Pluristem Announces Positive 12-Month Data From the Use of PLX-PAD for the Treatment of Critical Limb Ischemia
Pluristem Therapeutics Inc.
03.11.2011 08:14
---------------------------------------------------------------------------
The Company's Phase I Trials, Regulated by the FDA & the Paul Ehrlich
Institute, Met All Endpoints
HAIFA, Israel, 2011-11-03 08:14 CET (GLOBE NEWSWIRE) --
Pluristem Therapeutics, Inc. (Nasdaq:PSTI) (TASE:PLTR) today announced
positive 12-month data from its Phase I open-label, dose-escalation clinical
trials conducted under protocols approved by the Food & Drug Administration
(FDA) in the USA and the Paul-Ehrlich-Institute (PEI) in Germany. PLX-PAD cells
met all the clinical studies' protocol endpoints, demonstrating a safe
immunologic profile at all dosage levels and found to be potentially effective
in treating patients suffering from Critical Limb Ischemia (CLI).
Edwin Horwitz, MD, PhD, Associate Professor of Pediatrics at the Children's
Hospital of Philadelphia, President of the International Society for Cellular
Therapy (ISCT), and Chairman of Pluristem's Scientific Advisory Board, will
present the 12-month follow-up results at the World Conference on Regenerative
Medicine on November 3, 2011 in Leipzig, Germany.
The endpoints of these Phase I trials included data on tumorigenesis, adverse
events, immunological reactions, laboratory and ECG findings. The results of
these two trials are combined for reporting purposes.
No malignancies were reported and all serum sample levels of tumor markers
(PSA, CEA, CA125, AFF and NSE) were within normal range for all patients
tested. Monitoring for malignancies was required only in the clinical trial
conducted in Germany. It was concluded that treatment with PLX-PAD cells does
not induce tumorigenesis.
No clinical evidence of adverse events or toxicities related to the
intramuscular (IM) administration of PLX-PAD cells was observed in twenty-six
of twenty-seven patients. Only one patient in the US trial experienced a
transient local cutaneous inflammation after PLX-PAD was administered. A
transient change was noted in the leukocyte and lymphocyte count in the
patients, which returned to pre-injection baseline levels within 7 days and
without evidence of absolute lymphopenia. No ECG abnormalities were detected
during the treatment and monitoring periods.
Additionally, five of the twenty-seven patients received a double dose of
PLX-PAD cells from the same placental batch two weeks apart without evidence of
adverse events.
Based on the above data it was concluded there were no significant safety
issues and PLX-PAD cells can be safely given IM to patients without matching,
even if the patients are dosed twice from the same placental source.
Trends Towards Efficacy Based on Amputation Free Survival (AFS):
According to the study protocols, the clinical follow up was completed 3 months
after the administration of PLX-PAD cells. During that time, statistically
significant improvements were noted for the following efficacy parameters (see
press release announcement from September 14, 2011):
-- Ankle-Brachial Index (ABI) - a measure of blood flow (P=0.033).
-- Transcutaneous Oxygen Pressure (TcPO2) - a measure of tissue oxygenation
(P=0.05)
-- Quality of Life (QoL) - (P< 0.001)
-- Visual Analogue Score (VAS) - a measure of pain (P=0.013)
The European Medical Agencies (EMA) and the FDA require the primary endpoint
for CLI pivotal clinical trials to be Amputation Free Survival (AFS) rate. AFS
data was collected during the Phase I studies and compared with another
published CLI trial's data.
From a total of twenty-seven patients, four treatment failures occurred during
the observation period of twelve months, which resulted in an AFS rate of
85.2%, as opposed to historical control data of 66.8% for the same time period.
This corresponded to an event rate of 14.8%, as opposed to historical control
data showing a 33.2% event rate, as outlined in Table 1 below.
Therefore, based on the endpoint of AFS at 12 months, it was concluded there is
a trend towards efficacy of PLX-PAD cells in the treatment of CLI.
Table 1: Cumulative Event Rate Comparison
To see a graphic of this table please go to the following link:
http://media.globenewswire.com/cache/11974/file/11850.pdf
Dr. Horwitz stated: 'AFS is the single most important endpoint in CLI clinical
trials. Even though these Phase I trials were not controlled studies, the data
collected in these trials on AFS indicate significant potential for PLX-PAD
cells in treating CLI patients.'
'The safety data from these trials provide strong evidence that supports our
business approach of using allogeneic PLX cells for various indications.' said
Zami Aberman, Chairman and CEO of Pluristem. 'The clinical trials also
demonstrated that PLX cells possess superior properties enabling a second, same
placental batch, dose administration, which will be translated into a
logistical advantage when the cells are commercialized. Additionally, the
ability to administer our 'off-the-shelf' cells in two doses without the need
for tissue matching could potentially prolong the therapeutic effect of PLX
cells in the treatment of CLI, via a 'booster' dose.'
About the Study Protocols
Two Phase I clinical studies were conducted in the USA and Germany in
accordance with protocols approved by the FDA and the PEI, respectively.
Twenty-seven CLI patients were treated with PLX-PAD cells and followed for 12
months following the administration of the initial doses in the USA and for 24
months in Germany. During the clinical follow up period patients underwent
clinical examinations, blood flow measurements, scores for quality of life and
pain, ECGs and peripheral blood samples were drawn during their follow up
visits for chemistry and immunological analysis.
Twenty-two of the twenty seven patients in the US and Germany received a single
course of PLX-PAD cells with either 30 or 50 IM injections above and below the
knee of the afflicted limb in a treatment that took, on average, approximately
20 minutes to complete. The remaining five US patients received a double dose
of PLX-PAD cells in two courses administered two weeks apart. These five
patients received both courses of PLX-PAD cells from the same placental batch.
This was done in order to test for a delayed immunological response. Three
dosage levels of 200, 300 and 600 million1 PLX-PAD cells were evaluated. The
five patients treated with the double dose of PLX-PAD cells received each a
total dose of 600 million PLX-PAD cells.
About the Immunological Data
From an immunological perspective, the administration of PLX-PAD cells
stimulated mostly transient non-specific immunological reactions .These
reactions were without clinical significance or symptoms. Additionally, IM
injections of up to 300 million PLX-PAD cells did not cause any PLX
cell-specific response.
In addition, five patients received a double dose of PLX-PAD cells two weeks
apart. There was no evidence of immediate clinical toxicity or adverse events
and vital signs remained stable in all patients. Additionally, there were no
significant changes noted in routine blood counts during the follow up periods.
From an immunological perspective, no significant changes were noted in the
patients' lymphocytes including CD3, CD4, and CD8 lymphocyte counts or the
CD4/CD8 ratio and in their Natural Killer (NK) cell population. A transient
decrease in antigen presenting cells was demonstrated within 24 hours of
PLX-PAD administration that returned to pre-PLX-PAD injection levels within one
week. This phenomenon may be attributed to the immuno-modulating quality of
PLX-PAD cells.
About Pluristem Therapeutics Inc.
Pluristem Therapeutics Inc. (Nasdaq:PSTI) (TASE:PLTR) is a leading developer
of placenta-based cell therapies. The company's patented PLX (PLacental
eXpanded) cells drug delivery platform releases a cocktail of therapeutic
proteins in response to a variety of local and systemic inflammatory diseases.
PLX cells are grown using the company's proprietary 3D micro-environmental
technology and are an off-the-shelf product that requires no tissue matching or
immune-suppression treatment prior to administration. The PLX-PAD comprehensive
clinical development plan has been recognized by both the EMA and FDA,
targeting a sub-population of 20 million patients in the Peripheral Artery
Disease (PAD) market.
Data from two Phase I safety and dose determining clinical trials indicate that
Pluristem's first PLX product, PLX-PAD, is safe and potentially effective for
the treatment of end stage PAD. Pluristem's pre-clinical animal models have
demonstrated PLX cells are also potentially effective in nerve pain and muscle
damage when administered locally and in inflammatory bowel disease, MS and
stroke when administered systemically.
Pluristem has a strong patent portfolio, GMP certified manufacturing and
research facilities, strategic relationships with major research institutions
and a seasoned management team.
For more information visit www.pluristem.com and follow Pluristem on Twitter
@Pluristem, the content of which is not part of this press release.
CLICK HERE to watch a video where CLI patients and doctors involved in the
clinical trials share their stories.
The Pluristem Therapeutics Inc. logo is available at
http://www.globenewswire.com/newsroom/prs/?pkgid=6882
Safe Harbor Statement
This press release contains forward-looking statements within the meaning of
the 'safe harbor' provisions of the Private Securities Litigation Reform Act of
1995 and federal securities laws. For example, we are using forward looking
statements when we discuss the 12-Month data from our clinical trials and the
conclusions we derive from it, or when we speak about our potential development
of placenta-derived stem cell treatments for a variety of illnesses or when we
say that data from two Phase I clinical trials indicate that Pluristem's first
PLX product, PLX-PAD, is safe and potentially effective for the treatment of
end stage PAD or that Pluristem's pre-clinical animal models have demonstrated
PLX cells are also potentially effective in nerve pain and muscle damage when
administered locally and in inflammatory bowel disease, MS and stroke when
administered systemically. These forward-looking statements are based on the
current expectations of the management of Pluristem only, and are subject to a
number of factors and uncertainties that could cause actual results to differ
materially from those described in the forward-looking statements. The
following factors, among others, could cause actual results to differ
materially from those described in the forward-looking statements: changes in
technology and market requirements; we may encounter delays or obstacles in
launching our clinical trials; our technology may not be validated as we
progress further and our methods may not be accepted by the scientific
community; we may be unable to retain or attract key employees whose knowledge
is essential to the development of our products; unforeseen scientific
difficulties may develop with our process; our products may wind up being more
expensive than we anticipate; results in the laboratory may not translate to
equally good results in real surgical settings; our patents may not be
sufficient; our products may harm recipients; changes in legislation; inability
to timely develop and introduce new technologies, products and applications;
loss of market share and pressure on pricing resulting from competition, which
could cause the actual results or performance of Pluristem to differ materially
from those contemplated in such forward-looking statements. Except as otherwise
required by law, Pluristem undertakes no obligation to publicly release any
revisions to these forward-looking statements to reflect events or
circumstances after the date hereof or to reflect the occurrence of
unanticipated events. For a more detailed description of the risks and
uncertainties affecting Pluristem, reference is made to Pluristem's reports
filed from time to time with the Securities and Exchange Commission.
1 Dose variance equals +/- 10%
CONTACT: Pluristem Therapeutics Inc.
William Prather R.Ph., M.D.
Sr. VP Corporate Development
1-303-883-4954
William.PratherMD@pluristem.com
Daya Lettvin
Director Investor & Media Relations
+972-54-674-5580
daya@pluristem.com
Media Contact
Matthew KriegerRuder Finn - for Pluristem
+972-54-467-6950
matthew@ruderfinn.co.il
News Source: NASDAQ OMX
03.11.2011 Dissemination of a Corporate News, transmitted by DGAP -
a company of EquityStory AG.
The issuer is solely responsible for the content of this announcement.
DGAP's Distribution Services include Regulatory Announcements,
Financial/Corporate News and Press Releases.
Media archive at www.dgap-medientreff.de and www.dgap.de
---------------------------------------------------------------------------
Language: English
Company: Pluristem Therapeutics Inc.
United States
Phone:
Fax:
E-mail:
Internet:
ISIN: US72940R1023
WKN:
End of Announcement DGAP News-Service
---------------------------------------------------------------------------
Pluristem Therapeutics Inc.
03.11.2011 08:14
---------------------------------------------------------------------------
The Company's Phase I Trials, Regulated by the FDA & the Paul Ehrlich
Institute, Met All Endpoints
HAIFA, Israel, 2011-11-03 08:14 CET (GLOBE NEWSWIRE) --
Pluristem Therapeutics, Inc. (Nasdaq:PSTI) (TASE:PLTR) today announced
positive 12-month data from its Phase I open-label, dose-escalation clinical
trials conducted under protocols approved by the Food & Drug Administration
(FDA) in the USA and the Paul-Ehrlich-Institute (PEI) in Germany. PLX-PAD cells
met all the clinical studies' protocol endpoints, demonstrating a safe
immunologic profile at all dosage levels and found to be potentially effective
in treating patients suffering from Critical Limb Ischemia (CLI).
Edwin Horwitz, MD, PhD, Associate Professor of Pediatrics at the Children's
Hospital of Philadelphia, President of the International Society for Cellular
Therapy (ISCT), and Chairman of Pluristem's Scientific Advisory Board, will
present the 12-month follow-up results at the World Conference on Regenerative
Medicine on November 3, 2011 in Leipzig, Germany.
The endpoints of these Phase I trials included data on tumorigenesis, adverse
events, immunological reactions, laboratory and ECG findings. The results of
these two trials are combined for reporting purposes.
No malignancies were reported and all serum sample levels of tumor markers
(PSA, CEA, CA125, AFF and NSE) were within normal range for all patients
tested. Monitoring for malignancies was required only in the clinical trial
conducted in Germany. It was concluded that treatment with PLX-PAD cells does
not induce tumorigenesis.
No clinical evidence of adverse events or toxicities related to the
intramuscular (IM) administration of PLX-PAD cells was observed in twenty-six
of twenty-seven patients. Only one patient in the US trial experienced a
transient local cutaneous inflammation after PLX-PAD was administered. A
transient change was noted in the leukocyte and lymphocyte count in the
patients, which returned to pre-injection baseline levels within 7 days and
without evidence of absolute lymphopenia. No ECG abnormalities were detected
during the treatment and monitoring periods.
Additionally, five of the twenty-seven patients received a double dose of
PLX-PAD cells from the same placental batch two weeks apart without evidence of
adverse events.
Based on the above data it was concluded there were no significant safety
issues and PLX-PAD cells can be safely given IM to patients without matching,
even if the patients are dosed twice from the same placental source.
Trends Towards Efficacy Based on Amputation Free Survival (AFS):
According to the study protocols, the clinical follow up was completed 3 months
after the administration of PLX-PAD cells. During that time, statistically
significant improvements were noted for the following efficacy parameters (see
press release announcement from September 14, 2011):
-- Ankle-Brachial Index (ABI) - a measure of blood flow (P=0.033).
-- Transcutaneous Oxygen Pressure (TcPO2) - a measure of tissue oxygenation
(P=0.05)
-- Quality of Life (QoL) - (P< 0.001)
-- Visual Analogue Score (VAS) - a measure of pain (P=0.013)
The European Medical Agencies (EMA) and the FDA require the primary endpoint
for CLI pivotal clinical trials to be Amputation Free Survival (AFS) rate. AFS
data was collected during the Phase I studies and compared with another
published CLI trial's data.
From a total of twenty-seven patients, four treatment failures occurred during
the observation period of twelve months, which resulted in an AFS rate of
85.2%, as opposed to historical control data of 66.8% for the same time period.
This corresponded to an event rate of 14.8%, as opposed to historical control
data showing a 33.2% event rate, as outlined in Table 1 below.
Therefore, based on the endpoint of AFS at 12 months, it was concluded there is
a trend towards efficacy of PLX-PAD cells in the treatment of CLI.
Table 1: Cumulative Event Rate Comparison
To see a graphic of this table please go to the following link:
http://media.globenewswire.com/cache/11974/file/11850.pdf
Dr. Horwitz stated: 'AFS is the single most important endpoint in CLI clinical
trials. Even though these Phase I trials were not controlled studies, the data
collected in these trials on AFS indicate significant potential for PLX-PAD
cells in treating CLI patients.'
'The safety data from these trials provide strong evidence that supports our
business approach of using allogeneic PLX cells for various indications.' said
Zami Aberman, Chairman and CEO of Pluristem. 'The clinical trials also
demonstrated that PLX cells possess superior properties enabling a second, same
placental batch, dose administration, which will be translated into a
logistical advantage when the cells are commercialized. Additionally, the
ability to administer our 'off-the-shelf' cells in two doses without the need
for tissue matching could potentially prolong the therapeutic effect of PLX
cells in the treatment of CLI, via a 'booster' dose.'
About the Study Protocols
Two Phase I clinical studies were conducted in the USA and Germany in
accordance with protocols approved by the FDA and the PEI, respectively.
Twenty-seven CLI patients were treated with PLX-PAD cells and followed for 12
months following the administration of the initial doses in the USA and for 24
months in Germany. During the clinical follow up period patients underwent
clinical examinations, blood flow measurements, scores for quality of life and
pain, ECGs and peripheral blood samples were drawn during their follow up
visits for chemistry and immunological analysis.
Twenty-two of the twenty seven patients in the US and Germany received a single
course of PLX-PAD cells with either 30 or 50 IM injections above and below the
knee of the afflicted limb in a treatment that took, on average, approximately
20 minutes to complete. The remaining five US patients received a double dose
of PLX-PAD cells in two courses administered two weeks apart. These five
patients received both courses of PLX-PAD cells from the same placental batch.
This was done in order to test for a delayed immunological response. Three
dosage levels of 200, 300 and 600 million1 PLX-PAD cells were evaluated. The
five patients treated with the double dose of PLX-PAD cells received each a
total dose of 600 million PLX-PAD cells.
About the Immunological Data
From an immunological perspective, the administration of PLX-PAD cells
stimulated mostly transient non-specific immunological reactions .These
reactions were without clinical significance or symptoms. Additionally, IM
injections of up to 300 million PLX-PAD cells did not cause any PLX
cell-specific response.
In addition, five patients received a double dose of PLX-PAD cells two weeks
apart. There was no evidence of immediate clinical toxicity or adverse events
and vital signs remained stable in all patients. Additionally, there were no
significant changes noted in routine blood counts during the follow up periods.
From an immunological perspective, no significant changes were noted in the
patients' lymphocytes including CD3, CD4, and CD8 lymphocyte counts or the
CD4/CD8 ratio and in their Natural Killer (NK) cell population. A transient
decrease in antigen presenting cells was demonstrated within 24 hours of
PLX-PAD administration that returned to pre-PLX-PAD injection levels within one
week. This phenomenon may be attributed to the immuno-modulating quality of
PLX-PAD cells.
About Pluristem Therapeutics Inc.
Pluristem Therapeutics Inc. (Nasdaq:PSTI) (TASE:PLTR) is a leading developer
of placenta-based cell therapies. The company's patented PLX (PLacental
eXpanded) cells drug delivery platform releases a cocktail of therapeutic
proteins in response to a variety of local and systemic inflammatory diseases.
PLX cells are grown using the company's proprietary 3D micro-environmental
technology and are an off-the-shelf product that requires no tissue matching or
immune-suppression treatment prior to administration. The PLX-PAD comprehensive
clinical development plan has been recognized by both the EMA and FDA,
targeting a sub-population of 20 million patients in the Peripheral Artery
Disease (PAD) market.
Data from two Phase I safety and dose determining clinical trials indicate that
Pluristem's first PLX product, PLX-PAD, is safe and potentially effective for
the treatment of end stage PAD. Pluristem's pre-clinical animal models have
demonstrated PLX cells are also potentially effective in nerve pain and muscle
damage when administered locally and in inflammatory bowel disease, MS and
stroke when administered systemically.
Pluristem has a strong patent portfolio, GMP certified manufacturing and
research facilities, strategic relationships with major research institutions
and a seasoned management team.
For more information visit www.pluristem.com and follow Pluristem on Twitter
@Pluristem, the content of which is not part of this press release.
CLICK HERE to watch a video where CLI patients and doctors involved in the
clinical trials share their stories.
The Pluristem Therapeutics Inc. logo is available at
http://www.globenewswire.com/newsroom/prs/?pkgid=6882
Safe Harbor Statement
This press release contains forward-looking statements within the meaning of
the 'safe harbor' provisions of the Private Securities Litigation Reform Act of
1995 and federal securities laws. For example, we are using forward looking
statements when we discuss the 12-Month data from our clinical trials and the
conclusions we derive from it, or when we speak about our potential development
of placenta-derived stem cell treatments for a variety of illnesses or when we
say that data from two Phase I clinical trials indicate that Pluristem's first
PLX product, PLX-PAD, is safe and potentially effective for the treatment of
end stage PAD or that Pluristem's pre-clinical animal models have demonstrated
PLX cells are also potentially effective in nerve pain and muscle damage when
administered locally and in inflammatory bowel disease, MS and stroke when
administered systemically. These forward-looking statements are based on the
current expectations of the management of Pluristem only, and are subject to a
number of factors and uncertainties that could cause actual results to differ
materially from those described in the forward-looking statements. The
following factors, among others, could cause actual results to differ
materially from those described in the forward-looking statements: changes in
technology and market requirements; we may encounter delays or obstacles in
launching our clinical trials; our technology may not be validated as we
progress further and our methods may not be accepted by the scientific
community; we may be unable to retain or attract key employees whose knowledge
is essential to the development of our products; unforeseen scientific
difficulties may develop with our process; our products may wind up being more
expensive than we anticipate; results in the laboratory may not translate to
equally good results in real surgical settings; our patents may not be
sufficient; our products may harm recipients; changes in legislation; inability
to timely develop and introduce new technologies, products and applications;
loss of market share and pressure on pricing resulting from competition, which
could cause the actual results or performance of Pluristem to differ materially
from those contemplated in such forward-looking statements. Except as otherwise
required by law, Pluristem undertakes no obligation to publicly release any
revisions to these forward-looking statements to reflect events or
circumstances after the date hereof or to reflect the occurrence of
unanticipated events. For a more detailed description of the risks and
uncertainties affecting Pluristem, reference is made to Pluristem's reports
filed from time to time with the Securities and Exchange Commission.
1 Dose variance equals +/- 10%
CONTACT: Pluristem Therapeutics Inc.
William Prather R.Ph., M.D.
Sr. VP Corporate Development
1-303-883-4954
William.PratherMD@pluristem.com
Daya Lettvin
Director Investor & Media Relations
+972-54-674-5580
daya@pluristem.com
Media Contact
Matthew KriegerRuder Finn - for Pluristem
+972-54-467-6950
matthew@ruderfinn.co.il
News Source: NASDAQ OMX
03.11.2011 Dissemination of a Corporate News, transmitted by DGAP -
a company of EquityStory AG.
The issuer is solely responsible for the content of this announcement.
DGAP's Distribution Services include Regulatory Announcements,
Financial/Corporate News and Press Releases.
Media archive at www.dgap-medientreff.de and www.dgap.de
---------------------------------------------------------------------------
Language: English
Company: Pluristem Therapeutics Inc.
United States
Phone:
Fax:
E-mail:
Internet:
ISIN: US72940R1023
WKN:
End of Announcement DGAP News-Service
---------------------------------------------------------------------------