From the Archives: Summer 2005 Issue of Lupus Now Magazine
Healthcare Professionals Section
Drug Spotlight: Epratuzumab
Immunomedics’ Epratuzumab On FDA Fast Track For Lupus Therapy
Immunomedics, Inc. based in Morris Plains, NJ, announced in January that the U.S. Food and Drug Administration (FDA) had granted its drug candidate—epratuzumab—Fast Track Product designation for the treatment of patients with moderate to severe systemic lupus erythematosus. Epratuzumab is a humanized anti-CD22 monoclonal antibody that is currently under development for the treatment of various autoimmune diseases.
The immune system is made up of many types of cells; three of these are the B lymphocytes, commonly called the B cells, the T lymphocytes (the T cells), and the phagocytes, or scavenger cells. These three groups of cells are the “soldiers” of the immune system, and together they are designed to protect the body from foreign invaders—germs, bacteria, viruses, and fungi—called antigens. Researchers today are evaluating newer biological therapies that use the patient’s own immune system to fight diseases such as cancer and lupus. One of these new therapies involves monoclonal antibodies. Monoclonal antibodies are immune proteins that can be modified and produced through laboratory processes. They are developed to be able to bind to very specific components of antigens. Because specific proteins can be found on different types of cells, monoclonal antibodies can be designed to target individual types of cells in the body.
In patients with lupus there is frequent B cell hyperactivity and production of antibody targeting their own cells and tissues. More than one therapeutic strategy to modulate or delete all or some of the B lymphocytes is currently being explored. Epratuzumab has been designed to bind to an antigen called the CD22 antigen, which is found on B lymphocytes. This binding action produces several responses within the cell and the body, which ultimately provide mild B cell depletion and a diminishing of B cell function.
Thomas Eckhardt, Dr.Sc.Nat, Vice President of Regulatory Affairs and Quality Assurance/Quality Control at Immunomedics, explains, "The improved understanding of the immunological aspects of lupus enables the use of monoclonal antibodies that target critical components of the immune system involved in the disease. This may offer the prospect of having more efficacious and less toxic medicines available to control lupus."
A Phase II study completed in 2004 in Europe showed that epratuzumab might have the potential to lower lupus disease activity in various organs. While this was a very small preliminary study (and therefore not conclusive), the European study began to provide some helpful information about the safety, tolerance, and immunogenicity of the treatment (i.e. the potential of antibodies being made against the drug itself, which is always a concern when testing new treatments for lupus). The patients who participated in this early study had moderately active lupus disease, and were receiving only maintenance doses of other therapeutic agents. Fourteen patients evaluated after receiving four 30-minute infusions of epratuzumab every other week showed no infusion-related reactions or serious adverse events that were attributed to the drug, and there was no evidence of antibodies evoked against the drug, although many more patients would need to be tested to confirm these results.
According to Ivan D. Horak, M.D., Immunomedics’ executive vice president of Research and Development, and chief scientific officer, “Epratuzumab seems to demonstrate a reduction in disease activity in lupus patients without a drastic drop in their circulating B lymphocytes, thus perhaps reducing their risk of infection. This suggests to us that this CD22-targeting molecule may work by modulating B cell function, as contrasted by other anti-B cell antibodies that appear to require depletion of B cells.”
Phase III trials of epratuzumab in for the treatment of lupus are now underway.
Immunomedics is a biopharmaceutical company focused on the development of monoclonal, antibody-based products for the targeted treatment of cancer, autoimmune and other serious diseases. The company has developed a number of advanced proprietary technologies for the creation of humanized antibodies that can be used either alone in unlabeled or “naked” form, or conjugated with radioactive isotopes, chemotherapeutics or toxins, in each case to create highly targeted agents.