Dry eye disease and allergic conjunctivitis are two flourishing markets within ophthalmology. The dry eye market is expected to climb to $5.1 billion by the year 2024, up from $3.5 billion in 2018.1 Up to 40% of the population has allergic conjunctivitis, although many do not seek medical care for it.2
The public company Aldeyra Therapeutics is targeting both of these markets with its reactive aldehyde species (RASP) inhibitor called reproxalap. (The company is also pursuing a therapy for proliferative vitreoretinopathy, a disease which currently does not have other approved treatment options.) Within ophthalmology, Aldeyra has Phase 3 programs under way both for the anterior and posterior segment: reproxalap 0.25% for dry eye disease and allergic conjunctivitis and ADX-2191 for proliferative vitreoretinopathy.
Lead candidate reproxalap is a small molecule RASP inhibitor that covalently binds free aldehydes and lowers excessive RASP levels. “RASP is a new immunological target that modulates TH1, TH2, and TH17 arms of the immune system at a very upstream and broad-based level,” said Todd Brady, MD, PhD, CEO & President of Aldeyra, during an innovation showcase at the Ophthalmology Innovation Summit last year.
“We have the potential to be the next novel entrant in the dry eye disease marketplace and the allergic conjunctivitis disease marketplace. By novel, I mean new drug, new target—not old drug, new target or new drug delivery,” Mr. Brady said.
The company’s two-part, randomized, vehicle-controlled RENEW trial for dry eye now has top-line results. In part 1 of the trial, 422 patients were randomized for reproxalap four times a day for 12 weeks (called the constant dosing group) or four times a day for 4 weeks, followed by reproxalap twice a day or vehicle for 8 weeks (induction-maintenance dosing). There was greater observed activity in the constant dosing group. The co-primary endpoint of patient-reported visual analog scale ocular dryness between weeks 2 and 12 was reached in the induction-maintenance dosing group, with activity seen as early as a week after therapy began. Reproxalap was well-tolerated, with transient, mild site irritation reported as the most common adverse effect.
Part 2 planned primary endpoints in the RENEW trial will be ocular dryness score and fluorescein nasal region ocular staining score. Part 2 will enroll about 400 patients per arm.
Aldeyra announced results from its Phase 3 allergic conjunctivitis ALLEVIATE trial last year during the American Academy of Ophthalmology’s annual conference. The trial met its primary endpoint of lowering patient-reported ocular itching relative to vehicle. In the trial, 318 patients were challenged topically with seasonal allergen and then randomized to 0.25% or 0.5% treatment or vehicle. Itch resolution was statistically greater for patients receiving reproxalap compared with vehicle.
“There was both strong activity and symptoms in terms of itching and investigator-assessed redness,” Mr. Brady said. “Allergic conjunctivitis affects one-third of the world, and one-third of them don’t do well with antihistamines. That’s one-ninth of the world.” Ultimately, that indicates a large market, he said.
The company’s Phase 3 INVIGORATE trial, which enrolled its first patient in late January, compares 0.25% reproxalap versus vehicle in an allergen chamber, with a primary endpoint of statistically significant reduction in ocular itching between drug and vehicle at the majority of 11 time points. The trial will include about 120 patients and is expected to be completed by the end of this year.
Looking at the back of the eye, when Aldeyra acquired the private company Helio Vision in early 2019 it added the Phase 3 candidate intravitreal methotrexate (ADX-2191) to its pipeline. ADX-2191 was designed to treat proliferative vitreoretinopathy, which affects 10% of those with retinal detachment. A Phase 1b trial with ADX-2191 showed reattachment success and tolerability. ADX-2191 has both an Orphan Drug Designation and a Fast-Track Designation from the U.S. Food and Drug Administration. The GUARD Phase 3 trial enrolled its first patient in December, with completed enrollment slated for next year.
The company’s late-stage ocular products in the pipeline remain the company’s focus, as the company has now put on hold the clinical development of topical dermal reproxalap to treat ichthyosis associated with Sjogren-Larsson Syndrome and ADX-1612 for post-transplant lymphoproliferative disorder. By concentrating on its ocular portfolio, company reports believe the company’s cash runway will stay solid through 2021.
Because reproxalap and ADX-629, another RASP inhibitor from the company, are structurally related to chloroquine and hydroxychloroquine, company leaders are testing these drugs for anti-inflammatory and antiviral activity to treat COVID-19 infection.
Formed in 2004 using seed money from Johnson & Johnson, Aldeyra has focused on RASP inhibitors for ocular inflammation and autoimmune disease. The company counts among its strengths a deep pipeline focused on immune-mediated diseases, near-term development catalysts, a large market potential, and solid cash position. Cash, cash equivalents, and marketable securities were $73.4 million as of Dec. 31. Aldeyra had a net loss of $60.8 million in 2019, according to its earnings report. First quarter 2020 earnings data was not yet available at press time.
1. Market Watch. Dry eye syndrome market size with $5.1 billion by 2024. July 12, 2019. https://www.marketwatch.com/press-release/dry-eye-syndrome-market-size-worth-us-51-billion-by-2024-cagr-65-imarc-group-2019-07-12
2. Azari AA and Barney NP. Conjunctivitis: A systematic review of diagnosis and treatment. JAMA. 2013;310:1721-1729.