FDA issues complete response letter to Aldeyra Therapeutics for reproxalap NDA
According to the company, an additional trial is required to show positive effects on the treatment of ocular symptoms in dry eye disease.
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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.
According to a news release from the company, while 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.1
The company noted in its news release, reproxalap is an investigational new drug candidate in development for the treatment of dry eye disease and allergic conjunctivitis, 2 of the largest markets in eye care.
Aldeyra also noted in its news release reproxalap is a first-in-class small-molecule modulator of RASP (reactive aldehyde species), which are elevated in ocular and systemic inflammatory disease. The mechanism of action of reproxalap has been supported by the demonstration of statistically significant and clinically relevant activity in multiple physiologically distinct late-phase clinical indications. Reproxalap has been studied in more than 2400 patients with no observed safety concerns; mild and transient instillation site irritation is the most commonly reported adverse event in clinical trials.
According to draft FDA dry eye disease guidance, efficacy in dry eye disease may be demonstrated with 2 symptom trials and 2 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 2023.1
The company noted in its news release 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.
Todd C. Brady, MD, PhD, president and CEO of Aldeyra Therapeutics, pointed out that with $143 million in cash, cash equivalents, and marketable securities as of September 30, 2023, the company is in position to conduct another symptom trial of reproxalap in patients with dry eye disease, with a potential NDA resubmission 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,” Brady said in the company’s news release.
Moreover, the company noted in its news release 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.1
