The U.S. Food and Drug Administration (FDA) has granted orphan drug designation (ODD) to investigational drug tinostamustine, a potentially first-in-class alkylating deacetylase inhibiting molecule being studied in early phase clinical trials, for the treatment of T-cell prolymphocytic leukemia (T-PLL).

T-PLL is an extremely rare and aggressive T-cell leukemia that is characterized by out of control growth of mature T-cells. There are very limited effective treatment options for T-PLL. The disease typically progresses rapidly and does not respond well to standard multi-agent chemotherapy. T-PLL affects about 2% of all patients with mature lymphocytic leukemias.  It is characterized by the out of control growth of mature T-cells (T-lymphocytes). T-cells are a type of white blood cell that protects the body from infections. The majority of patients present with hepatosplenomegaly and generalized lymphadenopathy, with skin infiltration, anemia and thrombocytopenia often seen. T-PLL affects older adults with a median age at diagnosis of 61 years, and it is more common in men than in women.

“This orphan drug designation represents an important step not just for Imbrium and the development of tinostamustine, but also for the patients suffering from T-PLL who do not currently have sufficient treatment options,” said Richard Fanelli, PhD, head of Regulatory Affairs, Imbrium Therapeutics.

The FDA grants ODD status to medicines intended for the treatment, diagnosis or prevention of rare diseases or disorders that affect fewer than 200,000 people in the United States. Orphan drug designation is intended to facilitate drug development for rare diseases and may provide certain incentives to drug developers. T-PLL is an extremely rare and typically aggressive blood cancer. It is so rare that healthcare professionals may only see one case of T-PLL every five to 10 years. Due to its rarity, T-PLL can be misdiagnosed, resulting in poor patient outcomes with a median survival of around one year. There is no guarantee that tinostamustine, an investigational agent, will successfully complete clinical development or gain FDA approval.

To be eligible for trial enrollment, patients must have had a diagnosis of a lymphoid malignancy and had no other available therapies for treatment. Patients with multiple myeloma, Hodgkin lymphoma, cutaneous T-cell lymphoma, peripheral T-cell lymphoma, and T-PLL were allowed to receive tinostamustine in phase 1. The dose-expansion phase will determine the overall response rate, duration or response, and safety in all 5 patient cohorts.

Preclinical experiments have also shown tinostamustine’s activity in solid malignancies such as small cell lung cancer, soft tissue sarcoma, triple-negative breast cancer, and ovarian cancer. Clinical trials are actively recruiting.