On November 9, 2026 Aldeyra Therapeutics, Inc. ("Aldeyra" or the "Company") reported that the Company has formally requested that the Division of Ophthalmology (the "DO") of the U.S. Food and Drug Administration (the "FDA") submit a review jurisdiction request to the FDA’s Office of New Drugs (the "OND") recommending that review of the Company’s Investigational New Drug application (the "IND") for ADX-2191 for the treatment of primary vitreoretinal lymphoma ("PVRL") be transferred to the FDA’s Division of Hematologic Malignancies 2 ("DHM2"). Aldeyra made this request because lymphoma reviews are typically conducted by DHM2, which maintains expertise in local and systemic manifestations of hematogenous cancers. In connection with this request, Aldeyra notified the FDA that it had withdrawn the Special Protocol Assessment (the "SPA") protocol for ADX-2191 for the treatment of PVRL, which the DO had previously reviewed and agreed to. The submission of the review jurisdiction request is within the DO’s control, and any decision on the request is within the FDA’s discretion. While the jurisdictional request is pending, the Company does not expect to initiate the clinical trial contemplated by the SPA.
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The following risk factor supplements, and should be read together with, the risk factors previously disclosed under the heading "Risk Factors" in our Annual Report on Form 10-K for the year ended December 31, 2025 and our Quarterly Reports on Form 10-Q for the quarters ended March 31, 2026; June 30, 2026; and September 30, 2026.
We have requested that review of our Investigational New Drug application (the "IND") for ADX-2191 in primary vitreoretinal lymphoma be transferred to a different U.S. Food and Drug Administration (the "FDA") review division, and we have withdrawn our Special Protocol Assessment ("SPA") protocol for the planned clinical trial. As a result, the regulatory path for ADX-2191 in this indication is uncertain, may be significantly delayed, and may not lead to approval, and these actions could adversely affect our interactions with the FDA on our other programs, including reproxalap.
In June 2023, we received a Complete Response Letter for our New Drug Application ("NDA") for ADX-2191 for the treatment of primary vitreoretinal lymphoma ("PVRL"), which stated that there was a lack of substantial evidence of effectiveness due to a lack of adequate and well-controlled investigations. We subsequently reached agreement with the Division of Ophthalmology (the "DO") of the FDA under a SPA on the design and planned analysis of a clinical trial intended to support a resubmission of the NDA.
On November 9, 2026, we announced that we requested that the DO submit a review jurisdiction request to the FDA’s Office of New Drugs ("OND") recommending that review of the ADX-2191 IND be transferred to the Division of Hematologic Malignancies 2 ("DHM2"). In connection with this request, we notified the FDA that we had withdrawn the SPA protocol, and we will no longer have the benefit of the DO’s agreement on the design and planned analysis of the trial. The submission of the request is within the DO’s control, and the decision is within the FDA’s discretion. We cannot predict whether or when the DO will submit the request, what the DO will recommend, or whether or when the OND will make a decision. The OND may deny the request or transfer the IND to a division other than DHM2. If the IND remains with the DO, our withdrawal of the SPA and our transfer request could adversely affect the DO’s review of ADX-2191. If the IND is transferred, the new division will not be bound by any prior agreement or position of the DO, may disagree with the trial design or with positions the DO previously took, and may recommend different or additional trials, data, or analyses. The FDA has previously recommended trials for ADX-2191 for the treatment of proliferative vitreoretinopathy that we did not deem feasible, which led us to cease development in that indication, and we may reach a similar conclusion regarding the development of ADX-2191 for the treatment of PVRL.
While the jurisdictional request is pending, we do not expect to initiate the planned trial, and we expect that the clinical program for ADX-2191 for the treatment of PVRL will need to be redesigned. Any redesigned trial (or trials) may be larger, longer or more costly; may be more difficult to enroll given the rarity of PVRL; and could delay or prevent our ability to obtain the orphan drug exclusivity that may be available under the orphan drug designation we hold for ADX-2191 in PVRL, including if another methotrexate-based product obtains approval and orphan drug exclusivity for the same indication first.
Any of these outcomes could delay or prevent an NDA resubmission for, or approval of, ADX-2191 in PVRL; increase our costs; shorten our projected cash runway; require us to raise additional capital sooner than expected; and materially harm our business, financial condition, results of operations and stock price.
(Press release, Aldeyra Therapeutics, NOV 9, 2026, View Source [SID1234674461])