Aldeyra Therapeutics had prepared for the worst and now it's here. The FDA has rejected the dry eye drug reproxalap.
With the complete response letter in hand, the biotech has an ambitious plan to zip through a brand new trial to get the application back to the agency within the first half of 2024.
In October, Aldeyra warned that a rejection was likely after a meeting with the FDA revealed “substantive review issues” for a new drug application that had a decision date of Nov. 23. The agency flagged concerns about a lack of clinical evidence for the drug and requested additional data on reproxalap's chemistry, manufacturing and controls process.
The official complete response letter states that Aldeyra failed to demonstrate “efficacy in treating ocular symptoms associated with dry eyes,” according to a post-market release Monday. The regulator wants a new trial to show a positive effect on ocular symptoms of dry eye disease.
The FDA said that efficacy may be demonstrated for dry eye disease with two symptom trials and two sign trials, according to Aldeyra. The company has already undertaken two trials for ocular redness, which is a sign of the disease, and a dry eye disease symptom trial. Aldeyra submitted a special protocol assessment to the FDA on Nov. 16 requesting a dry eye disease chamber crossover clinical trial similar to one the biotech had previously conducted. Feedback from the FDA is expected to arrive in December.
Aldeyra expects the study to cost $2 million with topline results ready in the first half of 2024 if the FDA is happy with the special protocol assessment. The study can be conducted with the company's $143 million cash on hand, according to CEO Todd Brady, M.D., Ph.D.
If all of those pieces fall into place, the resubmission could come in the first half of 2024—so long as the results are positive, according to the company.
Reproxalap has proven troublesome throughout the drug development process. In November 2021, Aldeyra reported that the ophthalmic solution helped with redness during a phase 2 trial but missed on a secondary endpoint of wetness in the eye.
In late 2021, Aldeyra also reported that a phase 3 study missed the primary goal of improving ocular redness. The company switched up the main goal to focus on tear production, finding in June 2022 that the study was a success on that measure.
Now, Aldeyra plans to propose a label to the FDA that includes chronic and acute symptomatic benefits and acute reduction in ocular redness from reproxalap.
“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 a statement.
Aldeyra is also developing reproxalap in conjunctivitis and plans to meet with the FDA to discuss a new drug filing for that indication in the first half of 2024.