With no well-controlled data to support its efficacy, the FDA rejected Aldeyra’s methotrexate injection for primary vitreoretinal lymphoma.
Pictured: Amber-colored eye/iStock, Kryuchka Yaroslav
Wednesday, the FDA denied Aldeyra Therapeutics’ application for ADX-2191 (methotrexate injection, USP), which the Massachusetts biotech was proposing to treat the rare eye cancer primary vitreoretinal lymphoma.
In its Complete Response Letter, the regulator pointed to the “lack of substantial evidence of effectiveness” and “lack of adequate and well-controlled investigations” to support ADX-2191’s approval. The FDA did not flag safety or manufacturing concerns.
Aldeyra’s stock was down 27% in response to the news.
Given that only 300 to 600 new patients are diagnosed every year with primary vitreoretinal lymphoma (PVRL), “we do not currently believe that randomized clinical trials of ADX-2191 in PVRL, a rare and fatal cancer with no approved therapy, are feasible,” Aldeyra CEO Todd Brady said in a prepared statement.
To address the current shortage of methotrexate and the lack of approved treatments for PVRL, the company will engage the FDA to identify a potential path to make ADX-2191 available to patients under an Expanded Access Program, Brady said.
PVRL is a rare and aggressive eye cancer that can lead to death when left unmanaged and has a median survival of less than five years. There are currently no approved cures for PVRL and patients are typically managed using compounded intravitreal injections of methotrexate. ADX-2191 had previously won the FDA’s Orphan Drug designation for this disease.
Aldeyra’s New Drug Application for ADX-2191, which the FDA accepted in March 2023, consisted mainly of safety data from the Phase III GUARD trial, a randomized and placebo-controlled trial enrolling more than 100 participants with proliferative vitreoretinopathy. GUARD found no treatment-emergent serious adverse events. The most common side effect was punctate keratitis, an eye disorder caused by the death of small groups of cells on the surface of the cornea, which was generally medium in severity.
To establish efficacy, the company relied on more than 30 years’ worth of scientific literature showing the therapeutic potential of methotrexate injections in PVRL.
Based on previous discussions with the FDA, Aldeyra decided not to run its own efficacy trial of ADX-2191 in this indication.
Aside from PVRL, ADX-2191 is also being developed for proliferative vitreoretinopathy and retinitis pigmentosa. Aldeyra completed enrollment in the Phase II retinitis pigmentosa study in March 2023 and expects top-line data this year.
Meanwhile, in proliferative vitreoretinopathy, the company announced that ADX-2191 met its primary endpoint in the first part of GUARD in October 2022. A Type C meeting with the FDA for this indication is scheduled later this year.
Tristan Manalac is an independent science writer based in metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com.
