Mesoblast (ASX: MSB) has received clearance from the U.S. Food and Drug Administration to begin a phase two trial evaluating a single intravenous infusion of allogeneic, or “off-the-shelf”, Mesenchymal Precursor Cells (MPCs) for the treatment of active rheumatoid arthritis.
This is the first in a series of programs designed to establish the credentials of the company’s intravenous product formulation for a broad-based spectrum of inflammatory and immunologic conditions.
Rheumatoid arthritis is an autoimmune disease caused by aberrant activation of multiple immune pathways involving both monocytes and T cells, ultimately resulting in joint destruction.
Existing biologic treatments target only single immune pathways, resulting in incomplete responses, need for chronic administration, and potentially unacceptable infectious adverse events.
In contrast, Mesoblast's MPCs have been shown in preclinical studies to have a broad immuno-modulatory mechanism of action, simultaneously inhibiting T cells and monocytes involved in inflammation and autoimmunity.
The broader effects of Mesoblast's MPCs on multiple immune pathways suggest that they may be particularly useful agents for reducing the inflammation and permanent joint damage associated with progression of rheumatoid arthritis.
Mesoblast’s randomised, double-blind placebo-controlled trial is expected to begin during the June quarter 2013, and will recruit patients across multiple sites in the U.S. States and Australia.
The trial will compare the effects of a single intravenous infusion of allogeneic MPCs dosed at 1 or 2 million cells per kilogram compared with placebo in 48 patients who have had an incomplete or inadequate response to a biologic inhibitor of the TNF-alpha pathway for active rheumatoid arthritis.
Safety and effectiveness of the MPC therapy will be assessed at multiple time points with the primary endpoints defined as three months.
A randomised, placebo-controlled study in 30 sheep with collagen-induced arthritis, a model that manifests joint damage characteristic of human rheumatoid arthritis, treatment with Mesoblast’s MPCs showed that the MPCs can concurrently inhibit both Th17 T cells and pro-inflammatory monocytes, and improve synovial tissue pathology.
This provides a rationale for their potential use as both a first-line biologic treatment in those not responding to conventional anti-rheumatic agents and in patients with incomplete responses to biologic inhibitors of the TNF-alpha pathway alone.
Large therapeutics market
The rheumatoid arthritis therapeutics market was valued at $10.3 billion globally in 2010, and has doubled over a four-year period after growing at a compound annual growth rate of 12.3%.
The prevalence of the disease is estimated to be 0.8% worldwide, with women twice as likely to develop the disease as men.
In the U.S. alone, rheumatoid arthritis afflicts 1.3 million people. It is responsible for 250,000 hospitalisations and 9 million physician visits each year.
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