Denileukin Diftitox to Expand Across EU for R/R Cutaneous T-Cell Lymphoma

Citius Oncology announced a distribution agreement with Uniphar, a Dublin-based international healthcare services company, to provide access to denileukin diftitox (Lymphir) across Western and Eastern Europe to patients with relapsed or refractory (R/R) cutaneous T-cell lymphoma (CTCL).¹

Denileukin diftitox is a targeted immunotherapy that was approved in the US in 2024.² The agreement with Uniphar marks Citius Oncology's third international partnership, following previous arrangements in Southern Europe, the Balkans, Türkiye, and the Middle East. Because denileukin diftitox is not yet approved for commercial use outside the US and Japan, it will be distributed in European territories exclusively through country-specific managed access programs.

Following the 2021 regulatory approval of denileukin diftitox in Japan for R/R CTCL and peripheral T-cell lymphoma, Citius secured an exclusive license that same year.¹ This agreement grants Citius the rights to develop and commercialize the treatment globally, excluding India, Japan, and specific Asian territories.

Denileukin diftitox is a recombinant fusion protein designed as a targeted immune therapy for specific stages of CTCL. The therapy combines the interleukin (IL)-2 receptor binding domain with diphtheria toxin (DT) fragments. Its function is two-fold:

• The agent binds to IL-2 receptors on the cell surface. Once internalized, the DT fragment is cleaved and inhibits protein synthesis, leading to cell death in IL-2R-expressing tumors.
• Denileukin diftitox has demonstrated the ability to deplete immunosuppressive regulatory T lymphocytes (Tregs).

“For example, these Tregs allow a better host patient's body to attack the tumor as well, and therefore it's quite unique with respect to Tregs,” said Myron Czuczman, MD, chief medical officer at Citius Pharmaceuticals, the developer of the agent, in an interview with Targeted Oncology in December 2025. “There's a lot of research being done in this field. We believe that, because we have such a short half-life of this agent, that, because it's transient, we get the activity intake and tumor activity.”

The phase 3 study (NCT01871727)³ that led to the approval of denileukin diftitox demonstrated efficacy and safety in patients with CTCL.²

The safety profile of denileukin diftitox is characterized most notably by capillary leak syndrome (CLS). Data from the pivotal clinical trial indicate that approximately 17% of patients experienced CLS, manifesting as peripheral edema, weight gain, and hemodynamic changes such as orthostatic hypotension. These adverse events (AEs) were predominantly grade 1 or 2 and remained manageable through routine monitoring and standard interventions.

One of the most clinically significant aspects of these toxicities is their temporal pattern and noncumulative nature. Unlike many traditional systemic therapies where toxicity risks increase over time, CLS associated with denileukin diftitox typically occurred during the first or second treatment cycle. The incidence and severity of these AEs decreased in subsequent cycles, allowing many patients to continue therapy without persistent complications.

Dose management strategies in the study demonstrated the feasibility of continuing treatment despite early-cycle toxicities. While 3 patients discontinued therapy based on clinical discretion and 2 required dose reductions, 6 patients successfully managed AEs through brief dose interruptions.

"This agreement with Uniphar builds on the momentum of our international expansion efforts and reflects our commitment to partnering with experienced organizations that have deep regional expertise and proven execution capabilities," said Leonard Mazur, chairman and CEO of Citius Oncology and Citius Pharmaceuticals, in a news release.¹ "As our third international distribution agreement, this partnership further strengthens our ability to responsibly expand access to [denileukin diftitox] for patients with limited treatment options, while continuing to lay the groundwork for long-term global growth."

REFERENCES

1.Citius Oncology expands international distribution of LYMPHIR to European Union through exclusive agreement with Uniphar. News release. Citius Oncology. Published February 11, 2026. Accessed February 17, 2026. https://tinyurl.com/47hh6h5b

2.Citius Pharmaceuticals receives FDA approval for LYMPHIR™ (denileukin diftitox-cxdl) immunotherapy for the treatment of adults with relapsed or refractory cutaneous T-cell lymphoma. News release. Citius Pharmaceuticals. August 8, 2024. Accessed February 17, 2026. https://tinyurl.com/48pj3x9z

3.A trial of E7777 in persistent and recurrent cutaneous T-cell lymphoma. ClinicalTrials.gov. Updated November 13, 2024. Accessed February 17, 2026. https://clinicaltrials.gov/study/NCT01871727