Topical IL-1 receptor blocker manages signs, symptoms of dry eye

Take-Home

A therapeutic in development blocks interleukin-1-a major player in the initiation and maintenance of the inflammatory response-and may help patients with moderate to severe dry eye disease.

By Lynda Charters; Reviewed by Michael H. Goldstein, MD

Boston-Patients with moderate to severe dry eye disease may benefit from the effects of an advanced product candidate. The therapeutic (EBI-005, Eleven Biotherapeutics) blocks interleukin-1 (IL-1), a key player in the initiation and maintenance of the inflammatory response in dry eye disease.

“[This] may be a promising future option for managing patients with moderate to severe dry eye disease,” said Michael H. Goldstein, MD, MBA, assistant professor of ophthalmology, Tufts University School of Medicine, and co-director, Cornea, External Disease and Cataract Service, New England Eye Center, Boston.

“[The drug] has been validated preclinically to inhibit IL-1, a driver of dry eye disease,” he added. “It is safe and well tolerated, and resulted in a clinically relevant magnitude of improvement in the signs and symptoms of dry eye disease by 6 weeks compared with baseline.”

More in this issue:  A pharmacological approach to dry eye syndrome in GVHD

Identifying a need

In the United States, dry eye disease is very common, with about 19 million people having some dry eye symptoms and 7 million having moderate to severe dry eye syndrome. However, only one drug, cyclosporine ophthalmic emulsion 0.05% (Restasis, Allergan), has been approved by the FDA to treat dry eye.

In Europe, the prevalence of dry eye is similar to that in the United States. In China and Japan, the prevalence rates are even higher. Clinicians in Japan have three drug options from which to choose:

• Hyaluronic acid ophthalmic solution (Hyalein, Santen)

• Diquafosol tetrasodium (Diquas, Santen)

• Rebamipide (Mucosta, Otsuka)

A serious need exists for a new treatment for U.S. and European populations, Dr. Goldstein noted.

How it works

As an IL-1 inhibitor, the product is one of several therapies under development to treat dry eye. The drug works by blocking the signs and symptoms of dry eye.

“[Its] mechanism . . . has demonstrated activity related directly to dry eye signs and symptoms that is a very differentiated approach to development,” said Dr. Goldstein, who is also vice president of medical research, Eleven Biotherapeutics. “[The product] has a dual mechanism of blocking both ocular surface damage and hypergesia.”

Elevated levels of IL-1α and IL-1β drive ocular surface cellular signaling. The proposed mechanism of action is that the product blocks IL-1α and IL-1β signaling on inflammatory, epithelial, and nerve cells, he explained.

Studying the drug

In a phase Ib/IIa double-masked, placebo-controlled trial conducted at eight sites, investigators evaluated its safety and efficacy in 74 patients with moderate to severe dry eye. Patients were randomly assigned to receive either vehicle or one of two doses of the drug: 5 or 20 mg/ml.

Each patient instilled the drug three times daily over 6 weeks. All patients were evaluated for adverse events and underwent ophthalmic examination, corneal esthesiometry and pachymetry, ocular surface microbiology, and serum laboratory testing. Other evaluations included corneal fluorescein staining, completion of the Ocular Surface Disease Index (OSDI) questionnaire, and frequency of use of artificial tears.

Patients’ treatment response

The therapeutic was found to be safe and well tolerated by patients. No adverse events were reported in association with its instillation, according to Dr. Goldstein.

“[The drug] resulted in a statistically significant (p < 0.005) reduced use of artificial tears,” he said. “The patients who were treated with the drug used less than half of the amount of artificial tears.”

Further, patients treated with the drug had significant (p < 0.001 for all comparisons) improvements compared with baseline in the total corneal fluorescein staining with a reduction of 33%, a 36% improvement in the OSDI score, and a 46% decrease in ocular pain, Dr. Goldstein noted.

Patients with an OSDI score below 50 had the best response to the drug-specifically, 39% improvement in corneal staining, 41% improvement in the OSDI score, and 61% improvement in ocular pain.

“In addition, patients used significantly fewer doses of artificial tears on average than vehicle-treated patients,” Dr. Goldstein said.

Michael H. Goldstein, MD

E: Michael.Goldstein@elevenbio.com

This article was adapted from Dr. Goldstein’s presentation at the 2014 meeting of the American Society of Cataract and Refractive Surgery. Dr. Goldstein is an employee of and has equity in Eleven Biotherapeutics. EBI-005 is investigational productA  and not currently approved for clinical use.