Regenerative medicine company Mesoblast Limited (ASX:MSB;
USOTC:MBLTY) today announced positive 12 month outcome results from
the 100-patient Phase 2 clinical trial of its proprietary
allogeneic, or "off-the-shelf", Mesenchymal Precursor Cells (MPCs)
in patients with chronic moderate to severe discogenic low back
pain.
The results showed that a single injection of MPCs into
degenerating intervertebral discs reduced low back pain and
improved function for at least 12 months. When compared with
controls, MPC-treated patients used less opioids for pain relief,
had greater radiographically-determined disc stability, and
underwent less additional surgical and non-surgical treatment
interventions. MPC treatments also appeared to be well tolerated
during the study.
Mesoblast Chief Executive Silviu Itescu said: "We are very
pleased that in a trial primarily designed to assess the safety of
Mesoblast's cells for intervertebral disc repair, we have seen
strong indications of sustained efficacy across a broad number of
clinical and radiographic parameters after a single intra-disc
injection. On the basis of these positive results, Mesoblast plans
to meet shortly with regulatory authorities in major jurisdictions,
including the United States Food and Drug Administration, to
discuss product registration trials for the potential treatment of
disc degeneration."
Dr Hyun Bae, Clinical investigator and Medical Director,
Director of Education, Cedars-Sinai Spine Center, Cedars-Sinai
Medical Center, Los Angeles, and Medical Director of Spine
Institute, Santa Monica, USA, said: "We are very excited by these
results. This is compelling evidence that Mesoblast's stem cell
technology has the potential to change the treatment of spinal
disease from focusing on surgical reconstruction to biologic
regeneration. Physicians and patients are seeking access to a new
modality to treat patients with this highly debilitating disease
for whom there are limited options. We hope that these outcomes
will be replicated in a pivotal trial."
The results of the Phase 2 clinical trial build on and extend
previously reported preclinical studies which showed that
Mesoblast's highly purified and immunoselected MPCs were able to
increase proteoglycan content and improve disc structure in an
experimental ovine model of disc degeneration.
Mesoblast's Phase 2 clinical trial enrolled 100 patients with
moderate to severe low back pain persisting for more than 6 months
and caused by early disc degeneration (less than 30% disc height
loss, 83% below Pfirrmann Grade 5 by MRI). Patients were enrolled
across 13 sites in the United States and Australia and randomized
to receive direct intra-disc injection of saline (n equals 20),
hyaluronic acid (HA, n equals 20), 6 million allogeneic MPCs in
hyaluronic acid carrier (6M, n equals 30) or 18 million allogeneic
MPCs in hyaluronic acid carrier (18M, n equals 30). Patients
underwent the outpatient injection for a single painful degenerated
lumbar level and are being evaluated for safety and efficacy over a
total of 36 months to evaluate long-term treatment effects.
Key findings at 12 months were:
-- Improvement in chronic low back pain
(a) Reduction in mean pain score: While mean pain scores, as
measured by a Visual Analog Scale (VAS), were similar for all four
groups at baseline (67 points for saline, 72 points for HA, 70
points for 6M MPC, 72 points for 18M MPC), at 12 months MPC
treatment resulted in significantly greater pain reduction than was
seen in controls. Mean pain reduction at 12 months was 40 points
for the 18M MPC group, 37 points for the 6M MPC group, 27 points
for HA controls, and 27 points for saline controls (p equals 0.046
and p equals 0.11, respectively, for 18M MPC and 6M MPC vs pooled
controls).
(b) Increased proportion of patients achieving greater than 50%
reduction in pain score: Achieving more than 50% reduction in low
back pain at 12 months is considered by many patients and
physicians as a key target. A significantly greater proportion of
MPC treated patients achieved at least a 50% reduction in low back
pain at 12 months, as measured by VAS, than controls (6M MPC 69%,
18M MPC 62%, HA 35%, saline 31%, p equals 0.036 between groups).
Both MPC dose groups had a significantly greater proportion of
patients with 50% or more reduction in back pain from baseline
compared to the pooled controls (6M, p equals 0.009, 18M p equals
0.038).
(c) Increased proportion of patients achieving minimal residual
back pain: Minimal residual back pain at 12 months was considered
if the VAS score was less than or equal 20. A significantly greater
proportion of MPC treated patients achieved minimal residual back
pain at 12 months than controls (6M group 52%, 18M group 42%,
pooled controls 18%, p equals 0.01 and p equals 0.05,
respectively).
(d) Reduced opioid use for pain relief: At 12 months, mean daily
use of opioid medications for back pain was reduced by as much as
42% in the 18M MPC group compared with the saline control group (p
equals 0.17). Mean opioid use was 1.00 tablet/day saline group,
0.94 tablet/day HA group, 0.77 tablet/day 6M MPC group, and 0.58
tablet/day 18 MPC group. Mean opioid use was also over two-fold
higher in saline and HA controls achieving greater than or equal to
50% reduction in pain score than in MPC treated patients,
indicating that pain reduction in the controls may have been due to
high opioid intake rather than to any biologic effect (mean opioid
use 1.3 and 1.2 tablets/day in saline and HA controls compared with
0.7 and 0.6 tablets/day for the 6M and 18M MPC groups).
(e) Reduced need for additional surgical and non-surgical
interventions for persistent pain: MPC-treated patients had a
significantly reduced need for additional interventions at the
treated disc level, including surgical intervention (spine fusion,
discectomy or artificial disc replacement) or injection (epidural
steroid injection, rhizotomy or transforaminal injections), than
saline controls. By 12 months, 25% saline controls had undergone an
additional intervention, compared with 10% HA controls, 6.9% of 6M
MPC and only 3.3% of 18M MPC treated patients. By Kaplan-Meier
analysis of time to a first additional treatment intervention,
treatment with either 6M or 18M MPC significantly reduced the need
for additional interventions compared with saline treatment (p
equals 0.024 and p equals 0.010, respectively). -- Improvement in
function
(a) Reduction in mean disability score: At 12 months, MPC
treatment resulted in greater improvement in function than was seen
in controls, as measured by the Oswestry Disability Index (ODI).
Mean reduction in the ODI functional disability score was 43% for
the 18M MPC group, 35% for the 6M MPC group, 30% for HA controls,
and 28% for saline controls (p equals 0.09 for 18M MPC group vs
saline).
(b) Increased proportion of patients achieving minimal residual
functional disability: Minimal residual functional disability at 12
months was considered if the ODI score was less than or equal to
20. A greater proportion of MPC treated patients achieved minimal
residual functional disability at 12 months than controls (18M
group 39%, 6M group 36%, pooled controls 18%, p equals 0.14 and p
equals 0.14, respectively).
-- Improvement in disc stability
In patients with early disc degeneration (Pfirrmann MRI
degenerative grades below 5), increased translational movement of
the disc is a potential indicator of instability associated with
early disc degeneration and annular fissures seen on MRI and
pathologic examination. At 12 months, MPC-treated patients
demonstrated a significant reduction in radiographically-determined
translational movement of the disc, suggesting a treatment effect
on disc degeneration, anatomy, and improved disc stability. The 18M
MPC group had a mean translational movement of only 1.3%, the 6M
MPC group 2%, the HA group 2.5%, and the saline group 3.5% (p
equals 0.021 between groups). When adjusting translation per degree
of rotation (TPDR), a similar treatment effect on reduced
translational movement was seen in both the 6M and 18M MPC
groups.
-- Safety:
Allogeneic MPC treatment was well tolerated with the most
frequently reported adverse event, back pain, occurring across all
treatment groups.
About Chronic Degenerative Intervertebral Disc Disease
More than 6 million patients in the United States alone are
currently dealing with chronic back pain that has persisted for at
least three months, with around 3.5 million people affected by
moderate or severe degenerative intervertebral disc disease. The
United States Centers for Disease Control and Prevention's National
Center for Health Statistics reported in 2010 that low back pain
was the leading cause of pain, affecting 28% of American adults,
and the second most common cause of disability in American adults.
The United States lifetime prevalence of low back pain is estimated
to be at least 60 to 84%. Total costs of low back pain are
estimated to be between $100 billion and $200 billion annually, two
thirds of which are due to decreased wages and productivity.
Treatment for chronic back pain of discogenic origin includes
conservative treatment, analgesia, anti-inflammatory agents,
epidural steroid injections, and ultimately surgical intervention.
Discogenic back pain is the end result of a complex process
initiated by degeneration and loss of proteoglycan and water
content of the nucleus pulpous, and increased stress on and fissure
formation of the annulus fibrosis.
About Mesoblast
Mesoblast Limited (ASX:MSB; USOTC:MBLTY) is a world leader in
the development of biologic products for the broad field of
regenerative medicine. The Company's proprietary technologies
include its highly purified, immunoselected Stro-1/Stro-3 positive
Mesenchymal Precursor Cells (MPCs), culture-expanded Mesenchymal
Stem Cells (MSCs), Dental Pulp Stem Cells (DPSCs), and expanded
Hematopoietic Stem Cells (HSCs). Mesoblast's protein technologies
are based on factors derived from its proprietary cellular
platforms, including Stromal Derived Factor-1 (SDF-1). Mesoblast's
allogeneic or 'off-the-shelf' regenerative medicine products are
being developed for the treatment of conditions with significant
unmet medical needs. Product development focus is in four major and
distinct areas - systemic diseases with an underlying inflammatory
and immunologic etiology; cardiac and vascular diseases; orthopedic
diseases of the spine; and improving outcomes of bone marrow
transplantation associated with oncology or genetic conditions.
www.mesoblast.com
CONTACT: Julie Meldrum
Corporate Communications
Mesoblast Limited
T: +61 (0) 3 9639 6036
E: julie.meldrum@mesoblast.com
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