Aldeyra spies FDA filing ahead for dry eye drug reproxalap
Aldeyra Therapeutics' dogged persistence with its drug eye disease therapy reproxalap – despite mixed results in a phase 3 trial – may be paying off.
The Massachusetts-based biotech said a meeting with the FDA to discuss the programme has given it the confidence to press ahead with filing for approval of the RASP modulator in the US later this year.
Prospects for reproxalap looked bleak last year, after the drug failed to improve on placebo in treating ocular redness, the primary endpoint of its TRANQUILITY phase 3 trial. Although, it did show improvement in other measures, including tear production.
In the aftermath of that result, it modified the design of its second phase 3 trial – TRANQUILITY 2 – to increase the number of patients enrolled and add in tear production, measured using the Schirmer test as a co-primary endpoint.
Earlier this year it relegated ocular redness to secondary status, leaving the Schirmer test as the sole outcome measure, which spooked some investors who were nervous that the tinkering might be perceived negatively by the FDA.
When TRANQUILITY 2 read out, it met the twin primary endpoints of an improvement on the Schirmer test and an increase in the number of patients achieving a threshold increase in tear production, but once again failed on the ocular redness measure.
The TRANQUILITY study data will be combined with the results of another phase 3 trial called RENEW, looking at ocular dryness, plus a pair of phase 2 trials with positive results on ocular redness and dryness, respectively.
Aldeyra's chief executive Todd Brady said the company is now confident it has "aligned with the FDA on the content of the regulatory package that will support what we expect to be a uniquely comprehensive […] submission for the treatment of dry eye disease, encompassing data demonstrating improvement that may occur within minutes of drug administration in symptoms and three different objective signs."
"In contrast to currently available dry eye therapies that may require weeks of administration to achieve even modest benefit, the rapid onset of activity of reproxalap observed in clinical trials represents a potential paradigm shift," he added.
Shares in Aldeyra fell slightly after the announcement, suggesting investors are still not convinced that reproxalap will make it to market or perhaps compete with established therapies when it gets there.
Lying in waits at the moment are well-entrenched therapies like Novartis' Xiidra (lifitegrast) and AbbVie's Restasis (cyclosporine), which are not considered to be particularly effective and have issues with side effects. Sales were, nevertheless, solid at $468 million and $1.29 billion respectively last year.
Reproxalap outperformed Xiidra in a phase 2 study on symptoms, including eye discomfort and itching, which will stand in its favour, but the category is heading for a shake-up with low-cost generic competitors to Restasis set to emerge in 2024.
More threatening perhaps to Aldeyra's programme is Bausch Health and Novaliq's NOV03 (perfluorohexyloctane), which has already been filed for approval after positive results from a second phase 3 trials were reported earlier this year.
NOV03 is being reviewed as a treatment for the signs and symptoms of dry eye disease associated with Meibomian gland dysfunction (MGD), a group which is estimated to account for the majority (around 90%) of patients with the condition.