The potential of this candidate is made all the more urgent as increasing numbers of patients are becoming unresponsive to Disease-Modifying-Anti-Arthritis Drugs (DMARDS), the first line therapies for RA.
Biological agents such as the tumour necrosis factor (TNF alpha) blockers Enbrel, Remicade and Humira are now established treatments for patients failing DMARDS. However, up to 40 per cent of patients fail to respond to these agents or respond until neutralizing antibodies develop as a consequence of repeated dosing.
The antibody, which has been developed by researchers at the Ludwig Institute for Cancer Research (LICR), Australia, have shown that in animal studies, blocking the function of a particular protein target with the neutralizing antibody appears to prevent the induction of arthritis. More significantly, treatment of ongoing disease with the antibody halts the disease's progression.
Geoff Yarranton, Chief Executive Officer at KaloBios told DrugResearcher.com: "The antibody interferes with mechanisms that mobilize immune cells from the bone marrow and send these cells to the joints. In addition, the antibody stops the activation and further division of these cells in the joint where they cause damage to the bone and cartilage."
"The KaloBios antibody falls into the class of biologic response modifiers but does not target TNF or interleukin 1(IL-1 - protein produced naturally by our bodies to stimulate our immune systems). Biologic response modifiers slow tissue and joint damage. Our agent will have an impact on a broader range of disease mechanisms producing responses in non-responders."
RA is an autoimmune disease that leads to painful inflammation and ultimately destruction of bone joints. It affects 2.1 million Americans, of which 1.5 million are women compared to 600,000 men. Onset is usually in middle age, appears more frequently in older people, but also affects children and young adults.
Musculoskeletal conditions such as rheumatoid arthritis cost the U.S. economy nearly $86.2 billion (€70.9 billion) per year in medical care and indirect expenses such as lost wages and production.
KaloBios plans to enter the first generation antibody into human clinical trials by the second half of 2005. Yarranton also said that KaloBios intends to develop this novel therapeutic to at least the end of Phase II clinical trials before seeking a partner.