Lifitegrast ophthalmic solution 5.0% (Shire Pharmaceuticals) administered twice daily for 1 year appeared safe and well-tolerated with no unexpected adverse events in a study.
Take-Home Message: Lifitegrast ophthalmic solution 5.0% (Shire Pharmaceuticals) administered twice daily for 1 year appeared safe and well-tolerated with no unexpected adverse events in a study.
By Lynda Charters, Reviewed by Eric D. Donnenfeld, MD
Rockville Centre, NY - Lifitegrast Ophthalmic Solution 5.0% (Shire Pharmaceuticals) seems to be a safe option for treating patients with dry eye. In a study of twice-daily treatment for 1 year, there were no unexpected treatment-related adverse events, and the adverse effects that did occur were similar to those associated with placebo. No patients experienced any serious ocular or non-ocular adverse events associated with the drug, according to Eric Donnenfeld, MD.
Lifitegrast is a novel topical integrin antagonist that works by binding to the integrin lymphocyte function-associated antigen-1 (LFA-1), a protein on lymphocytes, and blocking the interaction or adhesion of LFA-1 with its intercellular adhesion molecule-1 (ICAM-1). In patients with dry eye disease, ICAM-1 is over-expressed in the corneal and conjunctival tissues. The interaction of LFA-1 and ICAM-1 promotes inflammation resulting in T-cell activation and migration to the target tissues. Lifitegrast tested in vitro inhibited T-cell adhesion to ICAM-1 expressing cells and inhibited secretion of key inflammatory cytokines and other pro-inflammatory cytokines such as interleukin (IL)-1α, IL-1β, IL-2, IL-4, IL-5, and IL-13, all of which are associated with dry eye disease, according to Dr. Donnenfeld.
“Lifitigrast is an exciting molecule because it inhibits T-cell mediated inflammation associated with dry eye disease at several different points in the inflammatory cascade with an entirely new mechanism of action,” said Dr. Donnenfeld, who is a founding partner of Ophthalmic Consultants of Long Island and Connecticut, Rockville Centre, NY, clinical professor ophthalmology, New York University Medical Center, New York, and a trustee of Dartmouth Medical School.
The safety of lifitegrast was evaluated previously in the phase 3 OPUS-1 and OPUS-2 studies, in which the participants instilled the drug twice daily for 84 days. The results showed that the drug was generally well-tolerated in these subjects with dry eye disease. The results of the OPUS-3 efficacy study were release on Oct. 27, 2015, and showed highly significant improvement of dry eye disease for all of the primary and secondary endpoints.
Dr. Donnenfeld reported on the results of the SONATA Study, a 1-year, multicenter, randomized, placebo-controlled phase 3 study that was carried out in the U.S. Patients were 18 years or older with self-reported dry eye disease, a Schirmer’s test result without anesthesia of 1 mm or higher and 10 mm or less, a corneal staining score of 2.0 or higher, and use of an artificial tear for 6 months or less. Patients were randomly assigned 2 to 1 to lifitegrast (n=221 patients) or placebo (n=111 patients). The patients instilled lifitegrast or placebo twice daily for 1 year.
The primary objective of the SONATA study was determination of the percentage and severity of treatment-emergent adverse effects in the eye and systemically. The secondary study objectives involved ocular safety measures such as corneal staining, drop comfort, best-corrected visual acuity, results of slit-lamp biomicroscopy, IOP, and the results of a dilated fundus evaluation over seven examinations. The investigators also measured the blood concentrations of lifitegrast.
Dr. Donnenfeld reported that no serious ocular adverse events developed in this study population; 118 ocular adverse events were reported that included similar percentages of instillation site irritation and site reactions and transient decreases in vision. One hundred four non-ocular adverse events developed, the most notable of which was dysgeusia. More adverse events developed in the lifitegrast group compared with the placebo group.
He also noted that there were no clinically relevant changes in the best-corrected visual acuity, slit-lamp biomicroscopy and dilated funduscopy examination, IOP, or drop comfort. In addition, the corneal fluorescein staining did not worsen in any area in either group. Finally, no lifitegrast accumulated in the plasma over the course of the study.
“The percentage of treatment-emergent adverse effects was higher in the lifitegrast group compared with placebo. No serious ocular treatment-emergent adverse events developed. Few patients discontinued lifitegrast because of adverse events. The study showed no evidence of systemic toxicity or complications due to local immunosuppression. Other ocular safety parameters for lifitegrast were similar to placebo. Lifitegrast ophthalmic solution 5.0% administered twice daily for 1 year appeared safe and well-tolerated by the patients with no unexpected adverse events and a safety profile similar to that of the OPUS-1 and OPUS-2 trials,” Dr. Donnenfeld concluded.
Shire Pharmaceuticals announced that on Oct. 16, 2015, the FDA requested that an additional clinical study be performed as part of a complete response letter (CRL) to the company’s new drug application for lifitegrast for the signs and symptoms of dry eye disease in adults. The highly positive results of the OPUS-3 study will be resubmitted to the FDA during the first quarter of 2016.
Eric D. Donnenfeld, MD
Dr. Donnenfeld is a consultant for Shire Pharmaceuticals.