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According to incomplete statistics, from January to April 2025, the FDA rejected a total of 6 drugs, including "Double Ai Therapy" andThe dry eye drug Reproxalap has not been rejected by the FDA for the first time. Among the reasons, two drugs were rejected due to CMC issues, two drugs were rejected due to clinical data issues, and one drug was rejected due to third-party issues. The editor summarizes as follows:'%20fill='%23FFFFFF'%3E%3Crect%20x='249'%20y='126'%20width='1'%20height='1'%3E%3C/rect%3E%3C/g%3E%3C/g%3E%3C/svg%3E)
On January 16, 2025, Atara Biotherapeutics announced that the U.S. FDA rejected approval.The Biologics License Application (BLA) for its cell therapy Ebvallo (Tabelecleucel). The application is for use as a monotherapy to treat adult and pediatric patients aged 2 years and older with Epstein-Barr virus-positive (EBV+) post-transplant lymphoproliferative disease (PTLD), who have previously received at least one prior therapy, including regimens containing anti-CD20.According to the press release, the FDA's decision not to approve this time is only related to the inspection results of the third-party manufacturer. The CRL did not mention any deficiencies related to the manufacturing process, clinical efficacy, or clinical safety data in the BLA, and the FDA did not request any new clinical studies to support the approval of Ebvallo.Tab-cel is an allogeneic, "off-the-shelf" EBV-specific T-cell immunotherapy that can target and eliminate EBV-infected cells. In addition to treating EBV-positive post-transplant lymphoproliferative disease, it is currently in the early stages of development for other EBV-related hematologic malignancies and solid tumors.Affected by this, Atara's stock price plummeted by 40%.Nevertheless, Atara is seeking cooperation with the FDA, Pierre Fabre laboratories, and third-party manufacturers to achieve the approval of Ebvallo in the United States.Dr. Cokey Nguyen, CEO of Atara, stated, full of confidence for Ebvallo's final approval, and it may be approved within six months after reapplication. The EU granted EBVALLO marketing authorization in December 2022.Hengrui Pharma: "Double Ai" TherapyOn March 21, 2025, Hengrui Pharma announced that it had received a complete response letter from the FDA regarding the Biologics License Application for Camrelizumab in combination with Apatinib Mesylate for first-line treatment of patients with unresectable or metastatic hepatocellular carcinoma. In the response letter, the FDA indicated that further responses are required for the inspection of related manufacturing facilities but did not specify the exact reasons in the letter.According to statements from South Korea's HLB company, the reason for this FDA rejection is still related toCMC Issues of Camrelizumab Production and Quality ControlRelated. The reason for the first rejection of the "Double Ai" combination also involved CMC issues.In May 2024, Hengrui Pharma received the first complete response letter for this marketing application. In the response letter, the FDA stated that due to manufacturing site inspection deficiencies and travel restrictions in some countries, it was unable to fully complete the required Bioresearch Monitoring Program (BIMO) clinical inspections for this project, and therefore, the application could not be approved within the prescribed review period.In October of the same year, Hengrui Pharma announced that it had resubmitted the New Drug Application (NDA) to the FDA for the first-line treatment of liver cancer using camrelizumab injection in combination with apatinib mesylate tablets, and the application has been accepted.Hengrui Pharma stated that the relevant production site will be inspected again by the FDA in January 2025. The FDA confirmed that all issues identified in last year's CRL have been rectified, with only three new improvement requests raised. The company has proactively responded to these issues within the stipulated timeframe and has maintained close communication with the FDA. The company will take measures as soon as the specific reasons are confirmed and resubmit the application in the hope of obtaining approval.Milestone: Etripamil Nasal SprayOn March 28, the FDA refused to approve Milestone Pharmaceuticals' Cardamyst (etripamil) nasal spray for the treatment of paroxysmal supraventricular tachycardia (PSVT), causing the company's stock price to drop more than 60% after the announcement. Milestone noted that the Complete Response Letter (CRL) primarily focused on Chemistry, Manufacturing, and Controls (CMC) issues and did not involve clinical studies.In the CRL, the FDA requests: submission of supplementary information on nitrosamine impurities according to the new guidelines after the NDA submission; and conducting on-site inspections for equipment changes during the NDA review to ensure compliance with cGMP. Milestone Pharmaceuticals expressed disappointment with the CRL, stating that its team will evaluate the feedback and plans to request a Type A meeting with the FDA to discuss the CRL matters.Etripamil Nasal Spray (trade name CARDAMYST™) is a novel calcium channel blocker nasal spray developed by Milestone Pharmaceuticals for the treatment of paroxysmal supraventricular tachycardia (PSVT).On April 3, the U.S. FDA once again rejected the New Drug Application (NDA) for Reproxalap, an investigational dry eye disease drug developed by Aldeyra Therapeutics. Aldeyra plans to meet with the FDA in the coming weeks to discuss the specific content of this Complete Response Letter (CRL) and subsequent requirements.FDA explicitly stated that more clinical data is needed to support the efficacy of the drug, and required Aldeyra to complete at least one additional adequate and well-controlled clinical trial to ensure the effectiveness of reproxalap in improving ocular symptoms related to dry eye disease.The FDA has clearly focused on methodological issues, including baseline score differences between treatment arms, and their impact on result interpretation.Reproxalap is an inhibitor of Reactive Aldehyde Species (RASP). The levels of RASP increase during ocular or systemic inflammation, leading to eye inflammation, reduced tear secretion, eye redness, and changes in the lipid composition of tears. Many patients with dry eye disease have elevated levels of Reactive Aldehyde Species.In November 2023, the FDA issued a CRL regarding Aldeyra Therapeutics' NDA for Reproxalap in the treatment of dry eye disease, stating that Reproxalap failed to demonstrate efficacy in treating dry eye disease and similarly required at least one additional well-controlled and adequate trial to prove its effectiveness.April 18, 2025FDA Issues Complete Response Letter (CRL) to Regeneron, Rejecting EYLEA HD® (Aflibercept 8mg)sBLA for the extension of the dosing interval of the injection from a maximum of 16 weeks to 24 weeks.FDA Disagrees with Regeneron’s Proposal to Extend Dosing Intervals Further but Offers No Additional ExplanationEYLEA HD is approved for wet age-related macular degeneration (wAMD) and diabetic macular edema (DME) patients with a dosing interval of every 8 to 16 weeks, and for diabetic retinopathy (DR) patients with a dosing interval of every 8 to 12 weeks, following three initial monthly doses.Following FDA's Refusal to ExtendThe day before the dosing interval, the FDA had accepted Regeneron's application for the approval of Eylea HD for the treatment of macular edema following retinal vein occlusion (RVO), as well as the expansion of Eylea HD’s dosing frequency to once every four weeks across all approved indications.A supplemental Biologics License Application (sBLA) has been submitted and granted Priority Review. The current minimum dosing interval is once every eight weeks after the loading period, with the FDA's target approval date set for August 19, 2025.On April 28, the U.S. FDA issued a complete response letter to Telix Pharmaceuticals regarding its glioma imaging agent TLX-101-CDx (18F-floretyrosine or18F-FET, Pixclara) NDA, indicatingAdditional confirmatory clinical evidence is required.。Telix stated that there are several ways to address the CRL issue, including re-analyzing existing (unpublished) data or conducting additional clinical trials.Pixclara is a PET tracer used to characterize progressive or recurrent gliomas caused by treatment-related changes in adult and pediatric patients. FET PET has been incorporated into international clinical practice guidelines for glioma imaging, but currently, there is no FDA-approved targeted amino acid PET tracer available in the United States for imaging adult and pediatric brain cancer. Given that Pixclara has the potential to address a significant unmet medical need, it has been granted Orphan Drug designation and Fast Track designation by the FDA.Reference: Announcements from various companies
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