SONATA: 50% Adverse Event Rate Reported for Lifitegrast

Laird Harrison

April 29, 2015

SAN DIEGO — About half the patients with dry eyes who were treated with the experimental drug lifitegrast reported adverse events, a new study shows.

However, "there were no vision-threatening adverse events," said Eric Donnenfeld, MD, from New York University in New York City.

The news on lifitegrast is important, said session discussant Bennie Jeng, MD, from the University of Maryland in Baltimore. "This is very interesting because the mechanism is novel," he told Medscape Medical News. "If it can be shown definitely to work and it's pretty safe, it's going to be big."

Dr Donnenfeld presented results from the SONATA trial here at the World Cornea Congress.

Working on the theory that dry eye can be caused, at least in part, by inflammation, researchers at SARcode Bioscience, a subsidiary of Shire, developed lifitegrast to prevent lymphocyte-function-associated antigen from binding to native intercellular adhesion molecule 1, which is expressed on the surface of inflamed epithelial cells.

The drug got mixed results in two phase 3 trials, as previously reported by Medscape Medical News. In OPUS-1, the drug improved signs but not symptoms of the dry eye, and in OPUS-2, it improved symptoms but not signs. The company is now working on OPUS-3.

In the meantime, Shire announced earlier this month that lifitegrast will undergo priority review by the US Food and Drug Administration.

Novel Mechanism

As part of its application, Shire conducted a multicenter, randomized, prospective, double-masked, placebo-controlled phase 3 safety study.

Dr Donnenfeld and colleagues recruited 331 patients with dry eye disease. The patients had Schirmer's test scores from 1 to 10 mm without anesthesia and corneal staining scores above 2.

During the 1-year study period, 220 patients were randomly assigned to receive lifitegrast 5.0% ophthalmic solution drops twice daily and 111 were assigned to placebo.

There were no serious ocular treatment-emergent adverse events in either group, but more patients in the lifitegrast group than in the placebo group experienced adverse events, and more patients in the lifitegrast group withdrew because of these events.

Table. Treatment-Emergent Adverse Events

Adverse Events Placebo Group, % Lifitegrast Group, %
Events leading to discontinuation 9.0 12.3
At least 1 ocular event 34.2 53.6
At least 1 nonocular event 36.0 47.3
Events probably related to treatment 24.3 47.3


The most common adverse events considered to be related to treatment were dysgeusia and instillation-site irritation or reaction. Both of these occurred more frequently in the lifitegrast group.

The researchers found no clinically significant changes in secondary safety measures. At 360 days, the mean plasma lifitegrast concentration was 0.047 ng/mL of blood.

"Lifitegrast appears to be very safe by the standards we looked at," Dr Donnenfeld told Medscape Medical News.

This study was funded by Shire. Dr Donnenfeld is a consultant to Shire. Dr Jeng reports financial relationships with Santen Pharmaceutical, Kedrion Biopharma, and Jade Therapeutics.

World Cornea Congress (WCC) VII. Presented April 17, 2015.


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