LYMPHIR is the only CTCL therapy that targets the interleukin-2 (IL-2) receptor found on malignant T-cells and Tregs. This is the first indication for LYMPHIR and the first FDA-approved product for Citius Pharma.
"LYMPHIR offers new hope for patients suffering from cutaneous T-cell lymphoma, a rare and chronic cancer characterized by debilitating skin lesions and severe itching. This approval is a significant milestone for CTCL patients. 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," stated Leonard Mazur, Chief Executive Officer of Citius Pharmaceuticals.
"LYMPHIR, with an initial indication in the treatment of CTCL, is the first of our pipeline candidates to receive FDA approval. Citius is dedicated to working closely with healthcare providers to ensure that all r/r CTCL patients have timely access to this important new therapy. We are preparing to launch LYMPHIR in the U.S. market within the next five months," added Mazur.
"We are grateful to the clinicians, patients, and researchers who contributed to the development of LYMPHIR. We believe LYMPHIR's unique IL-2 receptor-targeted treatment, which kills tumor cells directly, and concurrently depletes host Tregs in order to boost the body's immune response, is an important differentiator and offers clinically meaningful benefits to a significant percentage of r/r patients.
As the only IL-2 receptor-targeted immunotherapy for CTCL, LYMPHIR provides a novel and non-cross-resistant treatment option without cumulative toxicity for Stage I-III r/r patients for whom symptomatic skin involvement interferes with their daily quality of life. LYMPHIR's median time-to-response of only 1.4 months (min, max: 0.7, 5.6) offers many patients rapid skin relief," added Dr. Myron Czuczman, Chief Medical Officer of Citius Pharmaceuticals.
CTCL is a rare and often debilitating chronic non-Hodgkin lymphoma that primarily affects the skin. Approximately 2,500-3,000 patients are diagnosed each year with an estimated 40,000 living with the disease. Patients with r/r CTCL have limited treatment options. No universally defined single treatment is used to treat these patients with incurable cancer. Patients typically cycle through several skin-directed therapies before the cancer becomes resistant and/or progressive at which point systemic agents are needed to achieve effective disease control.
Reducing and controlling skin plaques and itching without cumulative toxicity is a primary goal of CTCL treatment. Systemic medicines are prescribed until the disease progresses again or when dose-limiting toxicity occurs, after which HCPs prescribe a different systemic medicine. LYMPHIR provides another viable option in the treatment landscape with unique benefits to patients. It offers a novel mechanism of action designed to target and eradicate malignant T-cells while preserving healthy tissue. It is the only treatment option that targets the IL-2 receptors found in T-cell lymphomas and Tregs.
"As a treating oncologist, I have seen the profound negative effect on the quality of life in patients with r/r CTCL. Given the long-term nature of the disease, pruritus, ulceration of the tumors, and secondary pyogenic skin infection, it is vital to get this skin involvement under control. LYMPHIR is the first therapeutic option in many years to offer hope of reducing skin disease, bringing us one step closer to filling the need for CTCL patients, particularly those that are not able to complete or continue prior therapies," stated Dr. Francine Foss, Professor of Hematology and Director of the Multidisciplinary T-cell Lymphoma Program at Yale Cancer Center, New Haven, CT.
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. Actual study patients received a median of 4 (min, max: 1, 18) prior anticancer therapies. The primary efficacy population includes 69 patients with stage I-III CTCL who were treated with denileukin diftitox-cxdl (9 μg /kg/day). The primary efficacy outcome measure was Objective Response Rate (ORR), as assessed by an Independent Review Committee (IRC). The ORR was 36.2%, (95% CI: 25.0-48.7), with 8.7% achieving a Complete Response (CR).
The median time to response was rapid at 1.41 months, with the majority of responders (~70%) seeing results after 1–2 cycles of treatment. Duration of response was at least 6 months for 52.0% of the patients. 84.4% (54/64) of skin evaluable subjects had a decrease in skin tumor burden and 12.5% (8/64) saw complete clearing of skin disease. Pruritis was evaluated as an exploratory endpoint with 31.7% of patients demonstrating clinically significant pruritus improvement. Importantly, no cumulative toxicity was observed in patients receiving LYMPHIR.
LYMPHIR's safety profile is consistent with the known safety profile for denileukin diftitox. Across three studies of 119 CTCL patients receiving 9 μg dose of denileukin diftitox, the most common (≥20%) adverse reactions, including laboratory abnormalities, were increased transaminases, albumin decreased, nausea, edema, hemoglobin decreased, fatigue, musculoskeletal pain, rash, chills, constipation, pyrexia, and capillary leak syndrome (CLS).
About LYMPHIR™ (denileukin diftitox-cxdl):
LYMPHIR is a targeted immune therapy for r/r (R/R) CTCL indicated for use in Stage I-III disease after at least one prior systemic therapy. It is a recombinant fusion protein that combines the IL-2 receptor binding domain with diphtheria toxin fragments. The agent specifically binds to IL-2 receptors on the cell surface, causing diphtheria toxin fragments that have entered cells to inhibit protein synthesis. After uptake into the cell, the DT fragment is cleaved and the free DT fragments inhibit protein synthesis, resulting in cell death. Denileukin diftitox-cxdl demonstrated the ability to deplete immunosuppressive regulatory T lymphocytes (Tregs) and antitumor activity through a direct cytocidal action on IL-2R-expressing tumors.
In 2021, denileukin diftitox received regulatory approval in Japan for the treatment of CTCL and PTCL. Subsequently, in 2021, Citius acquired an exclusive license with rights to develop and commercialize LYMPHIR in all markets except for Japan and certain parts of Asia.
About Cutaneous T-cell Lymphoma:
Cutaneous T-cell lymphoma is a type of cutaneous non-Hodgkin lymphoma (NHL) that comes in a variety of forms and is the most common type of cutaneous lymphoma. In CTCL, T-cells, a type of lymphocyte that plays a role in the immune system, become cancerous and develop into skin lesions, leading to a decrease in the quality of life of patients with this disease due to severe pain and pruritus. Mycosis Fungoides (MF) and Sézary Syndrome (SS) comprise the majority of CTCL cases. Depending on the type of CTCL, the disease may progress slowly and can take anywhere from several years to upwards of ten to potentially reach tumor stage. However, once the disease reaches this stage, the cancer is highly malignant and can spread to the lymph nodes and internal organs, resulting in a poor prognosis. Given the duration of the disease, patients typically cycle through multiple agents to control disease progression. CTCL affects men twice as often as women and is typically first diagnosed in patients between the ages of 50 and 60 years of age. Other than allogeneic stem cell transplantation, for which only a small fraction of patients qualify, there is currently no curative therapy for advanced CTCL.
About Citius Pharmaceuticals, Inc.:
Citius Pharmaceuticals, Inc. is a biopharmaceutical company dedicated to the development and commercialization of first-in-class critical care products. In August 2024, the FDA approved LYMPHIR, a targeted immunotherapy for an initial indication in the treatment of cutaneous T-cell lymphoma. Citius Pharma's late-stage pipeline also includes Mino-Lok®, an antibiotic lock solution to salvage catheters in patients with catheter-related bloodstream infections, and CITI-002 (Halo-Lido), a topical formulation for the relief of hemorrhoids. A Pivotal Phase 3 Trial for Mino-Lok and a Phase 2b trial for Halo-Lido were completed in 2023. Mino-Lok met primary and secondary endpoints of its Phase 3 Trial. Citius is actively engaged with the FDA to outline next steps for both programs.
For more information, please visit www.citiuspharma.com.
