Aldeyra Therapeutics’ dry eye drug helped relieve ocular redness in a phase 2 trial but merely “approached statistical significance” on a secondary endpoint of wetness in the eye.
We know you’re here for the unspun version of this story, and this is it: the secondary goal was not met.
The small biotech out of Lexington, Massachusetts pinned its hopes on ocular diseases, specifically reproxalap, after halting the clinical development of two systemic disease programs in 2020. The company bet that throwing all resources into ocular would keep things going as cash reserves were drained.
And the company has certainly gone all in: rather than wait for the results of the phase 2, Aldeyra already has two phase 3s underway in the same setting of the mixed bag mid-phase trial that's being reported today. Aldeyra narrowed the endpoint to eye redness rather than others key to dry eye disease for the remaining tests, even switching one of the late-stage tests to only focus on this measure.
Now, Aldeyra is reporting that reproxalap met the main goal of the phase 2 trial, which was to improve eye redness based on a test after patients were placed in a dry eye chamber.
The FDA and other experts have questioned whether a dry eye chamber can truly replicate real-world conditions that patients experience with dry eye. The devices simulate minimal humidity, high airflow and forced visual tasking, according to Aldeyra, but are not standard in trials for dry eye disease.
Patients were given four doses the day before entering the chamber and then two doses during the 90-minute exposure in the chamber.
On the secondary endpoint, patients did not score high enough on a test that ranked eye wetness to reach statistical significance after the initial dose, but the results were “directionally in favor of reproxalap” compared to placebo.
The therapy also failed on other secondary symptomatic measures including eye dryness and discomfort, although patients who received the treatment reported lower scores than the placebo group, meaning they saw at least some relief. No new safety signals were observed in the trial.
“Complementing our rapid and durable symptom control evidenced in three 12-week clinical trials, we are excited to announce achievement of statistical significance of an objective sign of dry eye disease in a well-controlled clinical trial,” said Aldeyra President and CEO Todd Brady, M.D., Ph.D. “Ocular redness may be the only dry eye disease sign that is of importance to patients, and the reduction in redness observed in this trial following reproxalap treatment potentially represents a major advance for the chronic treatment of dry eye disease.”
Brady is suggesting here that signs of dry eye disease—which are lab-confirmed assessments—like ocular redness, are more important than symptoms, but there's been plenty of debate between signs versus symptoms in this condition and what is most important for patients.
Luckily, there’s a study for that. A 2019 study published in the National Institutes of Health’s library defined the needs of dry eye patients. Red eyes were noted as the “most burdensome eye appearance aspect” by 37% of patients, but 77% said eye discomfort and sensitivity were the most bothering symptom overall. Eye dryness was rated by 76% of patients as the most burdensome symptom.
Reproxalap previously posted a mixed bag of evidence in a phase 2a dry eye trial and also failed another midstage study in allergic conjunctivitis. Aldeyra has two phase 3 trials of reproxalap ongoing, which are looking at ocular redness. The results are expected to be released by the end of the year.
The therapy is also being tested in a phase 3 trial of patients with allergic conjunctivitis. Aldeyra has several other assets in the pipeline including the phase 3 drug ADX-2191, which is in three indications including the retinal detachment complication called proliferative vitreoretinopathy and retinitis pigmentosa.
Reproxalap is a small molecule drug formulated as a solution that inhibits reactive aldehyde species, a substance that is associated with inflammation and is elevated in patients with ocular and systemic inflammatory disease.