Drug Developers Show Renewed Interest in Ocular Allergies

The ocular allergy space has seen some renewed interest lately, with Food and Drug Administration approval of Santen Pharmaceutical’s new drug for vernal keratoconjunctivitis (VKC) and promising Phase III results from Aldeyra Therapeutics for an investigational drug for allergic conjunctivitis.

Verkazia for VKC

In June, Santen announced approval of Verkazia, a 0.1% cyclosporine ophthalmic emulsion for VKC in adults and children. VKC is a rare, recurrent allergic eye condition mainly occurring in children and adolescents that causes severe inflammation of the ocular surface. Symptoms include intense itching, pain, and light sensitivity; severe cases can lead to corneal ulcers or vision loss.

The drug is a prescription-only, cationic emulsion that works by inhibiting immune system T-cell activation, reducing the level of immune cells and mediators causing allergic inflammation. Verkazia also is available in more than 10 countries across Asia and Europe, and in Canada. FDA approval was based on data from the VEKTIS study and the Phase II/III NOVATIVE study.

“We haven’t had any new drug approvals in this arena for some time, so it’s exciting,” commented Paul Karpecki, OD, FAAO, clinical director of corneal services and advanced ocular surface disease at Kentucky Eye Institute, and a clinician for Gaddie Eye Centers. The product is unique in its formula as a cationic emulsion leading to improved tissue penetration compared with existing therapies, its 0.1% concentration, and the fact that it was studied specifically for VKC, he said.

“There’s nothing else on-label I’m aware of for VKC,” Dr. Karpecki said. “We also would treat these patients sometimes with steroids, but those aren’t good long-term therapies.”

VKC “is a rare but really critical condition that we face,” and it may be underdiagnosed, Dr. Karpecki added. Children often present with extra-large papillae under their upper eyelids, or Horner-Trantas dots (collections of white blood cells and cellular debris) on the limbuses of their eyes.

VEKTIS, a multicenter, multinational double-masked randomized safety study of 169 children ages 4 to 17, found symptom and quality-of-life improvement in three Verkazia treatment groups – four times a day (high dose), twice a day (low dose) plus vehicle, or vehicle four times a day for four months – with the high-dose group showing significant improvement over the vehicle groups.

Reproxalap for Conjunctivitis

Aldeyra announced positive results from its Phase III INVIGORATE clinical trial of 0.25% reproxalap ophthalmic solution in patients with allergic conjunctivitis, which achieved statistical significance for all endpoints. The randomized, double-masked, vehicle-controlled study enrolled 95 patients with allergic conjunctivitis. Patients treated with reproxalap reported statistically significant reductions in ocular itching and tearing, and investigators observed significantly reduced ocular redness.

The company said it plans to meet with the FDA in the second half of 2021 to discuss results and the potential submission of a new drug application. It also has tested reproxalap in allergic conjunctivitis in the Phase III ALLEVIATE trial, finding similar results, and in dry eye disease in its Phase III TRANQUILITY trial, which demonstrated statistically significant reductions in patient-reported ocular dryness scores and investigator-assessed ocular redness in dry eye. Full results from the TRANQUILITY trial are expected in the second half of 2021.

Reproxalap is a novel small-molecule, immune-modulating inhibitor of reactive aldehyde species (RASP), which are elevated in ocular and systemic inflammatory disease. RASP attacks the inflammation pathway “very upstream” in the cascade of events leading to activation of inflammatory factors, Dr. Karpecki said.

“It’s a drug that’s in Phase III trials for both dry eye and allergic conjunctivitis, so it will be interesting to see which approval comes first,” he said. Some 40% of all patients with allergic conjunctivitis also have dry eye symptoms, he noted. “I wouldn’t say it’s a niche, because it’s a huge population, but it could allow us to cover both conditions at the same time, which makes it very novel.”

Dr. Karpecki sits on an advisory board for Aldeyra.