Experimental drug PLX5622 has been shown in preclinical arthritis models to reduce inflammation, reduce cartilage damage, and prevent bone resorption.
The experimental drug PLX5622, which has been shown in preclinical arthritis models to reduce inflammation, reduce cartilage damage, and prevent bone resorption, began dosing for the first of two phase 1 clinical trials.
The drug is an oral and highly selective Fms inhibitor manufactured by Plexxikin, Inc. Fms-related inflammatory mediators and cells, including macrophages, osteoclasts and T-cells, have been validated as key players in RA, other autoimmune diseases, and osteoarthritis.
The initial phase 1 trial is a single-ascending dose study in 32 healthy volunteers. The second trial is a multiple-ascending dose study in 32 RA patients that will begin once the first cohort of healthy volunteers has been cleared for safety, with continued enrollment in a staggered fashion relative to the single-ascending dose study.
"PLX5622 is an important and differentiated candidate among Plexxikon's portfolio of Fms inhibitors that are being developed for multiple indications, and yet another first-in-class compound from Plexxikon," K. Peter Hirth, CEO of Plexxikon, said in a press release. "By targeting key drivers of the inflammatory process, we are hopeful that PLX5622 may provide relief to patients with rheumatoid arthritis and other autoimmune disorders, with the convenience of a pill."
PLX5622 is designed to provide therapeutic benefit by modulating macrophage proliferation, inhibiting production of pro-inflammatory cytokines, and preventing the formation of osteoclasts. Osteoclasts bone resorptive activity is responsible for excessive bone destruction in several diseases.
In preclinical models of arthritis, PLX5622 demonstrated substantial disease suppression, including in advanced models of collagen-induced arthritis. PLX5622 significantly improved grip strength and clinical scores, as well as improved knee joint range-of-motion scores.
Plexxikon is completing a phase 1 trial with PLX3397, another Plexxikon Fms inhibitor that selectively targets Fms, Kit, and the Flt-3-ITD mutation. This study has provided validation of Fms-specific biomarkers, which will be directly applicable to the development of PLX5622 in defining a dose response. The company plans to initiate several proof-of-concept clinical trials with PLX3397, including in Hodgkin lymphoma, glioblastoma, acute myelogenous leukemia (AML) and metastatic breast cancer in 2011.
According to its website, Plexxikon focuses on discovering and developing novel, small molecule pharmaceuticals. The company has manufactured treatments in the therapeutic areas, including cardio-renal disease, CNS, inflammation, metabolic disease and oncology.
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