Aldeyra shares spiral after a late-stage failure in dry eye disease — but that won't stop its pursuit of an NDA
Aldeyra Therapeutics’ shares tanked in premarket trading after the company admitted its dry eye candidate reproxalap missed the primary endpoint in a topline Phase III readout — but who needs the primary?
Despite the late-stage failure, Aldeyra is charging ahead with another Phase III trial, and CEO Todd Brady is confident a secondary endpoint will lead the candidate to success.
“We continue to advance reproxalap toward NDA submission as we focus on the completion of TRANQUILITY-2 and enrollment in the 12-month safety trial,” he said in a statement.
Investors weren’t as confident. $ALDX shares slipped more than 38% in premarket trading Tuesday, pricing in at $4.39 — a long fall from yesterday’s closing price of $7.13.
While reproxalap met the primary endpoint of ocular redness in a Phase II trial, the endpoint didn’t reach statistical significance in the Phase III TRANQUILITY readout, Aldeyra announced on Monday without providing any hard numbers.
It did, however, meet the secondary endpoint for dry eye disease based on the Schirmer test, which determines whether a patient’s eye produces enough tears. Again without providing the actual result, Aldeyra said the p-value there was 0.0001.
The Schirmer test has been accepted by the FDA as part of the basis for approval of other dry eye products, the Lexington, MA-based company said. So it’s going forth with another Phase III study, dubbed TRANQUILITY-2 — except this time, it’s modifying the trial so that the primary endpoint will be met if statistical significance is achieved in either ocular redness or the Schirmer test.
In addition, target enrollment has been upped from 300 to 400 patients, according to Aldeyra. Top-line results there are expected in mid-2022.
“Following the achievement of statistical significance in ocular redness in our recent Phase 2 clinical trial, the achievement of statistical significance of Schirmer test in TRANQUILITY may provide an additional option to satisfy the remaining objective sign requirement for dry eye disease NDA submission,” Brady said in a statement.
Investors cheered on Aldeyra a few years ago when reproxalap achieved statistical significance in a Phase IIb readout for two doses rated on the Four-Symptom Ocular Dryness Score and the Overall Ocular Discomfort Symptom Score. However, some careful observers noticed that the high dose hit at week 8, then lost statistical significance at week 12, while the low dose outperformed the high dose at week 12 — raising some questions about durability and dose response.
Pending the enrollment of an ongoing 12-month safety study and the outcome of TRANQUILITY-2, Brady says an NDA submission could come as soon as mid-2022.
This isn’t the industry’s only failure this year in dry eye disease.
In October, Ocular Therapeutix announced its lead experimental eye drug, OTX-CSI (cyclosporine intracanalicular insert), failed to hit the primary endpoint in a Phase II trial: increased tear production at 12 weeks as measured by the Schirmer test compared to the vehicle control group. Aerie’s dry eye disease drug also missed the primaries in a Phase IIb trial back in September, but the company said it would plunge right into two Phase III trials anyway.