Aldeyra Therapeutics, Inc. announced receipt of a Complete Response Letter from the U.S. Food and Drug Administration (FDA) for the New Drug Application (NDA) of reproxalap, an investigational drug candidate, for the treatment of dry eye disease.
Although no safety or manufacturing issues with reproxalap were identified, the FDA stated in the letter that the NDA did not demonstrate “efficacy in treating ocular symptoms associated with dry eyes” and that “at least one additional adequate and well-controlled study to demonstrate a positive effect on the treatment of ocular symptoms of dry eye” should be conducted.
Per draft FDA dry eye disease guidance, efficacy in dry eye disease may be demonstrated with two symptom trials and two sign trials. Among other clinical trials, Aldeyra previously conducted two trials for ocular redness (a dry eye disease sign) as well as a dry eye disease symptom trial.
On November 16, 2023, Aldeyra submitted to the FDA a Special Protocol Assessment (SPA) for a dry eye disease chamber crossover clinical trial (the proposed trial) similar to the crossover chamber trial from which Aldeyra announced results on July 12, 2022. The SPA review cycle is anticipated to be 45 days, and Aldeyra expects FDA feedback from the SPA in December of 2023. The proposed trial is expected to cost less than $2 million, and top-line results are anticipated in the first half of 2024, subject to FDA feedback on the SPA.
The potential NDA resubmission is anticipated in the first half of 2024, pending FDA SPA feedback and positive results from the proposed trial.
Aldeyra intends to include in the potential NDA resubmission a draft label describing chronic and acute symptomatic benefit, in addition to acute reduction in ocular redness of reproxalap. The review period for the potential NDA resubmission is expected to be six months.
“With $143 million in cash, cash equivalents, and marketable securities as of September 30, 2023, we are well positioned to conduct another symptom trial of reproxalap in patients with dry eye disease, with a potential NDA resubmission in the first half of 2024,” stated Todd C. Brady, MD, PhD, president and CEO of Aldeyra Therapeutics. “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.”
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. Aldeyra plans to conduct a Type C meeting with the FDA in the first half of 2024 to discuss the potential NDA submission of reproxalap for the treatment of allergic conjunctivitis.
Aldeyra is extending previous cash runway guidance into late 2025, including clinical trial costs associated with the proposed trial and potential NDA resubmission; the initial commercialization and launch plans for reproxalap, if approved in late 2024; and continued early and late-stage development of its product candidates in ocular and systemic immune-mediated diseases. The extended cash runway guidance is based on Aldeyra’s current operating plan, which excludes any potential licensing or product revenue associated with reproxalap.