Aldeyra Therapeutics’ late-study primary endpoint switch has paid off. Weeks after disclosing the change to its dry eye disease phase 3 trial, the biotech has reported a hit against the new primary endpoint, teeing it up to find out what the FDA makes of the data set.
Late last year, a phase 3 clinical trial of Aldeyra’s reproxalap ophthalmic solution missed its primary goal, which looked at ocular redness, but hit on a secondary measure that used Schirmer’s test to determine if the participants produced enough tears to keep their eyes moist. The biotech responded by modifying its other phase 3 so a win on either ocular redness or Schirmer’s test would trigger a hit against the primary endpoint, before selecting the tear production measure as its sole decider of success last month.
Having made the changes, Aldeyra has emerged from the second phase 3 trial, TRANQUILITY-2, with a hit on the primary endpoint. Reproxalap beat placebo on the overall change from baseline on Schirmer’s test and the proportion of participants with at least a 10-mm change.
The question now is what the FDA will make of Aldeyra’s mid-study changes and the resulting clinical data. The biotech plans to file a new drug application that features data on ocular dryness symptom score, ocular redness and the two Schirmer measures "pending discussions" with the regulator.
While Aldeyra is pitching the data set as potentially “the most comprehensive NDA submission in dry eye disease to date,” the strength of the results depend on the value placed on Schirmer’s test. The biotech sent Cathleen McCabe, M.D., a dry eye disease specialist for The Eye Associates in Sarasota, out to make the case for the test.
“Schirmer test is an accepted method for measuring tear production and has been used in clinical studies for over 20 years,” McCabe said in a statement. “I am extremely encouraged about the Schirmer test results and the other clinical sign endpoint data produced by reproxalap, highlighting the broad therapeutic benefit this therapy may bring to patients suffering from dry eye disease.”
More information on the next steps should arrive later in the year. Aldeyra expects to meet with the FDA in the third quarter and, if all goes to plan, make the approval submission sometime after that, pending enrollment in the ongoing 12-month safety trial and results from a dry eye chamber crossover trial.
If the biotech wins approval, it will then need to carve out a space among other recent entrants to the dry eye disease market. Oyster Point Pharma won FDA approval for Tyrvaya late last year and a filing for approval of Bausch + Lomb and Novaliq’s NOV03 is planned for this year. The companies are looking to unseat incumbents such as AbbVie’s Restasis and Novartis’ Xiidra.