Forodesine HCL (PNP Inhibitor)

Purine Nucleoside Phosphorylase (PNP) Inhibitor Program (528 KB)

Forodesine HCL, is a transition-state analog inhibitor of the target enzyme purine nucleoside phosphorylase (“PNP”) designed to treat T-lymphocyte mediated disorders. An oral formulation of the compound is currently being studied in a pivotal trial for patients with cutaneous T-cell lymphoma. This trial is being conducted under a Special Protocol Assessment (“SPA”) agreed to with the U.S. Food and Drug Administration (“FDA”). Read the full press release here:

BioCryst Initiates Enrollment in Pivotal Trial of Forodesine HCL in Patients with CTCL

Additionally, an oral formulation of forodesine HCL is currently being studied in a Phase II trial for patients with chronic lymphocytic leukemia (“CLL”).

Forodesine HCL has been granted Orphan Drug status by the FDA for three indications: T-cell non-Hodgkin's lymphoma, including CTCL; CLL and related leukemias including T-cell prolymphocytic leukemia, adult T-cell leukemia, and hairy cell leukemia; and for treatment of B-ALL. The FDA has also granted “fast track” status to the development of forodesine HCL for the treatment of relapsed or refractory T-cell leukemia.

In February 2006, BioCryst announced an exclusive licensing agreement with Mundipharma International Holdings Limited (“Mundipharma”) to develop and commercialize forodesine HCL for use in the treatment of oncology in markets across Europe, Asia, Australia and certain neighboring countries. Read the full press release here:

BioCryst and Mundipharma Collaborate on Development of Forodesine HCL

T-cell Related Diseases

The human immune system employs specialized cells, including T-cells, to control infection by recognizing and attacking disease-causing viruses, bacteria and parasites. T-cells are an essential part of the body's immune system that serve a dual purpose to both orchestrate and participate in the body's immune response. For the most part, this system works flawlessly to protect the body. However, when T-cells multiply uncontrollably, T-cell proliferative diseases, such as T-cell cancers, can occur.

The link between T-cell proliferation and the purine nucleoside phosphorylase, or PNP, enzyme was first discovered approximately twenty-five years ago when a patient, who was genetically deficient in PNP, exhibited limited T-cell activity, but reasonably normal activity of other immune functions. In other patients lacking PNP activity, the T-cell population was selectively depleted; however, B-cell function tended to be normal. Based on these findings and the results of cell culture studies, inhibiting PNP appears to produce selective suppression of T-cells without significantly impairing the function of other cells.

Acute Lymphoblastic Leukemia

The most common form of leukemia in children is acute lymphoblastic leukemia (“ALL”). According to the American Cancer Society, 3,930 new cases (adult and children combined) will be diagnosed in the United States in 2006 (T-cell and Bcell). ALL results from an acquired injury to the DNA of a single cell in the bone marrow.

T-cell Lymphoma

Lymphoma is a general term for a group of cancers that originate in the lymphatic system. About 58,870 Americans will be diagnosed with a non-Hodgkin's lymphoma in 2006 and approximately 15% of these will be considered T-cell lymphomas. T-cell lymphoma results when a T-lymphocyte (a type of white blood cell) undergoes a malignant change and begins to multiply, eventually crowding out healthy cells and creating tumors, which enlarge the lymph nodes and invade other sites in the body. CTCL is a primary skin neoplasm and accounts for nearly 50% of all T-cell malignancies.

T-cell Mediated Autoimmune Diseases

There are more than 80 clinically distinct autoimmune diseases such as psoriasis, rheumatoid arthritis, multiple sclerosis, and Crohn's disease, which appear to have activated T-cells as a major part of their pathogenesis. These diseases occur when the immune system attacks the body's own cells rather than invading microorganisms. Therefore, inhibition and/or elimination of activated T-cells could have a beneficial effect on these diseases.

Transplant Rejection

The greatest threat to transplant patients is rejection of the transplanted organ by the body's own immune system. For this reason, transplant recipients must take drugs to suppress the immune response and prevent rejection usually for the rest of their lives. A regimen combining several drugs is usually given and this treatment has to be continued indefinitely. For kidney transplant recipients, rejection of the new kidney by the patient's immune system can lead to loss of the transplanted organ and a return to dialysis. For heart, lung and liver transplant patients, loss of the transplanted organ presents an immediate threat to life.

Forodesine HCL

(PNP Inhibitor)

More research information

Forodesine HCL (PNP Inhibitor)

T-cell Related Diseases