MELBOURNE, Australia,
July 23, 2012 /PRNewswire/ --
Key Points:
* Intravenous injection of Mesenchymal Precursor Cells (MPCs)
resulted in selective migration to inflamed joints and lymph nodes
in a sheep model of Rheumatoid Arthritis (RA)
* A single intravenous injection of allogeneic, or
"off-the-shelf", MPCs significantly reduced synovial tissue levels
of TNF-alpha, IL-6, and IL-17, and reduced mononuclear cell
infiltration
* Reduced cytokine and inflammatory cell levels were accompanied
by significant reduction in pathology severity scores and synovial
hyperplasia
* MPCs may have a mechanism of action that is unique from other
biological therapies by shutting down multiple cytokine pathways
simultaneously
* MPCs could be a safe, first line therapy to induce sustained
improvement of joint inflammation in RA
* Phase 2 clinical trial in RA expected to commence Q4 2012
* RA is the second clinical indication, after type 2 diabetes,
to be targeted using Mesoblast's intravenous product
formulation
Melbourne, Australia;
24 July 2012: Regenerative medicine
company Mesoblast Limited (ASX:MSB) today announced positive
results in a large animal model of Rheumatoid Arthritis (RA)
following a single intravenous injection of its proprietary
allogeneic, or "off-the-shelf", immunomodulatory adult Mesenchymal
Precursor Cells (MPCs).
Mesoblast Chief Executive Professor Silviu Itescu said that the results indicated
that the Company's immunomodulatory MPCs may have a mechanism of
action that is unique from other biological therapies by shutting
down multiple cytokine pathways simultaneously, and that this could
become a first line treatment with a superior and sustained benefit
on reducing inflammation and destruction of joints in people
suffering from severe RA.
RA is an autoimmune disease driven and perpetuated by
pro-inflammatory cytokines such as TNF-alpha, IL-6, and IL-17.
Treatments targeting any of these pathways alone are only
moderately effective in RA, need to be administered chronically,
and may cause unacceptable infectious adverse events. A single
intravenous injection of allogeneic MPCs in sheep with
collagen-induced arthritis concomitantly affected T cells,
monocytes/macrophages, and synoviocytes to simultaneously shut down
TNF-alpha, IL-6, and IL-17 cytokine pathways, and improve joint
pathology.
Severe joint synovial inflammation with cartilage loss and bony
erosions, characteristic of human RA, occurs in sheep injected with
collagen. In a pilot study, significant numbers of allogeneic MPCs
were detected in involved joints or lymph nodes of arthritic sheep
at 24 hours after a single intravenous injection, but not in normal
sheep, indicating that MPCs selectively migrate to sites of
immune-mediated inflammation.
A randomized, placebo-controlled study was next performed in 30
sheep with established collagen-induced arthritis, comparing a
single intravenous injection of allogeneic MPCs at one of three
doses (0.3, 1 and 2 million MPCs/kg) to saline. Thirty days later,
joint synovial tissues from arthritic sheep were examined. In
comparison with saline treated controls, synovial tissue from
arthritic sheep receiving a single intravenous injection of 2
million MPCs/kg showed 88% mean reduction in IL-6 levels (p=0.029),
83% mean reduction in TNF-alpha levels (p=0.049), 53% mean
reduction in IL-17 levels (p=0.005), and 52% mean reduction in
infiltrating monocytes/macrophages (p=0.009). MPC-treated animals
had a 31% mean reduction in histopathology severity scores compared
with controls (p=0.025). Intermediate effects were seen with 1
million MPCs/kg, and the lowest MPC dose was least effective.
These findings demonstrate that MPCs are immunoregulatory and
concomitantly suppress the activation and proliferation of T-cells,
monocytes, and synoviocytes seen in active Rheumatoid Arthritis.
Mechanistically, the data suggest that MPCs inhibit the Th17 CD4 T
cell subset, with the subsequent simultaneous reduction in the key
cytokines, IL-17, IL-6, and TNF-alpha. Mesoblast has an upcoming
scheduled meeting with the United States Food and Drug
Administration (FDA) to discuss its Phase 2 clinical program in
patients with RA. Subject to FDA clearance, the Company intends to
commence a randomized, placebo-controlled Phase 2 trial in the
fourth quarter of 2012. "Rheumatoid Arthritis represents the second
indication, after Type 2 diabetes, in a growing list of major
market segments that will be targeted by Mesoblast's intravenous
product formulation," Professor Itescu added.
About Rheumatoid Arthritis
Rheumatoid arthritis (RA) is a chronic systemic disease
characterized by progressive joint deformity and joint destruction
driven by synovial inflammation and hyperplasia in which cytokines
play central pathogenic roles. The prevalence of RA is estimated to
be 0.8% worldwide, with women twice as likely to develop the
disease as men. In the United
States, RA afflicts 1.3 million people. It is responsible
for 250,000 hospitalizations and 9 million physician visits each
year. According to Global Data, the RA 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 (CAGR) of 12.3%.
About Mesoblast
Mesoblast Limited (ASX: MSB) is a world leader in
commercialising biologic products for the broad field of
regenerative medicine. Mesoblast has the worldwide exclusive rights
for a series of patents and technologies developed over more than
10 years relating to the identification, extraction, culture and
uses of adult Mesenchymal Precursor Cells (MPCs).
www.mesoblast.com
For further information, please contact:
Julie Meldrum
Corporate Communications
Mesoblast Limited
T: + 61 (0) 3 9639 6036
E: julie.meldrum@mesoblast.com
SOURCE Mesoblast Ltd