Introduction to Lymphir and Its Approval

On August 8, 2024, Citius Pharmaceuticals announced that the U.S. Food and Drug Administration (FDA) had approved Lymphir (denileukin diftitox-cxdl), a novel immunotherapy for the treatment of relapsed or refractory cutaneous T-cell lymphoma (CTCL) after at least one prior systemic therapy. This approval marks a significant milestone for CTCL patients, offering a new treatment option for a rare and chronic cancer characterized by debilitating skin lesions and severe itching.

Lymphir is the first FDA-approved product for Citius Pharmaceuticals and the only CTCL therapy that targets the interleukin-2 (IL-2) receptor found on malignant T-cells and regulatory T-cells (Tregs). This unique mechanism of action provides a novel and non-cross-resistant treatment option for patients with Stage I-III CTCL, who often have limited treatment options.

Understanding Cutaneous T-cell Lymphoma (CTCL)

Cutaneous T-cell lymphoma is a type of non-Hodgkin lymphoma that primarily affects the skin. It is a rare and often debilitating chronic disease, with approximately 2,500-3,000 new cases diagnosed each year in the United States and an estimated 40,000 people living with the disease. CTCL manifests as skin lesions, which can cause severe itching, ulceration, and secondary infections, significantly impacting the quality of life of patients.

Patients with relapsed or refractory CTCL (r/r CTCL) typically cycle through several skin-directed therapies before the cancer becomes resistant or progressive. At this point, systemic agents are needed to achieve effective disease control. However, these treatments often come with dose-limiting toxicities, necessitating the need for new and effective therapies like Lymphir.

The Efficacy and Safety of Lymphir

The approval of Lymphir is based on the results from the Phase 3 Pivotal Study 302, an open-label, single-arm, multicenter trial involving patients with r/r Stage I to IV CTCL. The study included 69 patients who had previously received at least one systemic treatment, with a median of four prior anticancer therapies. Patients received Lymphir at a dose of 9 mcg/kg as an intravenous infusion daily from Day 1 through Day 5 of each 21-day cycle until disease progression or unacceptable toxicity.

The primary efficacy outcome measure was the Objective Response Rate (ORR), as assessed by an Independent Review Committee (IRC). The ORR was 36.2%, with 8.7% of patients achieving a Complete Response (CR). The median time to response was rapid at 1.41 months, with the majority of responders seeing results after 1-2 cycles of treatment. Importantly, 52% of patients had a duration of response of at least six months, and 84.4% of skin-evaluable subjects experienced a decrease in skin tumor burden.

Lymphir's safety profile is consistent with the known safety profile for denileukin diftitox. The most common adverse reactions (≥20%) included increased transaminases, decreased albumin, nausea, edema, decreased hemoglobin, fatigue, musculoskeletal pain, rash, chills, constipation, pyrexia, and capillary leak syndrome (CLS). Notably, no cumulative toxicity was observed in patients receiving Lymphir.

Addressing Safety Concerns and Monitoring

While Lymphir offers promising benefits, it is essential to address potential safety concerns and ensure proper monitoring. One of the significant risks associated with Lymphir is Capillary Leak Syndrome (CLS), which occurred in 27% of patients in the pooled population across three clinical trials. CLS can be life-threatening or fatal, characterized by symptoms such as hypotension, edema, and hypoalbuminemia. Regular assessment of patients for weight gain, new onset or worsening of edema, dyspnea, and hypotension is crucial. Serum albumin levels should be monitored before each cycle of therapy and more frequently as clinically indicated.

Another safety concern is visual impairment, which occurred in 9% of patients in the pooled population across three clinical trials. Symptoms included blurred vision and changes in visual acuity and color vision. Baseline ophthalmic examinations and regular monitoring are recommended, and Lymphir should be withheld or discontinued based on the severity of visual impairment.

Infusion-related reactions were reported in 69% of patients, with symptoms such as nausea, fatigue, chills, musculoskeletal pain, vomiting, fever, and arthralgia. Premedication for the first three cycles and close monitoring during infusions are advised to manage these reactions effectively.

Conclusion: A New Era for CTCL Treatment

The FDA approval of Lymphir represents a significant advancement in the treatment landscape for CTCL patients. With its unique IL-2 receptor-targeted mechanism, Lymphir offers a novel and effective option for patients with relapsed or refractory CTCL, providing rapid skin relief and control of symptomatic itching without cumulative toxicity. This approval brings new hope to patients suffering from this rare and chronic cancer, improving their quality of life and expanding the CTCL treatment market.

▍Dr. Francine Foss, Professor of Hematology and Director of the Multidisciplinary T-cell Lymphoma Program at Yale Cancer Center:

"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."

Citius Pharmaceuticals is dedicated to working closely with healthcare providers to ensure that all r/r CTCL patients have timely access to this important new therapy. The company is preparing to launch Lymphir in the U.S. market within the next five months, marking the beginning of a new era in CTCL treatment.

SOURCE Citius Pharmaceuticals, Inc.