Japan has become the first country to develop lymphoma drugs through the Albert Einstein College of Medicine. This also marks the first time that Einstein licensed drugs have been approved for use in patients.
The new oral medication called Mundesine was designed by Einstein and synthesized at Victoria University in Wellington, New Zealand. It uses enzyme inhibition technology developed by Dr. Vern Schramm, Professor of Biochemistry at Einstein and Chairman Ruth Merns. It treats a group of invasive diseases of the type of lymphoma known as peripheral T-cell lymphoma (PTCL), in which the patient’s T cells have become cancerous, accounting for 10% to 15% of non-Hodgkin’s lymphoma. Although rare in the United States, PTCL is common in Asia, Africa, and the Caribbean, probably due to exposure to viruses such as Epstein-Barr virus and human T-cell leukemia virus.
Mundesine has been specifically approved for patients with PTCL recurrence (relapse) or refractory (treatment-resistant). To date, there are few effective treatments for these PTCL conditions. Patients with PTCL who relapse after chemotherapy currently have an average of only 6 months.
Dr. Schramm said: “This drug is a new class of drugs we have designed and the first drug that has been approved.” Patients with relapsed or refractory PTCL are considered to have incurable cancer. This approval is an important step in providing them with further treatment opportunities. This is our ultimate goal in biomedicine at Einstein, a new scientific discovery. Transformed to better make a living for the patient.
Dr. Schramm’s groundbreaking work involves creating molecules called transitional analogs that prevent the movement of key enzymes. His findings have led to powerful new strategies for the treatment of cancer, antibiotic resistance and autoimmune diseases. In the case of PTCL, Dr. Schramm’s goal is to inhibit the enzyme purine nucleoside phosphorylase (PNP). When PNP is blocked, PTCL cancer cells are killed.
In order to resist PNP, Dr. Schramm and his colleagues first explained the transient “transition state” of PNP–when the enzyme converts one chemical into another, it takes less than ten One hundredth of a second. The next step is to design a chemical that is very similar to the PNP transition state structure. The chemical, Fusindelin hydrochloride, was later formulated into the oral drug Mundesine. It strongly inhibits PNP by binding to PNP molecules in T cells of PTCL patients, rather than letting go.
Cancerous T cells that kill PNP allow chemicals called 2'-deoxyguanosine triphosphate to accumulate within them. This accumulation kills T cells by triggering apoptosis, a programmed cell death.
The approval of Japan’s Mundesine is based on 19 clinical trials. The drug was originally designed in Dr. Schramm’s laboratory with the support of the National Institutes of Health’s Institute of General Medicine. Its chemical synthesis was done in cooperation with Drs. Einstein licensed its PNP inhibitor product to BioCryst Pharmaceuticals Inc. ( 204983)