The last time a medication was approved for the treatment of dry eye syndrome? October 2003.  That medication was the blockbuster Restasis, still commanding the dry eye marketplace 13 years later. Over those 13 years, we've learned a lot more about dry eye and the 16 million Americans that are diagnosed and treated for it every year.  They suffer from symptoms like burning, watering, redness, blurry vision, and tired eyes. For many, even the best medical care available on the market is not enough to overcome their discomfort.  That's why the world is so excited for a new medication on the market.  Shire's Xiidra was FDA approved on July 12th for the treatment of the signs and symptoms of dry eye disease (Restasis is FDA approved to treat the signs of dry eye disease only). Slated to become commercially available this fall, there's still a lot about Xiidra that patients and eyecare providers don't know. We don't know the cost, we don't know exactly how patients will respond in our offices, we don't know how Xiidra will compete with Restasis, and we don't know how insurance coverage will look.  Here's what we do know so far:

via

What It Is:
Xiidra (lifitegrast 5%) is a non-steroidal anti-inflammatory eye drop, treating dry eye by disrupting the inflammatory cascade responsible for much of the discomfort and ocular surface changes associated with dry eye disease. It specifically targets intracellular adhesion molecule 1 (ICAM-1); Xiidra binds to proteins on the surface of white blood cells (leukocytes) where ICAM-1 would typically bind, thus blocking ICAM-1 from being able to attach and signal the inflammatory cascade. When ICAM-1 molecules bind to leukocytes, they signal T-cells (the body's main inflammatory cell unit) to the area.  Xiidra prevents this binding, and thus T-cells aren't signaled to migrat to the ocular tissue.  What does blocking the inflammatory cascade mean to you? Inflammation is what makes dry eye so miserable - redness, burning, and surface cell damage (called superficial punctate keratitis -- basically dried out corneal cells sloughing off the cornea creating symptoms like sharp pain and blurry vision).

Superficial punctate keratisis: when corneal surface epithelial cells dry out, the cell wall break and they begin to slough off.  The process can cause you to feel sharp, shooting pain and chronic discomfort and visual fluctuations. via

What It Does: 
In the clinical trials that earned Xiidra FDA approval, over 1000 people with dry eye disease were treated with Xiidra over the course of 12 weeks and the results were compared to placebo treatment. Patients being treated with Xiidra showed statistically significant improvement at Week 6 and Week 12 as compared to those on placebo eye drops in both the signs and symptoms of dry eye, as measured by a subjective symptom scoring questionnaire called the Eye Dryness Score (EDS) and inferior corneal staining (see superficial punctate keratitis above).

How It's Used:

• Like Restasis, Xiidra is dosed 1 drop in both eyes 2 times a day.  
• Clinical trials suggest that Xiidra will begin improving both the signs and symptoms of dry eye as early as 6 weeks into treatment, much faster than Restasis whose clinical trials showed improvement in signs of dry eye (judged by Shirmer score) at 6 months versus placebo.  
• Xiidra and Restasis both target the inflammatory cascade, but they do not target the same molecules so there is no scientific data that suggests they could not be used in combination. 
• Xiidra is pregnancy category C (meaning it was not tested for safety)
• Xiidra is approved for ages 17 and up
• Xiidra is not approved for use with contact lenses; you must remove contact lenses before insertion and wait 15 minutes before reinserting them.
• Side effects of Xiidra: 
• 5-25% of users experienced burning with drop insertion, altered or bad taste (called dysguesia), and blurry vision after insertion
• 1-5% of users reported adverse reactions of ocular redness, headache, watering eyes, runny nose, and ocular discharge

With the patent set to expire for Restasis this month, the dry eye world is poised to have a new option on the block with Shire's lifitegrast molecule that is just reporting Phase 3 clinical trial data.  When Restasis first hit the market in 2002, it was the first prescription available for dry eye, showing increased tear production for patients and an anti-inflammatory effect.  For over a decade Restasis has been your doctor's only prescription choice for a drop to help produce more tear film, but due to the varied issues that cause dry eye, it has not been a cure-all for every type of dry eye sufferer.  Here is what we know about the potential new kid on the block:

Lifitegrast is an anti-inflammatory molecule, working to reduce T-cell activation and cytokine release.  Anti-inflammatories like Restasis and lifitegrast theoretically combat dry eye by breaking the inflammatory cycle.  When your eye gets dry, redness and irritation result from increased inflammation on the eye's surface.  This inflammation appears to reduce normal tear film function, causing more dryness and more inflammation.  It is a never-ending circle of dryness, redness, and discomfort.  Both Restasis and lifitegrast are T-cell modulators, but it is theorized that lifitegrast will be faster-acting than the Restasis molecule. Restasis typically requires around 3 months (the lifespan of a T-cell) to begin effectively breaking the dry eye cycle, whereas early data suggests lifitegrast will begin having effects in as early as 2 weeks.  There are at this time no head-to-head studies that compare the two drugs.  Potentially they could even be used in combination for a greater effect!

Lifitegrast is completing Phase 3 FDA trials, and so far results have been mixed.  All trials so far compare lifitegrast to placebo (the vehicle in the drug).

SPK or corneal staining is a clinical sign of moderate to severe dryness. Unfortunately lifitegrast performed no better than its placebo at improving SPK on the surface of the eye in the OPUS-2 study.  Patients did however report improvement of their dry eye symptoms in the blind study.  via

In the OPUS-2 study, paitients reported a  statistically significant relief from dryness symptoms with lifitegrast versus placebo.  Unfortunately the clinical signs of dryness measured in the study (inferior corneal staining) was not statistically significantly improved with the use of the drug.  Thus continues the infuriating issue with dry eye -- symptoms and signs of dryness tend not to coincide.  So while patients felt better, the clinical findings of dryness and damage on the surface of the eye (corneal staining in this study) had not improved.

In the SONATA safety study, there were no reported dangerous side effects with lifitegrast use. The most common side effect was bad after-taste (16.2% of users) and irritation after installation (7.8%).  Burning with installation is also a common complaint with Restasis use.

While there is no way to accurately predict when or if lifitegrast will come to market as a true alternative or additive therapy to Restasis treatment, it can be several years before a drug with successful phase 3 trials actually makes it to market.  I will continue to keep you updated as we learn more!