safety as measured by physical examinations, slitlamp examinations, and other evaluations.

Of the group treated with CF101, 84.6% of patients had more than a 25% improvement in their corneal staining compared with 52.2% of the patients with a similar improvement in the placebo group. Investigators also tracked a progressive improvement from the baseline of the corneal staining and the clearing of corneal staining in the treatment group versus placebo throughout the study period. The difference was particularly marked at week 12. Tear meniscus was also better in the treated group.

Both groups had an improvement in the mean change of tear film breakup time compared with baseline, but the difference was more noticeable in the CF101-treated group. Investigators did not find any difference in Schirmer's test or questionnaire results.

Although the study had no serious adverse events, two patients experienced myalgias and recurrent corneal erosions, which led them to discontinue treatment. "The most frequent reported adverse events included constipation, headache, palpitations, itching, abdominal pain, arthralgia, myalgia, fatigue, and dry mouth," investigators wrote. The drug's safety is also supported by clinical trials in other specialties with a total of more than 500 patients, Dr. Fishman said.

No changes in vital signs were observed, but interestingly, at week 12, the treatment group had a 1.1 mmHg decrease in IOP compared with baseline, which was statistically significant compared with placebo. This finding prompted the design of a Phase II trial to evaluate CF101 use in patients with elevated IOP, Dr. Fishman said. Trial details are available on ClinicalTrials.gov, but the website says that the trial is not yet recruiting patients.

Two weeks after treatment ended, changes to corneal staining that had occurred during use of CF101 had stopped, investigators reported.

Weighing in

Dry-eye specialists report that the number of treated study participants was small and that it is notable that most of the investigators are Can-Fite employees. Even so, they are interested in learning more about CF101.

"It's exciting that this is an oral anti-inflammatory medication," said Robert Latkany, M.D., founder and director, Dry Eye Clinic, New York Eye and Ear Infirmary, New York. "There are not a lot of oral medications for ocular surface disease beyond tetracycline, fish oil, and steroids."

The drug's pill form could help with patient compliance, Dr. Fishman said. However, she added that the company may one day make it in a topical form.

"This offers another potential treatment in the management of dry eye. However, additional studies are required," said Eric D. Donnenfeld, M.D., co-chairman, Cornea, Nassau University Medical Center, East Meadow, N.Y. Dr. Donnenfeld said A3 adenosine receptors have been associated with cardiac and neutrophil degranulation; oral medications are more likely to have systemic side effects, he added.

Andrew Huang, M.D., professor of ophthalmology, Washington University, St. Louis, believes CF101 could have a role in dry-eye therapy but questions whether all dry-eye patients require anti-inflammatory treatment. He also wonders if patients would need to take a drug like CF101 chronically, considering that some of its effects wore off within two weeks after treatment stopped. He would like to see a medication that can help stop dry eye in the long run versus one that just relieves signs and symptoms.

Whether it's CF101 or another drug under investigation, such as Prolacria 2% (diquafosol tetrasodium ophthalmic solution, Allergan and Inspire Pharmaceuticals, Durham, N.C.) or SAR 118 topical ophthalmic solution (SARcode Corporation, San Francisco), Dr. Latkany believes another option will be available in the near future. "Millions of people are suffering, but there are only a handful of options," he said. "I'm interested in all of these."

Editors' note: Dr. Fishman is a founder of Can-Fite BioPharma (Petach Tikva, Israel). Dr. Latkany has financial interests with Alcon (Fort Worth, Texas) and Allergan (Irvine, Calif.). Dr. Donnenfeld has financial interests with Alcon, Allergan, and Bausch & Lomb (Rochester, N.Y.), among other ophthalmic companies. Dr. Huang has no financial interests related to his comments.

Contact information

Donnenfeld: 516-446-3525, eddoph@aol.com
Fishman: pnina@canfite.co.il
Huang: 314-362-0403, huanga@vision.wustl.edu
Latkany: 212-689-2020, relief@dryeyedoctor.com

Checking in with CF101 Checking in with CF101
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