Human Genome Sciences, Inc. (HGSI), a company with the mission to treat and cure disease by bringing new gene-based drugs to patients, reported that the company scientists presented at the 38th Annual Meeting of the American Society of Clinical Oncology in Orlando, Florida, some of the preclinical data that support the successful filing of its Investigational New Drug application to the U. S. Food and Drug Administration (FDA) to begin clinical development of LymphoRad 131 for use in the treatment of B-cell cancers (Abstract #391).
On May 14, 2002, Human Genome Sciences announced that LymphoRad had been cleared by the FDA for Phase 1 clinical studies. The first trial, as announced, will be done in patients with multiple myeloma.
B-cell tumors such as multiple myeloma and non-Hodgkin lymphomas are known to be highly susceptible to lethal effects of radiation. Preclinical studies show that LymphoRad, a radioiodinated form of B lymphocyte stimulator (BLyS), binds to receptors found only on B-cells and B-cell tumors, delivering low doses of radiation that cause cell death. LymphoRad has the potential to treat a broad range of B-cell tumors, including multiple myeloma, chronic lymphocytic leukemia, and non-Hodgkin lymphomas such as large B-cell lymphomas, follicular B-cell lymphomas, and Burkitt's lymphoma.
The Multiple Myeloma Research Foundation estimates that over 14,000 new cases of multiple myeloma are diagnosed each year in the United States3. It is estimated that 105,000 people in the U.S., Europe and Japan have multiple myeloma4. Multiple myeloma is the second most prevalent blood cancer and is approximately twice as prevalent in men as in women. Multiple myeloma is also among the ten leading causes of death in African Americans.
The first set of experiments described at the American Society of Clinical Oncology's Annual Meeting [Abstract #39: "LymphoRad131 (Radiolabeled BLyS Protein) Inhibits Neoplastic B-Cell Growth In Vivo"] were designed to measure the distribution of LymphoRad in normal mice and in mice bearing B-cell tumors. These studies show that LymphoRad targets tissues that contain B-cells and the B-cell tumors. In normal mice, LymphoRad is found predominantly in the spleen and lymph nodes, and only at very low levels in the kidney and liver. In tumor-bearing mice, LymphoRad concentrates in the B-cell tumors. These experiments suggest that LymphoRad is likely to be a targeted, effective therapy for B-cell tumors.
The second set of experiments examines the effects of LymphoRad on blood cells. Treatment with LymphoRad has little effect on the number of circulating monocytes, neutrophils or red blood cells. Transient depletion of platelet counts was noted in the treated animals. Examination of the bone marrow of treated mice revealed transient depression of the total number of cells, early hematopoietic precursor cells and of pro- and pre- B-cell populations. Mature B-cell populations were profoundly depleted but later regained about one third of normal mature B-cell numbers. These studies suggest that LymphoRad, although mildly myelosuppressive, should selectively target normal B-cells and B-cell tumors.
The next series of experiments were designed to measure the effect of LymphoRad on the growth of B-cell tumors in mice and the survival of mice bearing B-cell tumors. These studies show that a single dose of LymphoRad, given after the establishment of B-cell tumors, limits the growth and lethal effects of the tumors. In one model, the size of established tumors was reduced over 15-fold by a single injection of the drug. LymphoRad was effective in reducing the growth rate and size of B-cell tumors studied in mice. In a second model, the single injection of LymphoRad was shown to be capable of significantly extending the life span of mice bearing a splenic lymphoma. These results support the potential of LymphoRad as a drug to treat B-cell tumors of man.
LymphoRad will be manufactured in accordance with the FDA's Good Manufacturing Practice (GMP) guidelines. The targeting protein, BLyS, will be manufactured at Human Genome Sciences in Rockville, Md. LymphoRad will be manufactured at a GMP manufacturing facility at MDS Nordion in Ottawa, Canada. Construction of this new facility has been completed and validation is currently underway. MDS Nordion will use a process it developed for Human Genome Sciences that covalently binds the radioactive isotope iodine-131 to the BLyS protein. Human Genome Sciences expects to begin enrollment of LymphoRad clinical studies during the second half of 2002 following validation of the new GMP manufacturing plant.