Cutaneous T-cell lymphomas (CTCL) are a subset of extranodal non-Hodgkin lymphoma (NHL) that come in a variety of forms mainly localized to the skin. In patients with CTCL, T-cells become cancerous and initially develop into skin lesions with potential involvement of the nodes, blood, and viscera. CTCL is often associated with a decrease in the quality of life secondary to pruritus (severe itching).
The most common types of CTCL are mycosis fungoides (MF) and primary cutaneous CD30+ anaplastic large cell lymphoma (pcALCL), jointly representing an estimated 80–85% of all CTCL. Sézary Syndrome (SS), a very rare subtype (~2–5% of CTCL) characterized by diffuse inflammatory, often exfoliative, erythroderma and by leukemic and nodal involvement, displays a significant degree of clinical and biological overlap with MF and has long been considered a clinical variant of MF, although recent evidence suggests that it may be a separate entity. The rest is represented by extremely rare, generally more aggressive subtypes. In light of the overlap between MF and SS, and considering that many of the systemic therapy options for the two neoplasms are the same, some consider the treatment approach to MF and SS as if they were a single disease entity (MF/SS). However, some of the drugs currently in use, or in development, for MF/SS appear to be more effective in clearing different anatomical compartments (skin versus blood, for example) and therefore have differential efficacy in MF and SS. Depending on the type of CTCL, the disease may progress slowly, but once the skin disease becomes resistant to skin-directed therapies and/or the disease spreads inside the body it is considered highly malignant with a poor prognosis and requires systemic therapy.
A Rare Disease
Based on Surveillance Epidemiology and End Results (SEER) data from 2001–2007, the estimated incidence rate of MF/SS in the U.S. is 0.5/100,000 or about 2,500–3,000 new cases per year representing about 25% of all T-cell lymphomas.
We estimate that there are 30,000 – 40,000 patients living with CTCL in the U.S. with approximately 16,000 – 20,000 having mycosis fungoides. Of those, we believe the addressable population for I/ONTAK will be the approximately 10,000 patients with later stage, relapsed or refractory CTCL who require systemic therapy, resulting in an estimated addressable U.S. market of approximately $300,000,000. LYMPHIRTM has been granted Orphan Drug Designation by the U.S. FDA.
Disease Treatment
Given the duration of the disease, patients typically cycle through multiple systemic 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 cure for advanced CTCL.
There is no single standard-of-care for the treatment of CTCL, with only a few FDA-approved targeted therapies for patients with advanced CTCL. Existing targeted therapies are often poorly tolerated or have limited efficacy and may be discontinued due to toxicity, adverse events, or the development of resistance to treatment. As such, we expect LYMPHIRTM, with its unique non-cross-resistant mechanism-of-action and ONTAK’s prior well documented safety and efficacy profile, to be an important option for patients and their physicians in the management of this disease.
Potential Therapy for Additional Indications
LYMPHIRTM may also have substantial upside as a therapy for peripheral T-cell lymphoma (PTCL) and possibly in combination with check-point inhibitors such as pembrolizumab or CAR T-cell based therapy (e.g. KYMRIAH®) based on its ability to transiently eradicate Tregs from the suppressive tumor microenvironment.