The FDA has asked for another well-controlled trial to establish the efficacy of reproxalap in dry eye disease.
The FDA has handed Aldeyra Therapeutics’ investigational dry eye disease drug reproxalap its second rejection, citing the need for more data.
In a Complete Response Letter released Thursday, the FDA noted that reproxalap had “failed to demonstrate efficacy in adequate and well controlled studies in treating ocular symptoms associated with dry eyes,” according to Aldeyra’s news release. The regulator is asking for at least one more study to show the benefit of reproxalap in treating dry eye disease symptoms. The FDA did not identify safety or manufacturing issues, Aldeyra said.
Aldeyra’s shares have fallen 73% since the start of the week, from $6.80 apiece. On Friday, the stock rallied a bit but only to $1.83.
Despite the setback, Aldeyra CEO Todd Brady on Thursday sang a positive tune in a statement, pointing to “pending positive results from the ongoing clinical trials” of reproxalap. Aldeyra currently has three other reproxalap studies running: two dry eye chamber trials—each using different chambers—and a six-week field trial.
Aldeyra expects topline readouts for the field trial and the chamber trial in the second quarter and is planning to meet with the FDA to discuss the rejection in the coming weeks. These, according to Brady, would put the biotech on-track to resubmit a drug application for reproxalap by “mid-year 2025,” he said.
Reproxalap is an investigational small molecule drug that works by blocking reactive aldehyde species, which are present in high amounts during eye inflammation. Aldeyra first sought approval for reproxalap in 2023 but was rebuffed in November that year, with the FDA noting that the data package failed to establish reproxalap’s “efficacy in treating ocular symptoms associated with dry eyes.”
Less than a year later, in August 2024, Aldeyra posted a Phase III readout from a chamber trial, showing that reproxalap significantly improved ocular discomfort in patients after 80 to 100 minutes in the dry eye chamber. Aldeyra used these findings to support its resubmitted drug application, which the FDA accepted in November 2024.
“Reproxalap remains the only late-stage topical ocular therapy suitable for chronic administration to have potentially demonstrated acute reduction in ocular redness, as well as reduction in ocular discomfort, highlighting rapid and broad activity for both the signs and symptoms of dry eye disease,” Brady added in the company’s statement.
Aldeyra had $101 million in cash, cash equivalents and marketable securities at the end of 2024, according to its announcement on Thursday. The biotech expects its reproxalap trials this year to cost $6 million. The company has also completed multiple Phase III trials of reproxalap for treating allergic conjunctivitis.
In late October 2023, Aldeyra signed a deal to give AbbVie the option to get a co-license to develop, manufacture, and commercialize reproxalap in the U.S., with $1 million paid out immediately and $100 million due if AbbVie chooses to exercise the option, which to date it has not.
