Regulators indicated that an additional trial would be needed to assess the efficacy of reproxalap to treat patients with dry eye. Aldeyra has submitted to the FDA a Special Protocol Assessment for the new trial.
The FDA has issued a complete response letter to Aldeyra Therapeutics for the new drug application (NDA) of reproxalap to treat patients with dry eye disease. Regulatory officials indicated that the NDA did not demonstrate efficacy in treating ocular symptoms associated with dry eyes and requested the company complete an additional adequate and well-controlled study to demonstrate a positive effect on the treatment of ocular symptoms of dry eye.
Dry eye disease is a common inflammatory disease estimated to affect 39 million or more adults in the United States. The disease is characterized by insufficient moisture and lubrication in the anterior surface of the eye, leading to dryness, inflammation, pain, discomfort, irritation, diminished quality of life, and in severe cases, permanent vision impairment.
Reproxalap is a first-in-class small-molecule modulator of RASP (reactive aldehyde species), which are elevated in ocular and systemic inflammatory disease. In patients with dry eye disease, RASP may contribute to ocular inflammation and changes in tear lipid composition.
For treatments for dry eye, the FDA requires two symptom trials and two disease sign trials. Aldeyra had conducted two trials for ocular redness (a dry eye disease sign), as well as a dry eye disease symptom trial.
The company has submitted a Special Protocol Assessment (SPA) for a dry eye disease chamber crossover clinical trial (its proposed new trial) similar to the crossover chamber trial from which Aldeyra announced results on July 12, 2022. Aldeyra expects FDA feedback from the SPA in December 2023, and top-line results are anticipated in the first half of 2024. If the SPA and proposed trial results are successful, Aldeyra expects to resubmit the NDA in the first half of 2024.
“If the SPA and proposed trial results are successful, and the potential resubmitted NDA is approved, the drug label may be the first label in dry eye disease to contain acute reduction in ocular redness, as well as a combination of chronic and acute symptomatic benefit, potentially highlighting the rapid activity of reproxalap on both signs and symptoms of dry eye disease,” Todd C. Brady, M.D., Ph.D., president and CEO of Aldeyra Therapeutics, said in a press release.
Aldeyra had submitted its application for reproxalap in November 2022 with safety and efficacy data from five clinical trials encompassing data for ocular dryness symptom score, ocular redness, Schirmer test, and Schirmer test ≥10 mm responder analysis. Results of the phase 3 TRANQUILITY-2 trial, which were released in June 2022, showed that reproxalap was statistically superior to vehicle for each of the two prespecified primary endpoints, Schirmer test and ≥10 mm Schirmer test responder proportions after a single day of dosing. The Schirmer test, a measure of ocular tear production, is the dry eye disease objective sign most commonly used for drug approval.
Reproxalap is also under development for the treatment of allergic conjunctivitis, a common inflammatory disease that affects an estimated 20% of the worldwide population. Results from the third positive phase 3 clinical trial of reproxalap in allergic conjunctivitis, the INVIGORATE-2 Trial, were announced on June 15, 2023.