FDA Letters Issued in November 2025

This is a Complete Response letter from the FDA regarding CooperSurgical, Inc.'s supplemental New Drug Application (sNDA) for Paragard (intrauterine copper contraceptive), specifically for a new inserter. The application cannot be approved in its current form due to an incomplete facility inspection and numerous deficiencies identified in prescribing information, carton and container labeling, and the placement guide. The letter outlines detailed recommendations and requirements for resubmission, including a comprehensive safety update.

The FDA issued a 'not approvable' letter for New Drug Application (NDA) 21-164 for Gepirone Hydrochloride Extended Release tablets, citing a lack of substantial evidence for its effectiveness in treating major depressive disorder (MDD) and several Chemistry, Manufacturing, and Controls (CMC) deficiencies. The agency found that only 2 out of 12 studies showed a significant effect, with active comparators often outperforming gepirone ER, and a meta-analysis of the failed studies showed no significant effect. Additionally, the longer-term maintenance efficacy trial yielded negative results, and the applicant's post-hoc attempt to repair it was deemed invalid. The FDA also noted deficiencies in impurity acceptance criteria and stability data.

The FDA issued a 'not approvable' letter for Kyowa Pharmaceutical, Inc.'s New Drug Application (NDA 22-075) for istradefylline tablets (20mg, 40mg) due to inadequate information. The deficiencies cited include insufficient clinical evidence of meaningful benefit beyond a modest effect on 'OFF time' in Parkinson's Disease, required Phase 4 clinical pharmacology commitments, and incomplete nonclinical data regarding brain mineralization.

This document is a Complete Response Letter from the FDA to Mallinckrodt Hospital Products IP Limited regarding New Drug Application (NDA) 022231 for Terlivaz (terlipressin) 1 mg injection. The FDA has determined that the application cannot be approved in its current form due to concerns about the risk-benefit profile, particularly regarding the incidence of serious adverse events like respiratory failure, and unresolved questions about the clinical significance of the primary endpoint. The letter outlines specific deficiencies and required actions for resubmission.

This is a Complete Response letter from the FDA to Cyclomedica Australia Pty Ltd. regarding their New Drug Application (NDA) for Technegas™ Technetium Tc-99m carbon aerosol. The FDA has determined that the application cannot be approved in its present form due to various deficiencies across product quality (drug substance, drug product, process, device) and clinical aspects, and provides recommendations for addressing these issues.

This is a Complete Response letter from the FDA to Cadence Pharmaceuticals regarding their New Drug Application (NDA) for Ofirmev (acetaminophen) Injection. The FDA has determined that the application cannot be approved in its present form due to deficiencies related to facility inspections, labeling, and the need for a comprehensive safety update.

The FDA issued a Complete Response letter for Ferring Pharmaceuticals Inc.'s New Drug Application (NDA 022517) for Nocdurna (desmopressin) Orally Disintegrating Tablets. The application cannot be approved in its current form due to insufficient evidence that the drug's effect on nocturnal voids is clinically meaningful and outweighs the risks of hyponatremia. The FDA recommends conducting a new clinical trial to demonstrate meaningful clinical benefit using patient-reported outcomes and to prospectively evaluate hyponatremia monitoring strategies. The letter also outlines requirements for updating prescribing information, resubmitting the proprietary name, and providing a comprehensive safety update, including data from all nonclinical and clinical studies.

The FDA issued a Complete Response letter for NDA 022561 for cladribine tablets, indicating that the application cannot be approved in its current form. While cladribine was found effective for relapsing remitting multiple sclerosis (RRMS), significant safety concerns, particularly an increased risk of malignancy and lymphopenia, outweigh its benefits. The letter details specific deficiencies in clinical safety data, product quality, and labeling, requiring the applicant to provide additional analyses, studies, and information before resubmission.

This is a Complete Response letter from the FDA to Amgen, Inc. regarding Biologics License Application (BLA) 125522/Original 2 for Repatha (evolocumab). The FDA has determined that the application cannot be approved in its present form due to insufficient clinical data for the proposed 420 mg every two weeks dosing regimen for homozygous familial hypercholesterolemia (HoFH). The letter outlines specific deficiencies and provides recommendations for resubmission, including requirements for additional clinical data, a comprehensive safety update, and labeling revisions.

The document comprises multiple "Complete Response" letters from the FDA to Sun Pharma regarding New Drug Application (NDA) 204417 for Elepsia XR (levetiracetam) extended-release tablets. The letters consistently state that the application cannot be approved in its current form due to unresolved manufacturing facility deficiencies, issues with prescribing information (dosing, format, and content), and, in an earlier letter, concerns regarding bioequivalence data in the fed state and the similarity of plasma concentration-time curves compared to the reference listed drug.

This document is a Complete Response Letter from the FDA to ELC Group regarding New Drug Application (NDA) 205054 for Lutrate®Depot (leuprolide acetate for injection). The FDA has determined that the application cannot be approved in its present form due to deficiencies in clinical/statistical data, product quality, regulatory compliance, prescribing information, proprietary name, facility inspections, and safety update requirements.

The FDA issued two Complete Response letters for New Drug Application (NDA) 208574 for Romidepsin Injection, indicating that the application cannot be approved in its present form. The letters cite deficiencies related to manufacturing facilities (Teva Parenteral Medicines, Inc. and Teva Pharmaceutical Works Private Limited Company), product quality, and require comprehensive safety updates and revisions to prescribing information.

This is a Complete Response Letter from the FDA to AcelRx Pharmaceuticals, Inc. regarding their New Drug Application (NDA) 209128 for DSUVIA (sufentanil sublingual tablet). The FDA has determined that the application cannot be approved in its present form due to deficiencies related to safety, human factors, prescribing information, proprietary name, Risk Evaluation and Mitigation Strategy (REMS), safety update requirements, and container/carton labeling.

This is a Complete Response letter from the FDA regarding New Drug Application (NDA) 211150/Original 2 for Wakix (pitolisant) for the treatment of cataplexy in adult patients with narcolepsy. The FDA has determined that the application cannot be approved in its present form due to a lack of substantial evidence of effectiveness, citing inadequacies in the submitted clinical trials (HARMONY I and HARMONY CTP). The letter outlines the specific deficiencies and provides a path forward, including the requirement for an additional randomized, double-blind, placebo-controlled study.

This letter from the FDA identifies deficiencies in NDA 212097/S-012, specifically regarding dose accuracy testing, chemistry, manufacturing, and controls (CMC) for IV administration, prescribing information, proprietary name resubmission, and a comprehensive safety update. The applicant is required to address these deficiencies within one year to avoid withdrawal of the application.

This is a Complete Response Letter from the FDA to Therakind Limited regarding New Drug Application (NDA) 212479 for Jylamvo (methotrexate) oral solution. The FDA has determined that the application cannot be approved in its present form due to product quality issues related to a manufacturing facility and deficiencies in labeling and safety update submissions.

This FDA letter communicates deficiencies and requirements for the approval of New Drug Application (NDA) 212782. It addresses issues related to prescribing information, carton and container labeling, manufacturing facility inspections, product quality, and safety updates, requiring the applicant to submit a comprehensive response within one year.

The FDA issued Complete Response letters for New Drug Applications (NDAs) 212887 (VOCABRIA) and 212888 (CABENUVA) from ViiV Healthcare Company, indicating that neither application can be approved in its current form due to various deficiencies. Approval of VOCABRIA is contingent on CABENUVA's approval.

This is a Complete Response letter from the FDA to AVEO Pharmaceuticals, Inc. regarding their New Drug Application (NDA 204408) for tivozanib hydrochloride capsules. The FDA has determined that the application cannot be approved in its current form due to deficiencies in clinical data (inconsistent progression-free survival and overall survival results, uninterpretable trial results), product quality (unsupported dissolution acceptance criterion), and pending labeling review. The letter outlines specific recommendations and requirements for addressing these issues for a potential resubmission.

This is a Complete Response Letter from the FDA to Alkermes, Inc. regarding New Drug Application (NDA) 213378 for Lybalvi (olanzapine and samidorphan). The FDA has determined that the application cannot be approved in its present form due to objectionable conditions at a manufacturing facility, pending review of prescribing information, and outstanding clinical data requirements.

This document is a Complete Response letter from the FDA to Genentech, Incorporated, regarding their New Drug Applications (NDAs) and supplemental NDAs (sNDAs) for XOFLUZA (baloxavir marboxil) for the treatment and post-exposure prophylaxis of influenza in pediatric patients. The FDA determined that the applications cannot be approved in their present form due to concerns primarily related to the high frequency of treatment-emergent resistance in pediatric patients and the potential risk of transmission of resistant virus.

This document is a Complete Response letter from the FDA to Gilead Sciences, Inc. regarding their New Drug Applications (NDAs) for lenacapavir injection (NDA 215973) and lenacapavir tablet (NDA 215974). The FDA has determined that the applications cannot be approved in their current form due to various deficiencies related to product quality, prescribing information, proprietary name, and safety updates. The letter outlines specific issues and provides recommendations for addressing them.

This document is a deficiency letter from the FDA regarding New Drug Application (NDA) 216190, outlining specific deficiencies related to prescribing information, carton and container labeling, proprietary name, and a comprehensive safety update. It also details the process for resubmission or other actions, including potential withdrawal if no action is taken within one year.

The FDA issued a Complete Response letter for NDA 217186 for Crexont (carbidopa and levodopa) Extended Release Capsules, indicating that the application cannot be approved in its current form due to insufficient scientific bridging for carbidopa pharmacokinetic exposure and inadequate long-term safety data.

This is a Complete Response letter from the FDA to Astellas Pharma US, Inc. regarding their supplemental New Drug Application (sNDA) for IZERVAY (avacincaptad pegol intravitreal solution). The FDA has determined that the application cannot be approved in its present form due to insufficient data supporting an expanded dosing regimen and outlines deficiencies and recommendations for resubmission.

The FDA issued a Complete Response letter for Azurity Pharmaceuticals, Inc.'s New Drug Application (NDA) 219122 for sitagliptin oral solution, indicating that the application cannot be approved in its current form due to outstanding deficiencies related to facility inspections, prescribing information, proprietary name, and safety updates.

This is a Complete Response letter from the FDA to Eli Lilly and Company regarding their Biologics License Application (BLA) 761215/Original 2 for Rezvoglar (insulin glargine-aglr) injection, seeking interchangeability with U.S.-licensed Lantus. The FDA has determined that the application cannot be approved in its present form, primarily due to the unexpired exclusivity period for a prior interchangeable biological product. The letter outlines regulatory reasons for non-approval, reserves comment on labeling, and details requirements for a safety update if the application is resubmitted.

This is a Complete Response Letter from the FDA to Citius Pharmaceuticals, Inc. regarding their Biologics License Application (BLA) for Lymphir (denileukin diftitox-cxdl) for injection. The FDA has determined that the application cannot be approved in its present form and outlines specific deficiencies and recommendations that must be addressed.

The FDA has issued a provisional determination for BLA 761338/Original 2 for Steqeyma (ustekinumab-stba) injection, finding it meets the interchangeability criteria with Stelara (ustekinumab). However, approval cannot be granted at this time due to unexpired exclusivity for the first interchangeable biosimilar biological products. The letter outlines deficiencies related to labeling, safety updates, and product quality (stability and compatibility studies), and provides instructions for resubmission to obtain eventual approval.

This letter from the FDA outlines deficiencies in a Biologics License Application (BLA 761367) and provides specific requirements for resubmission. It covers various aspects including filling capability data, prescribing information, proprietary name, safety updates, microbiology, product quality, and device performance, emphasizing the need for comprehensive data and adherence to regulatory standards for approval.

The FDA has issued a provisional determination that Pyzchiva (ustekinumab-ttwe) is interchangeable with Stelara (ustekinumab) for various formulations, but cannot approve the applications (BLA 761373/Original 2 and BLA 761425/Original 2) due to an unexpired period of exclusivity for the first interchangeable biosimilar biological products. The letter outlines the steps required for future approval once the exclusivity period expires, including submitting an amendment with updated information and fulfilling postmarketing commitments.

This is a Complete Response letter from the FDA to Eli Lilly and Company regarding their Biologics License Application (BLA) 761215/Original 2 for Rezvoglar (insulin glargine-aglr) injection, seeking interchangeability with U.S.-licensed Lantus. The FDA cannot approve the application in its current form primarily because the regulatory exclusivity period for the reference product has not yet expired, as stipulated by section 351(k)(6) of the Public Health Service Act. The letter also outlines specific requirements for a comprehensive safety update, potential labeling revisions, and the necessary next steps for resubmission or other actions.

This document comprises two FDA Complete Response Letters (CRLs) issued to Laboratorios Farmacéuticos ROVI, S.A. for their New Drug Application (NDA) 214835 for Risvan (risperidone ISM) intramuscular injectable suspension. The letters state that the application cannot be approved in its current form due to various deficiencies related to facility inspections, product quality, human factors, and prescribing information.