Preliminary results from Aldeyra’s Phase III TRANQUILITY trial offer promise for patients with dry eye syndrome

GlobalData Healthcare 18th January 2021 (Last Updated January 18th, 2021 08:56)

Preliminary results from Aldeyra’s Phase III TRANQUILITY trial offer promise for patients with dry eye syndrome
The results announced earlier this month offer a glimpse into the potential of reproxalap to help improve signs and symptoms of DES. Credit: Shutterstock.

On 7 January, Aldeyra Therapeutics announced top-line results from the run-in cohort of the Phase III trial evaluating its product 0.25% reproxalap for patients with dry eye syndrome (DES). The positive impact of the therapy on endpoints such as ocular dryness, discomfort, and Schirmer’s test, although preliminary, signals an important advancement for DES patients compared to currently available treatment options.

Reproxalap is a small molecule with a mechanism of action (MOA) that is novel for DES. It is an inhibitor of reactive aldehyde species (RASP), compounds understood to contribute to ocular inflammation and cause a change in tear lipid composition. This anti-inflammatory action is in sharp contrast to that demonstrated by currently approved products such as Allergan’s Restasis (0.05% cyclosporine) and Novartis’ Xiidra (5% lifitegrast), both of which primarily interfere with the activation of T-cells.

The results announced earlier this month offer a glimpse into the potential of reproxalap to help improve signs and symptoms of DES. Out of the 23 patients who enrolled in the run-in cohort of the study, 12 patients were randomised to receive reproxalap and the remaining participants received the placebo. Compared to placebo, the intervention therapy was observed to be statistically superior in ocular dryness score and ocular discomfort score. A similar trend was also observed in endpoints such as ocular redness and Schirmer’s test score. If the final results from late-stage trials evaluating reproxalap are able to demonstrate a significant improvement in signs and symptoms of DES, then the molecule is likely to have a unique differentiation from currently available therapies, that is in the form of a first-in-class aldehyde trap therapy for this indication.

A number of factors can influence the market penetration of reproxalap should it receive approval for DES. Its quick onset of action is likely to be a key advantage over existing therapies and one that both patients and physicians will appreciate. Key opinion leaders (KOLs) interviewed by GlobalData have indicated that currently approved therapies such as Restasis (0.05% cyclosporine) can take a month to six weeks before their effect on DES symptoms can be felt. On the other hand, a primary concern related to reproxalap is the burden of dosing four times daily, a factor that could negatively impact patient compliance.

The fact that reproxalap represents a novel MOA in DES is one that raises an excitement in the field of DES. However, the anticipated entry of other pipeline agents with novel MOAs is likely to pose a challenge and can potentially limit the market share of reproxalap. Nonetheless, should any of these agents with novel MOAs receive approval and enter the market, it is expected to be a significant event that expands treatment opportunities for patients with DES.