Kala Pharmaceuticals EYSUVIS is the first FDA-approved short-term dry eye disease treatment.

Exacerbations, or “flares,” associated with dry eye disease (DED) are considered a lifelong consequence of the condition. Age, gender, climate, increased screen time, sleeping with a fan on at night — all may contribute to one’s susceptibility and make management more difficult.

The most alarming aspect about the disease, according to Sam Garg, MD, is that the prevalence is similarly impossible to quantify and likely affects more than the estimated 16 million Americans said to have been diagnosed with DED, according to Farrand et al in 2017. “Physicians will find some evidence of DED in the majority of patients,” says Dr. Garg, the vice chair of clinical ophthalmology, medical director, and associate professor of cataract, corneal, and refractive surgery at the Gavin Herbert Eye Institute of the University of California. “A lot of the most common problems we see really come down to dry eye — whether it’s tearing, itching, blepharitis, visual fluctuations, pain, foreign-body sensation or even blurry vision.”

For patients experiencing the fluctuating episodic dry eye flares, it can feel like a roller coaster of long-term management. This dynamic may soon change, however, with the FDA’s recent approval of a rapid-acting, short-term eyedrop that treats dry eye symptoms — EYSUVIS (loteprednol etabonate ophthalmic suspension) 0.25% from Kala Pharmaceuticals Inc. It is the first FDA-approved corticosteroid specifically for short-term treatment of DED.

“[EYSUVIS] gives providers a first-line prescription option to treat patients quickly with something that has proven efficacy,” Dr. Garg says.

QUICK ACTION

Intended to be used four times daily for up to 2 weeks, EYSUVIS utilizes Kala’s AMPPLIFY mucus-penetrating particle drug delivery technology to enhance distribution and penetration of loteprednol etabonate into ocular surface tissue to target the immune innate and adaptive responses that drive acute flares.

“It hits its target tissue — the cornea and conjunctiva — very well, and it’s metabolized very quickly so that you minimize side effects, such as IOP elevation. Other previously approved steroids may not share this side-effect profile,” explains Dr. Garg, an advisor for Kala. The proprietary AMPPLIFY delivery platform traps conventional particles in mucus, which “can decrease peak concentration in the cornea while surface coated mucus penetrating nanoparticles slip rather cleanly through the mucus to enhance distribution and penetration to the ocular surface.”

Kala says the product was evaluated in the largest clinical development program in DED to date, including three Phase 3 trials and one Phase 2 trial. EYSUVIS demonstrated rapid onset of relief for ocular discomfort observed as early as day 3. Statistical significance was achieved after 2 weeks of dosing for the sign endpoint of conjunctival hyperemia in all trials. Statistical significance was also observed in two of the three Phase 3 trials for the symptom endpoints of ocular discomfort severity in both the overall intent-to-treat (ITT) population and in a predefined subgroup of ITT patients experiencing more severe discomfort at baseline. EYSUVIS was reportedly well-tolerated across all four trials, with adverse events and IOP increases comparable to vehicle.

“The studies demonstrated a statistically significant improvement in terms of the ocular discomfort scale as early as day 4, along with the other pre-specified endpoints at day 8 and day 15,” Dr. Garg says.

INDICATIONS, AVOIDANCES

Dr. Garg believes EYSUVIS will be well-received by patients as first-line treatment because of its short-term rapid impact. “It can be difficult to have patients buy into a medication that will help them feel better ‘in a couple months,’ when they are symptomatic now,” he says. “The mainstays of treatment, such as artificial tears, compresses and other anti-inflammatories, are needed to manage ocular surface disease over the long term, but, even with good control, you’re going to have exacerbations. The technological advancements implemented offer a well-tolerated product … especially when considering steroid response we tend to see.”

Acknowledging that flares can remain challenging, Dr. Garg advises that patients administer EYSUVIS in concert with other treatments for conditions causing flares.

He also urges providers to supplement EYSUVIS with treatment of the eyelids. “Nearly 90% of patients with DED also have some component of a lid disease,” he says, citing a 2012 study by Lemp et al.

Dr. Garg does suggest not using the drops in patients with other masqueraders of ocular surface disease or pain, such as diagnosed viral, bacterial or fungal keratitis. Finally, chronic use of EYSUVIS has not yet been studied, so appropriate follow-up is important. Still, he notes, “Having a steroid approved for DED should help on the payer side of things as well, because now we shouldn’t be denied for a lack of an indication.” OM