Lymphir (denileukin diftitox-cxdl) / Eisai, Citius Oncology - LARVOL DELTA

Eisai Satisfies All-Case Surveillance Requirement for Anticancer Agent Remitoro (Eisai Press Release) - "Eisai...announced today that it has received notification from Japan’s Ministry of Health, Labour, and Welfare (MHLW) that the 'all-case surveillance' post-marketing observational study condition required at the time of approval of anticancer agent 'Remitoro for Intravenous Drip Infusion 300μg' (Denileukin Diftitox (Genetical Recombination)) for the indications of T-cell Lymphoma has been cleared....Based on the safety data in 111 patients and efficacy data in 85 patients submitted to the MHLW as the results of analyses of this all-case surveillance, the MHLW has concluded that the all-case surveillance was conducted properly and the necessary measures to ensure proper use of the product were sufficient to lift the condition."

Japanese regulatory • T Cell Non-Hodgkin Lymphoma

Selecting appropriate therapy for cutaneous T-cell lymphomas (CTCLs): recent advances and the unmet need. (PubMed, Expert Opin Pharmacother) - No abstract available

Journal • Cutaneous T-cell Lymphoma • Hematological Malignancies • Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma

Effect of E7777 Immunogenicity on Pharmacokinetics, Efficacy, and Safety in Adult Patients With Relapsed or Refractory Cutaneous T-Cell Lymphoma. (PubMed, Clin Transl Sci) - "Serious TE adverse events were reported by 32.1% of TE E-ADA-positive patients, 29.0% of TE I-ADA-positive patients, 100% of E-ADA-negative patients, and 73.3% of I-ADA-negative patients. These results indicate that the presence of ADAs decreased E7777 exposure over time but did not adversely impact efficacy and safety in patients with CTCL."

Journal • PK/PD data • Cutaneous T-cell Lymphoma • Hematological Malignancies • Infectious Disease • Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma • IL2

Citius Pharmaceuticals and Citius Oncology Announce Unique Permanent J-Code Issued for LYMPHIR by Centers for Medicare and Medicaid Services (PRNewswire) - "Citius Pharmaceuticals, Inc...today announced that LYMPHIR (denileukin diftitox-cxdl) has been assigned a unique, permanent Healthcare Common Procedure Coding System (HCPCS) J-code (J9161) by the Centers for Medicare & Medicaid Services (CMS)...Effective April 1, 2025, healthcare providers may use the permanent J-code, J9161 (Injection, denileukin diftitox-cxdl, for intravenous use, 1 microgram), when submitting claims for LYMPHIR."

Medicaid • Medicare • Cutaneous T-cell Lymphoma

Study of E7777 Prior to Kymriah for R/R DLBCL (clinicaltrials.gov) - P1/2 | N=30 | Recruiting | Sponsor: Masonic Cancer Center, University of Minnesota | Trial completion date: Dec 2024 ➔ Dec 2025 | Trial primary completion date: Dec 2024 ➔ Dec 2025

Trial completion date • Trial primary completion date • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • MYC

Citius Pharmaceuticals and Citius Oncology Highlight LYMPHIR Commercial Launch Planned for the First Half of 2025 (PRNewswire) - "Management is focused on making LYMPHIR available to patients as quickly as possible, with preparations underway for launch in the first half of 2025...Key Launch Preparations and Activities...Secured commercial supply agreements with leading contract manufacturing organizations (CMOs); First Year Launch Supply has been produced...Rolled out targeted education programs aimed at oncologists, hematologists, and other key medical professionals...Working closely with payers and healthcare providers to secure reimbursement pathways that facilitate patient access; Submitted an application for a unique J-code under the Healthcare Common Procedure Coding System (HCPCS) to streamline reimbursement processes; Secured LYMPHIR's inclusion in the National Comprehensive Cancer Network (NCCN) guidelines, a key factor in influencing clinical decision-making and payer coverage in the U.S....patient assistance program to help with financial support and access to LYMPHIR."

Commercial • Launch US • NCCN guideline • Cutaneous T-cell Lymphoma

Efficacy and Safety of Denileukin Diftitox-Cxdl, an Improved Purity Formulation of Denileukin Diftitox, in Patients With Relapsed or Refractory Cutaneous T-Cell Lymphoma (J Clin Oncol) - P3 | N=112 | NCT01871727 | Sponsor: Eisai Inc. | "The PEAS included 69 patients (median age, 64.0 years). The ORR was 36.2% (95% CI, 25.0 to 48.7), including 8.7% with complete response. The median DOR was 8.9 months (95% CI, 5.0 to not estimable), and the median (Q1-Q3) TTR was 1.4 (0.7-2.1) months. A total of 84.4% of patients showed decreased skin tumor burden, with 48.4% showing a ≥50% decrease. Treatment-emergent adverse events (TEAEs) of special interest, most of which were grade 1 or 2, included infusion reaction (73.9%), hypersensitivity (68.1%), hepatotoxicity (36.2%), and capillary leak syndrome (20.3% [grade ≥3, 5.8%])."

P3 data • Cutaneous T-cell Lymphoma

Efficacy and Safety of Denileukin Diftitox-Cxdl, an Improved Purity Formulation of Denileukin Diftitox, in Patients With Relapsed or Refractory Cutaneous T-Cell Lymphoma. (PubMed, J Clin Oncol) - "Efficacy and safety results show that DD-cxdl would potentially fulfill a serious, unmet medical need for patients with R/R CTCL."

Journal • Cutaneous T-cell Lymphoma • Dermatology • Fatigue • Hematological Malignancies • Hepatology • Immunology • Infectious Disease • Lymphoma • Mycosis Fungoides • Oncology • Sezary Syndrome • Skin Cancer • T Cell Non-Hodgkin Lymphoma • IL2

T-regulatory cell depletion with E7777 combined with pembrolizumab in patients with recurrent solid tumors: phase I trial (SITC 2024) - "Another patient had progressed on prior therapy including pembrolizumab combined with Lenvatinib. Initial efficacy data are encouraging including patients who progressed on prior anti-PD1 therapy. Ongoing translational work is ongoing to explore the impact on level of T-regulatory cells and CD8 T-cells and if it correlates with clinical benefit."

Clinical • P1 data • Oncology • Solid Tumor • CD8

Citius Pharmaceuticals, Inc. and Citius Oncology, Inc. Announce Promising Preliminary Results of an Investigator-Initiated Phase I Clinical Trial of Pembrolizumab (KEYTRUDA) and LYMPHIR in Cancer Patients with Recurrent Solid Tumors (PRNewswire) - P1/2 | N=70 | NCT05200559 | "The data was...presented at the Society for Immunotherapy of Cancer (SITC) 2024 Annual Meeting held November 8-10, 2024 (Abstract 614)...The results of this chemotherapy-free regimen combining two immuno-modulator agents, pembrolizumab (anti-PD-1) and LYMPHIR (transient Treg depletion) demonstrated: An overall response rate (ORR) of 27% (4/15) and a clinical benefit rate of 33% (5/15) among evaluable patients; and; Median progression-free survival (PFS) for patients achieving clinical benefit of 57 weeks, with a range of 30 to 96 weeks; Notably, two of the four patients who achieved partial remission had received prior checkpoint inhibitors (i.e. anti-PD-1 therapy). This highlights the therapeutic potential of LYMPHIR plus immune checkpoint inhibitors to be effective in patients who fail prior anti-PD-1/L1 therapy....The trial enrolled 21 patients with recurrent or metastatic solid tumors."

P1 data • Oncology • Solid Tumor

Citius Pharmaceuticals, Inc. and Citius Oncology, Inc. Announce LYMPHIR (Denileukin Diftitox-cxdl) Added to National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology (PRNewswire) - "Citius Pharmaceuticals, Inc...today announced that LYMPHIR has been added to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). LYMPHIR is included based on an NCCN Category 2A recommendation which indicates a uniform NCCN consensus that the drug is appropriate as an option for patients with Cutaneous T-cell Lymphoma (CTCL)."

NCCN guideline • Cutaneous T-cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

NCCN has published updates to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) and the NCCN Drugs & Biologics Compendium (NCCN Compendium) for Primary Cutaneous Lymphomas, Version 3.2024. (NCCN)

NCCN guideline • Cutaneous T-cell Lymphoma • Mycosis Fungoides • Sezary Syndrome

Citius Pharmaceuticals Receives FDA Approval for LYMPHIR (denileukin diftitox-cxdl) Immunotherapy for the Treatment of Adults with Relapsed or Refractory Cutaneous T-Cell Lymphoma (Citius Pharma Press Release) - "Citius Pharmaceuticals, Inc...announced today that the U.S. Food and Drug Administration (FDA) has approved LYMPHIR (denileukin diftitox-cxdl), a novel immunotherapy for the treatment of r/r cutaneous T-cell lymphoma (CTCL) after at least one prior systemic therapy...'The introduction of LYMPHIR, with its potential to rapidly reduce skin disease and control symptomatic itching without cumulative toxicity, is expected to expand the CTCL treatment landscape and grow the overall market, currently estimated to be $300-$400 million'...'We are preparing to launch LYMPHIR in the U.S. market within the next five months'...The approval of LYMPHIR is based on results from the Phase 3 Pivotal Study 302 (NCT01871727) of CTCL patients who had previously received at least one systemic treatment."

FDA approval • Launch US • Cutaneous T-cell Lymphoma • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology

Citius Pharmaceuticals Completes Merger of Subsidiary with TenX Keane to form Citius Oncology, Inc. (PRNewswire) - "Citius Pharmaceuticals...announced that it has completed the previously announced merger of its oncology subsidiary with TenX Keane Acquisition ('TenX')....The combined company will operate as Citius Oncology, Inc. ('Citius Oncology') and is expected to begin trading on August 13, 2024 on the Nasdaq stock exchange under the ticker symbol CTOR...."We believe a publicly traded Citius Oncology offers a unique pure play investment opportunity and is better positioned to unlock the value of LYMPHIR, which was approved by the FDA last week. With this transaction, we look forward to launching LYMPHIR, facilitating future growth initiatives, and exploring additional potential oncology assets'."

M&A • Cutaneous T-cell Lymphoma

Citius Pharmaceuticals Announces TenX Keane Shareholder Approval of Merger with Citius Oncology, Inc. (PRNewswire) - "Citius Pharmaceuticals, Inc...announced that shareholders of TenX Keane Acquisition...a publicly traded special purpose acquisition company, have voted to approve the previously announced business combination with Citius Pharma's oncology subsidiary. The transaction has been unanimously approved by the Board of Directors of both companies and Citius Pharma. Subject to certain contractual as well as customary closing conditions, the merger is expected to be completed in the coming weeks. The transaction is expected to provide Citius Oncology with improved access to the public equity markets, support the commercialization of LYMPHIR, if approved, and position the company to explore additional targeted oncology opportunities."

M&A • Cutaneous T-cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Citius Pharmaceuticals, Inc. Reports Fiscal Second Quarter 2024 Financial Results And Provides Business Update (Citius Pharma Press Release) - "LYMPHIR (denileukin diftitox) biologics license application (BLA) accepted by the U.S. Food and Drug Administration (FDA) with August 13, 2024, assigned as Prescription Drug User Fee Act (PDUFA) target action date...G&A expenses were $4.3 million for the quarter ended March 31, 2024, compared to $4.8 million for the quarter ended March 31, 2023. The decrease was primarily due to lower costs for pre-launch and market research activities associated with LYMPHIR during the period."

BLA • Commercial • PDUFA • Cutaneous T-cell Lymphoma

Citius Pharmaceuticals Announces Addition of City of Hope to UMN's Phase 1 Trial of LYMPHIR in Combination with CAR-T for the Treatment of B-Cell Lymphoma (PRNewswire) - "Citius Pharmaceuticals, Inc...today announced that the University of Minnesota Masonic Cancer Center intends to expand their ongoing investigator-initiated Phase 1 trial of LYMPHIR (denileukin diftitox) in combination with FDA-approved CAR-T products for the treatment of B-cell lymphomas. The ongoing study, led by Dr. Veronika Bachanova at the University of Minnesota (UMN), will include an additional study site at City of Hope (COH), a world-renowned cancer treatment and research institution, with Dr. Matthew Mei as the principal site investigator at COH. City of Hope is one of only 53 National Cancer Institute (NCI)-designated comprehensive cancer centers in the U.S....This Phase 1 dose-finding study to evaluate LYMPHIR prior to CAR-T therapies tisagenlecleucel (KYMRIAH), axicabtagene ciloleucel (YESCARTA), or lisocabtagene maraleucel/BREYANZI), in patients with B-cell lymphomas (BCL) (NCT0485523)..."

Trial status • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Citius Pharmaceuticals Announces FDA Acceptance of the BLA Resubmission of LYMPHIR (Denileukin Diftitox) for the Treatment of Adults with Relapsed or Refractory Cutaneous T-Cell Lymphoma (PRNewswire) - "Citius Pharmaceuticals...announced that the U.S. Food and Drug Administration (FDA) has accepted the resubmission of the Company's Biologics License Application (BLA) for LYMPHIR (denileukin diftitox), an IL-2-based immunotherapy for the treatment of patients with relapsed or refractory cutaneous T-cell lymphoma (CTCL) after at least one prior systemic therapy. The FDA has assigned a PDUFA goal date of August 13, 2024....The BLA is supported by a pivotal Phase 3 study (NCT01871727). The resubmission follows dialog with the FDA resulting from a Complete Response Letter (CRL) received on July 28, 2023."

BLA • PDUFA date • Cutaneous T-cell Lymphoma

Citius Pharmaceuticals Resubmits the Biologics License Application of LYMPHIR (Denileukin Diftitox) for the Treatment of Adults with Relapsed or Refractory Cutaneous T-Cell Lymphoma (PRNewswire) - "Citius Pharmaceuticals, Inc...announced the resubmission of the Company's Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for LYMPHIR (denileukin diftitox), an IL-2-based immunotherapy for the treatment of patients with relapsed or refractory cutaneous T-cell lymphoma (CTCL) after at least one prior systemic therapy....Based on Center for Drug Evaluation and Research timelines, FDA acceptance of the completed resubmission package and issuance of a Prescription Drug User Fee Act (PDUFA) date is expected within 30 days of resubmission."

BLA • PDUFA date • Cutaneous T-cell Lymphoma • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma

Citius Pharmaceuticals, Inc. Reports Fiscal Full Year 2023 Financial Results and Provides Business Update (PRNewswire) - "LYMPHIR™ BLA resubmission on track for early 2024....Completed Halo-Lido Phase 2b trial; end of Phase 2 meeting with FDA expected in early 2024....In early 2024, we plan to meet with the FDA to discuss the results of the trial and next steps in the Halo-Lido program...R&D expenses were $14.8 million for the full year ended September 30, 2023, compared to $17.7 million for the full year ended September 30, 2022. The decrease of $2.9 million is primarily associated with the completion of the LYMPHIR Phase 3 trial and the completion and submission of the related Biologics License Application to the FDA which was filed in September 2022."

BLA • Commercial • Cutaneous T-cell Lymphoma • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology

A Study of Remitoro in Participants With Recurrent or Refractory Peripheral T Cell Lymphoma and Cutaneous T Cell Lymphoma (All Case Study) (clinicaltrials.gov) - P=N/A | N=118 | Completed | Sponsor: Eisai Inc. | Recruiting ➔ Completed | N=85 ➔ 118 | Trial completion date: Nov 2026 ➔ Mar 2023 | Trial primary completion date: Nov 2026 ➔ Mar 2023

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Congestive Heart Failure • Cutaneous T-cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma

Targeting regulatory T cells by E7777 enhances CD8 T-cell-mediated anti-tumor activity and extends survival benefit of anti-PD-1 in solid tumor models. (PubMed, Front Immunol) - "This study evaluated whether adding E7777 (a new formulation of denileukin diftitox [DD]) improved the efficacy of anti-PD-1 antibody therapy. Treatment with E7777 was safe and well-tolerated. Combined E7777 and anti-PD-1 therapy was well tolerated and more effective than monotherapy with either drug."

Journal • Preclinical • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Hepatology • Infectious Disease • Liver Cancer • Oncology • Solid Tumor • IL2

Citius Pharmaceuticals Announces Publication in Frontiers of Immunology of Positive Results from Solid Tumor Study of LYMPHIR in Combination with Checkpoint Inhibitor (PRNewswire) - "Citius Pharmaceuticals, Inc...today announced that preclinical research on LYMPHIR ('denileukin diftitox' or 'E7777') was published today in Frontiers in Immunology....Targeting Tregs using LYMPHIR combined with anti-PD-1 (either sequentially or concurrently) demonstrated significant anti-tumor activity, and consistently targeted and transiently depleted Tregs in the tumor microenvironment; Combination treatment was more effective than monotherapy with either drug alone; Combination therapy was well-tolerated and significantly enhanced long-term survival in solid tumor-bearing animals."

Preclinical • Oncology • Solid Tumor

Citius Pharmaceuticals, Inc. Receives Regulatory Guidance from the U.S. Food and Drug Administration (FDA) regarding the Planned Resubmission of the BLA for LYMPHIR (PRNewswire) - "Citius Pharmaceuticals, Inc...is pleased to announce the Company has received additional guidance from the U.S. Food and Drug Administration (FDA) regarding the planned resubmission of the Company's Biologics License Application (BLA) for LYMPHIR™ (denileukin diftitox), an engineered IL-2-diphtheria toxin fusion protein for the treatment of patients with relapsed or refractory cutaneous T-cell lymphoma (CTCL) after at least one prior systemic therapy. The FDA has agreed with the Company's plans to address the requirements outlined in the complete response letter (CRL) received July 28, 2023. The guidance from the FDA provides Citius with a path for completing the necessary activities to support the resubmission of the Company's Biologics License Application (BLA) for denileukin diftitox. No additional clinical efficacy or safety trials have been requested by FDA for the resubmission."

FDA event • Cutaneous T-cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Citius Pharmaceuticals, Inc. Reports Fiscal Third Quarter 2023 Financial Results and Provides Business Update (PRNewswire) - "Citius to engage with the FDA to address enhanced product testing requirements identified in the complete response letter (CRL) for LYMPHIR™, received July 28, 2023, in preparation for resubmission; such efforts are not expected to impact Company's cash runway, which extends to August 2024...We expect that research and development expenses will stabilize in fiscal 2023 as we focus on the commercialization of LYMPHIR....G&A expenses were $3.7 million and $11.1 million for the three and nine months ended June 30, 2023, respectively, compared to $3.0 million and $9.0 million for the comparable periods ended June 30, 2022. The increase was primarily due to pre-launch and market research activities associated with LYMPHIR."

Commercial • Cutaneous T-cell Lymphoma • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology