Take-home message: The efficacy of a novel dry eye therapeutic may bring a valuable addition to the dry eye armamentarium with a rapid onset of action and better patient tolerability.
Elk Grove, CA—A newly developed drug for treating dry eye (OTX-101; Seciera, Auven Therapeutics) seems to be a potential beneficial therapy based on the results of a phase IIb/III clinical trial in which the safety and efficacy of the formulation were evaluated.
Results showed that the two concentrations of the drug were well tolerated and patients had improved tear production and less inflammation by 12 weeks. The future introduction of a new dry eye formulation would be a welcome addition considering the high frequency with which dry eye occurs, according to Joseph Martel, MD.
Up to 40% of all visits to ophthalmologists are scheduled because patients are seeking help for dry eye symptoms, he noted.
“Ten to 15 million patients in the United States have dry eye and Sjorgen’s syndrome, the latter of which is associated with dry eye, dry mouth, and inflamed joints, and develops in 1% of the population,” said Dr. Martel, director, Department of Ophthalmology, California Northstate College of Medicine, Elk Grove, CA. “Dry eye is a painful, debilitating disease.”
A number of dry eye therapies have become commercially available recently. However, many of the dry eye drops are palliative and do not address the disease. The efficacy with cyclosporine ophthalmic emulsion 0.05% (Restasis, Allergan) helps some, but many patients cannot tolerate it due to burning and irritation upon instillation, which reduces patient compliance, he summarized.
Currently, this suggested there is a large number of a patient without effective treatment.
The manufacturer describes OTX-101 as a novel patented nanomicellar formulation of unpreserved cyclosporine that in animal studies of New Zealand rabbits exhibited superior ocular tolerability to that of cyclosporine A. In that study, the tissue distribution of the drug in the cornea and superior bulbar conjunctiva was greater when compared with that of cyclosporine A.
Phase IIb/III findings
The trial had a multicenter, double-masked, parallel group design with three treatment arms: vehicle (n = 152) and two doses of the cyclosporine nanomicellar solution, 0.05% and 0.09% (n = 151 and n = 152, respectively).
After a 2-week vehicle run-in period, patients were treated for 12 weeks. Patients were not permitted to use artificial tears during the study, which was conducted at 29 sites in the United States.
Primary efficacy endpoints were conjunctival staining and the SANDE (Symptom Assessment iN Dry Eye) score. Secondary efficacy endpoints were corneal staining, tear film break-up time, and Schirmer’s test results. Of the patients enrolled, 426 completed the study, in the three groups, 144, 142, and 140, respectively.
Investigators reported that both drug concentrations were superior to the vehicle at all time points when analyzing the changes in conjunctival staining from baseline (0.05% concentration, p = 0.006; and 0.09% concentration, p = 0.008, compared with the vehicle).
Both concentrations also were superior to the vehicle in total and inferior corneal fluorescein staining at the final evaluation. Tear production was superior with both concentrations of the active treatment compared with the vehicle. The 0.09% drug concentration was significantly (p = 0.007) better compared with the vehicle and resulted in 17.9% of patients having a 10-mm or greater improvement on Schirmer’s testing compared with 7.6% of patients assigned to the vehicle.
Regarding the SANDE score, the three study arms showed an approximate 30% improvement in symptoms over the study course.
The agent seemed to perform well in the central cornea, which is the area that the FDA considers to have the greatest clinical relevance, Dr. Martel noted.
In contrast, the OPUS-1 study of lifitegrast (Shire Pharmaceuticals) showed that compared with placebo, lifitegrast did not differ significantly from that of placebo in central corneal staining but did differ significantly inferiorly and superiorly. The OPUS-2 and -3 studies of the drug did not show a trend toward significance in inferior corneal staining when the changes from baseline were evaluated.
The most commonly reported adverse effect with OTX-101 and cyclosporine is burning upon instillation of the drops, which can affect patient compliance. With cyclosporine, about 17% of patients assigned to the 0.05% and 0.1% concentrations of cyclosporine A reported burning on instillation. In contrast, 1.3% of patients assigned to both OTX-101 concentrations reported severe discomfort.
In addition, the increased tear production with OTX-101 was seen at 12 weeks compared with that of cyclosporine, which the FDA approved based on increased tear production after 6 months.
“It is gratifying to see that [OTX-101] is so well tolerated and may soon provide our patients with dry eyes another clinically proven effective treatment,” Dr. Martel said. “I have been very impressed with its clinical efficacy.”
The FDA directed that one phase III trial be conducted to confirm the significant increase in tear production and the significant decrease in inflammation of the ocular surface compared with placebo resulting from instillation of OTX-101 in the phase IIb/III clinical trial. This confirmatory study has begun, according to a March 3 press release issued by Auven Therapeutics.
A long-term safety study will be conducted concurrently. The manufacturer anticipates that if these studies are successful, a new drug application will be submitted in 2017.