New FDA Approval: LYMPHIR™(denileukin diftitox-cxdl)
The U.S Food and Drug Administration recently approved Lymphir (denileukin diftitox-cxdl), an IL2-receptor-directed cytotoxin indicated for the treatment of adult patients with relapsed or refractory Stage I-III cutaneous T-cell lymphoma after at least one prior systemic therapy.
Read InpharmD's summary below:
| Drug Name |
LYMPHIR™(denileukin diftitox-cxdl) |
| Active Ingredient |
denileukin diftitox-cxdl |
| Date of Approval |
August 7, 2024 |
| Manufacturer |
Citius Pharmaceuticals, Inc. |
| Approval Pathways and Indications |
Approval Pathway: BLA
Indication: LYMPHIR™ is an IL2-receptor-directed cytotoxin indicated for the treatment of adult patients with relapsed or refractory Stage I-III cutaneous T-cell lymphoma (CTCL) after at least one prior systemic therapy |
| Therapeutic Class |
Immunotherapy |
| Formulation |
For injection: 300 mcg lyophilized cake in a single-dose vial |
| MoA |
LYMPHIR™ contains denileukin diftitox-cxdl, a recombinant engineered fusion protein that combines interleukin-2 and diphtheria toxin. The agent specifically binds to IL2 receptors on the cell surface, causing diphtheria toxin fragments that have entered cells to inhibit protein synthesis. Its unique mechanism of action targets both malignant T-cells and immunosuppressive regulatory T-cells (Tregs). Transiently eliminating Tregs has the potential of unleashing potent immune responses by the patient's immune system against their tumors. |
| Dosing and Administration |
Recommended Dosage: 9 mcg/kg/day (actual body weight) administered as an intravenous infusion over 60 minutes on Days 1 through 5 of each 21-day treatment cycle. Continue until disease progression or unacceptable toxicity.
Pre-Treatment Assessment: Evaluate liver and kidney function before each cycle; dosage may be adjusted based on results.
Premedication: Administer at least 30 minutes before infusion for the first 3 cycles:
Anti-fever medicine (e.g., acetaminophen)
Antihistamine (e.g., diphenhydramine)
Anti-nausea medication
Infuse 250 mL to 500 mL of 0.9% sodium chloride intravenously.
Infusion Reactions: For Grade 2 or higher reactions, premedicate with systemic steroids (e.g., dexamethasone 4 mg) via slow intravenous push at least 30 minutes before subsequent infusions for a minimum of 3 cycles. |
| Administered by self or by HCP |
Administered by HCP |
| Place in Therapy |
LYMPHIR™ is a purified reformulation of denileukin diftitox, a cancer immunotherapy first approved in 1999 under the brand name Ontak for the treatment of persistent or recurrent CTCL, a type of non-Hodgkin lymphoma. It is caused when the T-cells become cancerous and develop into skin lesions. Ontak was marketed in the U.S. from 1999 to 2014, when it was voluntarily withdrawn from the market. LYMPHIR™ is thought to feature greater purity and bioactivity compared to the original formulation.
The product label for LYMPHIR™ carries a Boxed Warning for Capillary leak syndrome (CLS). Warnings and precautions associated with LYMPHIR™ include visual impairment, infusion-related reactions, hepatotoxicity, and fetal harm. As part of the approval for LYMPHIR™, the FDA has advised that a further clinical trial is required to characterize the known serious risk of visual impairment. |
| Expected Market Launch Date |
Within the next 5 months |
| New Molecular Entity (NME) or Existing Formulation |
Existing Formulation |
| Expected Cost |
Data Unavailable |
| Product Discontinuation |
N/A |
| Clinical Trials |
LYMPHIR™ has been evaluated in three pivotal clinical studies involving adult patients with relapsed or refractory Stage I-III CTCL who had previously undergone at least one systemic therapy. The studies aimed to assess the efficacy and safety of LYMPHIR™ administered at a dose of 9 mcg/kg/day over 5 consecutive days every 21 days until disease progression or unacceptable toxicity.
The trials were open-label, single-arm studies. The primary endpoint was the objective response rate (ORR), which included complete response (CR) and partial response rates. Secondary endpoints included duration of response, progression-free survival, and overall survival.
LYMPHIR™ demonstrated an ORR of 36% and a CR of 8.7%. The median time to response was 1.41 months and the duration of response was at least 6 months for 52% of patients. 84% of patients had a decrease in skin tumor burden and 12.5% saw complete clearing of skin disease. |
| Sources |
PR Newswire. Citius Pharmaceuticals Receives FDA Approval for LYMPHIR (Denileukin Diftitox-cxdl) Immunotherapy for the Treatment of Adults with Relapsed or Refractory Cutaneous T-Cell Lymphoma. Available at: https://www.prnewswire.com/news-releases/citius-pharmaceuticals-receives-fda-approval-for-lymphir-denileukin-diftitox-cxdl-immunotherapy-for-the-treatment-of-adults-with-relapsed-or-refractory-cutaneous-t-cell-lymphoma-302217630.html. Accessed August 13, 2024.
Drugs.com. LYMPHIR Approval History. Available at: https://www.drugs.com/history/lymphir.html. Accessed August 13, 2024.
U.S. Food and Drug Administration. LYMPHIR (denileukin diftitox-cxdl) Label. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/761312s000lbl.pdf. Accessed August 13, 2024. |
Share