干眼症新药立他司特(Xiidra)上市

What is dry eye syndrome

Dry eye syndrome is a chronic ocular surface disease affected by a variety of related factors. It is due to abnormal tear quality, quantity and dynamics, which leads to tear film instability or ocular surface microenvironment imbalance. Pathological changes include ocular surface inflammatory reaction and damage, high tear osmolality, abnormal neurosensory, etc. Its main clinical manifestations are dry eyes, foreign body sensation, accompanied by symptoms such as photophobia, stinging, red eyes, and blurred vision. If left untreated, severe ocular surface disease will develop.

Nowadays, dry eye syndrome has become a common disease in ophthalmology clinics and accounts for a major part of all related eye diseases. According to statistics from the "Consensus of Dry Eye Experts in China (2020)", the incidence rate of dry eye disease in my country is between 21% and 30%. At least 300 million people suffer from dry eye syndrome, which means that on average, 1 in every 5 people will suffer from dry eye disease. Research results show that ocular surface inflammation is one of the key factors in dry eye. Suppressing the inflammatory reaction on the ocular surface, breaking the inflammatory cycle, and restoring the stability of the ocular surface are important development directions in the treatment of dry eye.

The four clinical stages of dry eye are: mild and temporary eye discomfort; chronic or severe pain accompanied by deterioration of visual function; severe dry eye and eyeball redness and swelling; partial fibrosis and multiple corneal wounds.

Ritalast drug introduction

Although there are many types of drugs currently used to treat dry eye syndrome, most of them are symptomatic treatments, mainly reducing and relieving symptoms. Nowadays, there is an urgent clinical need for specific drugs to treat dry eye syndrome. On July 11, 2016, Ritalast eye drops became the first new lymphocyte function-associated antigen 1 (LFA-1) antagonist drug approved by the US Food and Drug Administration for the treatment of dry eye syndrome.

Preservative-free, sterile eye drops formulated with an antagonist of the cell surface protein integrin lymphocyte-associated antigen (LFA-1). Ritalast binds to LFA-1 on the surface of leukocytes and can effectively block the reaction between LFA-1 and intercellular adhesion molecule-1 (ICAM-1). It can achieve the effect of treating dry eye by inhibiting the inflammatory response on the ocular surface. Compared with previous drugs for the treatment of dry eye syndrome, Ritalast can relieve the uncomfortable symptoms caused by dry eyes and has the characteristics of fast onset, high safety and good tolerance.

The mechanism of action of Ritalast

Ritalast is a new type of small molecule integrin inhibitor that can inhibit the activation of T cells and the release of inflammatory molecules, thereby inhibiting the inflammatory response of dry eye disease and achieving the effect of treating the symptoms and signs of dry eye.

Ritalast can bind to integrin LFA-1 (lymphocyte function-associated antigen-1) and block the interaction between LFA-1/ICAM-1 (intercellular adhesion molecule-1), thereby destroying T cell-mediated inflammatory responses.

Interactions between LFA-1 and ICAM-1 (intercellular adhesion molecule-1) are involved in various aspects of lymphocyte activation and migration. LFA-1 is a protein that exists on the surface of white blood cells. ICAM-1 is overexpressed in the cornea and conjunctiva of dry eye disease. The lFA-1/ICAM-1 (intercellular adhesion molecule-1) interaction can promote the formation of immune synapses, activate T cells, and migrate to target tissues.

Ritalast

In four prospective, double-blind, multi-center, randomized, drug-controlled trials, the clinical efficacy of Ritalast in treating dry eye symptoms and signs was confirmed: Dry eye symptoms were significantly improved in 14 days, and the endpoint of the clinical trial was reached in 84 days.

In a Phase II clinical trial of 230 patients with severe dry eye disease, 0.1%, 1%, or 5% of patients were treated with ritasilast twice daily for 84 days compared with placebo. The results showed that Ritalast (1% and 5%) significantly improved the low corneal staining score (ICSS) at 84 days after baseline, and Ritalast 5% significantly improved tear production at 14 days after baseline; all Ritalast groups significantly improved the Ocular Surface Disease Index (OSDI) at day 14, and the 1% and 5% Ritalast groups significantly improved OSDI vision-related subscale scores at days 14 and 84.

Currently, cyclosporine is the only targeted drug for dry eye disease with the same mechanism of action. Its efficacy is limited due to poor solubility, low bioavailability, and dose-related side effects. Ritalast is the first new drug approved by the U.S. Food and Drug Administration (FDA) that can improve and treat dry eye symptoms. It has quick effects and minimal side effects.