Aldeyra's tears of joy fail to move investors

If at first you don’t succeed, keep tinkering. Aldeyra got a pivotal win today with reproxalap on the signs of dry eye disease at the second time of asking – but only after changing the primary endpoint analysis of the Tranquility-2 study, not once but twice.

The trial showed a benefit on both the Schirmer test, which measures tear production, and a Schirmer responder analysis. Assuming the FDA is on board with Aldeyra’s data package, reproxalap could be heading to market.

But after surging over 20% in premarket trading, Aldeyra was up just 4% this morning, suggesting that investors do not share the company’s confidence.

For approval in dry eye the FDA requires a project to show a benefit on both the signs and symptoms of the disorder in at least two clinical trials apiece. Regarding symptoms, Aldeyra’s strategy has long been clear: the group plans to use part one of the phase 3 Renew trial, as well as the phase 2 Formulation study, which found a benefit on ocular dryness.

Tranquility ripples

On signs, the situation is less straightforward. In December, the first pivotal trial, Tranquility, failed to hit its primary endpoint of ocular redness; however, it did show a benefit on the Schirmer test, a secondary endpoint (Aldeyra needs more Tranquility, December 21, 2021). In response to this, Aldeyra changed Tranquility-2 to evaluate ocular redness and the Schirmer test as co-primaries; it had previously had ocular redness as the sole primary endpoint.

Last month, the company tinkered again, ditching ocular redness from the primary outcome analysis and focusing fully on Schirmer.

This move looks to have paid off: a day after dosing, patients receiving reproxalap had a statistically significant increase in Schirmer test scores versus those on vehicle. Those in the reproxalap group were also significantly more likely to be responders, defined as at least a 10mm increase in tear production.