It's safe to say that a lack of clinical trials in a drug application raises red flags for the FDA. That was the case for Aldeyra Therapeutics' bid for approval in a rare eye cancer, despite the company's prior discussions with the agency.
The company was hoping for approval of its drug candidate ADX-2191 in primary vitreoretinal lymphoma (PVRL), a rare and aggressive cancer with a median survival rate of less than five years, according to the company. The FDA in March accepted the company's application under priority review, prompting Aldeyra to plan a launch during the second half of this year.
ADX-2191 uses an injectable form of methotrexate, a cancer drug first approved in the 1950s. But the drug is currently in a shortage across the U.S., raising complications for running trials.
Now, with the FDA issuing a complete response letter, it’s unclear when the candidate can enter the market. But the company is holding out hope that ADX-2191 could reach patients through an Expanded Access Program.
The FDA flagged a “lack of substantial evidence of effectiveness” thanks to “a lack of adequate and well-controlled investigations” in Aldeyra’s application for approval, the company said in a release. The company didn’t conduct any clinical trials “based on prior discussions” with the agency, it noted.
Aldeyra “appreciates” the agency’s position on needing evidence from clinical trials, but it doesn’t think an ADX-2191 study in the rare and fatal disease is feasible, CEO Todd Brady, M.D., Ph.D., noted in the company’s statement.
“Given the current shortage of methotrexate, the lack of approved therapy for PVRL, and the desire to avoid potential safety risks associated with ocular injection of compounded formulations, we look forward to discussing with the FDA the potential for making ADX-2191 available to PVRL patients under an Expanded Access Program,” Brady added.
The program, which is sometimes called “compassionate use,” according to the FDA, allows patients with serious or immediately life-threatening conditions to access treatment options that haven’t been approved and are still being studied. To use a drug under expanded access, the potential patient benefits must outweigh the risks.
Methotrexate has been in short supply since March, with five different suppliers affected. Some doses should be back in stock over the summer, according to the American Society of Health-System Pharmacists.
ADX-2191 is also being studied in rare eye disease retinitis pigmentos as well as proliferative vitreoretinopathy, a complication of retinal detachment. The company will conduct a type C meeting with the FDA in the latter condition in the second half of this year to “discuss the completion” of clinical development, it noted.
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