For
FDA Approves Orphan Drug Status for Revolutionary
LOS ANGELES, Calif.
Orphan Drug status allows for
This ground-breaking new drug
· · · ·
The
The
Contact: Barry Sugarman, B.S.ENGR., President, The |
http://www.aacr.org/home/public–media/news.aspx?d=1112
http://clincancerres.aacrjournals.org/cgi/content/abstract/14/15/4850
Requests for reprints: Crystal L. Mackall,
Pediatric Oncology Branch, Center for Cancer Research, National Cancer
Institute, NIH, 10-CRC/1W-3940, 10 Center Drive, MSC 1104, Bethesda, MD
20892-1104. Phone: 301-402-5940; Fax: 301-451-7052; E-mail Crystal L. Mackall: cm35c@nih.gov
August 1, 2008
PHILADELPHIA – Based on a pilot study in children with sarcoma,
researchers at the National Institutes of Health (NIH) believe that
immunotherapy could prove beneficial in treating high-risk forms of
this cancer.
The researchers tested a novel dendritic vaccine as well as a
standard flu vaccine to potentially strengthen the immune system post
chemotherapy. Their findings, published in the August 1 issue of Clinical Cancer Research,
a journal of the American Association for Cancer Research, show that
although the dendritic vaccine they tested did not perform as well as
hoped, children participating in the study responded well to the
standard flu vaccine- suggesting that a strategy to bolster immune
function in these patients holds promise for fighting their cancer.
Researchers also found that survival in these patients was at the
higher end of what is generally seen with recurrent and/or metastatic
Ewing's sarcoma (ESFT) or alveolar rhabdomyosarcoma (AR) – the two
sarcomas tested in this single arm study. The 22 enrolled patients who
did not receive immunotherapy had a 31 percent five-year overall
survival, compared to 43 percent five-year survival in 30 patients who
ultimately received the novel immunotherapy.
Although the study is small, these early findings are promising,
says the study's senior investigator, Crystal Mackall, M.D., of the
National Cancer Institute's (NCI) Pediatric Oncology Branch. “We need
new therapies. While outcomes overall for these tumors have improved
during the past 40 years, there has not been substantial improvement
for patients with metastatic or recurrent disease. This study shows
that immunotherapy is safe and well tolerated, and could ultimately be
beneficial for this high risk population. Mackall calls the study a
rational approach to improving treatment of ESFT and AR. “We now know
that the immune system of patients recovering from chemotherapy is
malleable, so we just need to find the best immunologic approach to
exploit this window of opportunity,” she said.
Both ESFT and AR develop due to chromosomal translocations, which
fuse a gene from one chromosome to a different chromosome. The
dendritic vaccine included peptides derived from each patient's
individual cancer in a way that was designed to alert a patient's
immune system to the unique genetic alteration on the cancer cells.
In this clinical trial of 52 patients, researchers attempted to use
immunotherapy as “consolidation” therapy – that is, after standard
therapy provided a remission. Patients underwent aphaeresis to harvest
blood lymphocytes that were then frozen. From this, dendritic cells
were later extracted. These are cells that present an antigen to T
cells and other immune system fighters in order to elicit a response.
All patients then had chemotherapy, radiation or surgery, as
appropriate, and in some cases a stem cell transplant to induce
remission. The 30 patients who initiated immunotherapy received a
common flu vaccine, as well as their own lymphocytes and their own
dendritic cells, which had been infused with tumor antigens. Some of
these patients also received interleukin-2, which stimulates activity
of T cell lymphocytes.
“The good news was the surprisingly nice T cell response patients
had to the flu vaccination, even relatively soon after completing
chemotherapy,” Mackall said. “That shows that the general idea of using
immunotherapy following chemotherapy to prevent recurrence is not a
flawed one. Chemotherapy depleted the immune system, but we could
restore it.”
The bad news, she added, is that the dendritic vaccine “was not very
immunogenic. We have a long way to go to optimizing this vaccine.”
Current studies are underway to test a new version of the vaccine,
which utilizes more mature dendritic cells and tumor lysate in lieu of
the translocation peptides. Ultimately, effective immunotherapy
requires that one is capable of reproducing a strong and sustained
immune response to tumor antigens,” she said.
Mackall also notes that the vaccine in this trial was tested in
patients whose cancer had recurred or metastasized. If the favorable
safety profile continues and the efficacy of the vaccine is improved
with the subsequent versions, one could ultimately consider the use of
immunotherapy to consolidate remission in lower risk populations.
# # #
The mission of the American Association for Cancer Research is to
prevent and cure cancer. Founded in 1907, AACR is the world's oldest
and largest professional organization dedicated to advancing cancer
research. The membership includes more than 28,000 basic, translational
and clinical researchers; health care professionals; and cancer
survivors and advocates in the United States and 80 other countries.
AACR marshals the full spectrum of expertise from the cancer community
to accelerate progress in the prevention, diagnosis and treatment of
cancer through high-quality scientific and educational programs. It
funds innovative, meritorious research grants. The AACR Annual Meeting
attracts more than 17,000 participants who share the latest discoveries
and developments in the field. Special conferences throughout the year
present novel data across a wide variety of topics in cancer research,
treatment and patient care. AACR publishes five major peer-reviewed
journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication and its sixth major journal, Cancer Prevention Research, is dedicated exclusively to cancer prevention, from preclinical research to clinical trials. The AACR also publishes CR, a magazine for cancer survivors and their families, patient advocates, physicians and scientists. CR
provides a forum for sharing essential, evidence-based information and
perspectives on progress in cancer research, survivorship and advocacy.
Media Contact:
Jeremy Moore
267-646-0557
Jeremy.moore@aacr.org
SAN MARINO, Calif., May 29, 2008 — Epeius Biotechnologies
(http://www.epeiusbiotech.com)
announced today the results of an on-going Phase I/II study of Rexin-G
for metastatic bone and soft tissue sarcoma (J Clin Oncol 26: 14509,
2008). Rexin-G is the first and so far only targeted gene therapy
vector that has been tested in the clinic (Nature Reviews/Genetics
2007). In this open label study, cohorts of 6 to 7 patients with all
types of sarcoma, including osteosarcoma, Ewing's sarcoma,
leiomyosarcoma, malignant fibrous histiocytoma, chondrosarcoma,
fibrosarcoma, liposarcoma, angiosarcoma, spindle cell sarcoma, and
malignant mixed Mullerian tumor of ovary, were treated with 1 x 10e11
cfu Rexin-G, administered i.v. over 5 minutes, 2 times a week for 4
weeks (Cumulative Dose = 8 x 10e11 cfu) followed by a 2-week rest
period. Patients with Grade 1 or less toxicity were given progressive
intra-patient dose-escalations consisting of additional treatment
cycles of 1 to 2 x 10e11 cfu three times a week for 4 weeks (Cumulative
Dose per cycle: 1.2-2.4 x 10e12 cfu).
These higher dosing regimens were associated with prolonged disease
stabilization and a median overall survival of greater than 6 months,
which was three times longer than that observed in the low-dose group.
Further, histologic examination of resected tumors showed 50-90%
necrosis. No dose-limiting toxicity was observed, even at the higher
doses of Rexin-G, thus confirming that repeated infusions of Rexin-G
are safe and well-tolerated. Taken together with previous clinical
studies conducted in the Philippines and Japan, these studies confirm
the exemplary safety and dose-dependent efficacy of Rexin-G in a broad
spectrum of chemotherapy-resistant cancers.
For more information about Rexin-G, on-going clinical trials in
the USA and abroad, and/or Epeius pathotropic (disease-seeking) gene
delivery systems, please contact Dr. Erlinda M. Gordon at . egordon@epeiusbiotech.com
CONTACT: Erlinda M. Gordon, M.D., of Epeius Biotechnologies Corporation,+1-626-441-6695, egordon@epeiusbiotech.com
Web site: http://www.epeiusbiotech.com/
ADVIGO CP-751,871 Global Phase III Clinical Trial Program
Initiated (ADVancing IGF-1R in Oncology)
CHICAGO–Pfizer announced today results from several clinical trials further
describing the activity of its investigational compound CP-751,871 in
non-small cell lung cancer (NSCLC) and Ewing’s
Sarcoma, both diseases with high unmet medical need. The three oral
presentations and one poster discussion underscore that the insulin-like
growth factor receptor (IGF-1R) is increasingly recognized by the
medical community as a relevant target for investigation in cancer
research. The results were presented at the 44th
Annual Meeting of the American Society of Clinical Oncology (ASCO) in
Chicago, IL.
Updated Response Data from the 1002 NSCLC Trial
Updated study results from a Phase II, randomized, non-comparative study
showed 54 percent of patients with Stage III/IV treatment-naïve
NSCLC receiving the combination CP-751,871 plus carboplatin and
paclitaxel (n=97) experienced objective responses. The response rate
observed for patients treated with carboplatin and paclitaxel alone was
41 percent.
Of note, 78 percent of a subset of patients with squamous cell carcinoma
(n=23) and 57 percent of a subset of patients with adenocarcinoma (n=28)
receiving 20 mg/kg of CP-751,871 plus carboplatin and paclitaxel
experienced objective responses. Response rates were 46 percent and 25
percent, respectively, for squamous cell (n=13) and adenocarcinoma
patients (n=20) receiving carboplatin and paclitaxel alone. No response
advantage with CP-751,871 was seen in a subset of patients with
undifferentiated tumors (Not otherwise specified, NOS).
“Patients with advanced NSCLC typically face a
poor prognosis and we need to develop new strategies and new treatment
combinations to improve their survival,” said
lead investigator Daniel Karp, M.D., director of the M.D. Anderson
Cancer Center Clinical and Translational Research Center (CTRC). “The
updated study results add to our growing understanding of the potential
safety and efficacy of CP-751,871. In this trial, increasing the dose to
20 mg/kg in Stage 2 of the trial resulted in an increased overall
response rate in all differentiated histologies, including
adenocarcinoma, non-adenocarcinoma, and particularly in squamous
histologies, which we consider to be of interest for future study.”
Dr. Karp also presented progression-free survival (PFS) results from the
study. At the dose level of 20 mg/kg, the observed progression-free
survival was 5 months in the CP-751,871 plus carboplatin/paclitaxel arm
and 4 months in the carboplatin/paclitaxel only arm. The highest
observed PFS was in the group of patients with squamous histologies (5.6
months in the CP-751,871 plus carboplatin/paclitaxel arm and 4.3 months
in the carboplatin/paclitaxel only arm) corresponding to the patients
that demonstrated the highest response rates. PFS was defined as either
the length of time before the cancer progressed or death.
In this study, CP-751,871 was generally well tolerated. The most common
Grade 3 or 4 side effects reported were hyperglycemia (increased blood
sugar) (20 percent) and neutropenia (30 percent).
Correlative Science Study Results Support Karp Data
This abstract summarized ancillary studies conducted to investigate the
molecular make up of lung tumors and its relevance to anti-IGF-IR
therapy. Members of the IGF-IR pathway appear to be expressed
differentially across lung tumor histologies which may help to explain
the differential activity of CP-751,871 across these histologies. Tumor
differentiation also appears to play a role. Data were also presented
demonstrating that EGFR inhibition sensitizes tumors to CP-751,871
treatment.
“These results help us to understand better
how CP-751,871 works, provide support for our phase III trial strategy
and underscore Pfizer’s commitment to bring
science and innovation to the forefront of drug development,”
said Antonio Gualberto, M.D., Ph.D., Global Clinical Lead for the
CP-751,871 program, Pfizer Global Research and Development.
ADVIGO Phase III Registration
Program (ADVancing IGF-IR in Oncology)
Based on these data, Pfizer has initiated a large global Phase III
clinical trial program for CP-751,871 in NSCLC, including some studies
with patients with non-adenocarcinoma (ADVIGO 1016, ADVIGO 1018). The
program includes trials for patients who are newly diagnosed and for
those who have already been treated with other therapies.
Pfizer has made a major commitment to CP-751,871 and has invested
significant resources in the Phase III program, which will include more
than 2,000 patients around the world.
For more information on the ADVIGO registration program please visit, http://PfizerCancerTrials.com.
Preliminary Data Presented on CP-751,871 in Sarcoma
Phase I data presented at ASCO showed single agent CP-751,871 was
generally well-tolerated in patients with relapsed or refractory sarcoma
(n=22), including Ewing’s sarcoma (n=9). A
response of stable disease or better was seen in 12 out of 20 evaluable
patients, including one confirmed partial response in a 12-year-old
patient with Ewing’s sarcoma, the second most
common malignant bone tumor in young patients and the most deadly bone
tumor.
CP-751,871 was generally well tolerated in patients with relapsed or
refractory sarcoma. Grade 3 or 4 treatment-related side effects reported
included Grade 4 uric acid increase (n=1) and Grade 3 bilateral
deep-vein thrombosis (n=1).
About CP-751,871
CP-751,871, a fully human IgG2 monoclonal antibody, is a highly specific
inhibitor of the IGF-1R pathway. It is believed that through this
inhibition, CP-751,871 blocks one of the key signaling pathways in
cancer cells that lead to uncontrolled growth and survival of tumor
cells.
Pfizer recently initiated a global Phase III clinical trial registration
program for CP-751,871 in non-adenocarcinoma NSCLC. In addition, Pfizer
is studying CP-751,871 in clinical trials for the treatment of many
other cancers, including prostate, breast and colon cancers and Ewing’s
sarcoma. To date, more than 500 patients have participated in CP-751,871
clinical trials in multiple tumor types.
About Pfizer Oncology
Pfizer Oncology is committed to the discovery, investigation and
development of treatments and currently has 22 innovative compounds in
clinical development across four platforms. By leveraging the strength
of our resources and scientific talent, Pfizer Oncology strives to
discover and develop novel treatment options to improve the outlook for
oncology patients. Pfizer currently devotes more than 22 percent of its
total R&D budget to the field of oncology, investing annually in
worldwide research initiatives. We also partner with healthcare
providers, governments and local communities around the world to provide
better quality healthcare and health system support.
For more information on the above information, please visit http://www.Pfizer.com.
DISCLOSURE NOTICE: The information contained in this release is as of
June 2, 2008. Pfizer assumes no obligation to update any forward-looking
statements contained in this release as the result of new information or
future events or developments.
This release contains forward-looking information about a product
candidate, CP-751,871, including its potential benefits, that involves
substantial risks and uncertainties. Such risks and uncertainties
include, among other things, the uncertainties inherent in research and
development; decisions by regulatory authorities regarding whether and
when to approve any drug applications that may be filed for such product
candidate as well as their decisions regarding labeling and other
matters that could affect its availability or commercial potential; and
competitive developments.
A further description of risks and uncertainties can be found in
Pfizer’s Annual Report on Form 10-K for the
fiscal year ended December 31, 2007 and in its reports on Form 10-Q and
Form 8-K.
Pfizer Inc
Media:
Vanessa Aristide, 917-697-0481 or
212-733-3784
or
Investors:
Jennifer Davis, 212-733-0717
Investigators from the Children’s Oncology Group (COG) have found for the first time that giving combination chemotherapy every two weeks is more effective than the same therapy given every three weeks in patients with Ewing’s sarcoma, without increasing side effects.
“These findings are convincing enough to change the standard of care for patients with localized Ewing’s sarcoma,” said lead author Richard B. Womer, MD, senior oncologist and professor of pediatrics at the Children’s Hospital of Philadelphia and the University of Pennsylvania School of Medicine. “This study shows that progress against Ewing’s sarcoma can be made by giving commonly used anti-cancer drugs in new ways.”
Ewing’s sarcoma is a cancer that most often develops in the bones but can also form in soft tissue. It is generally diagnosed in children. Until this study, the standard treatment for this cancer included chemotherapy with the drugs vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide given every three weeks, as well as surgery and/or radiation therapy. With the development of better ways to bolster the immune and blood-forming systems of the body—enabling patients to tolerate more frequent chemotherapy—researchers seeking to improve treatments for several types of cancer have hypothesized that giving chemotherapy more frequently might be more effective than conventional approaches, without causing undue side effects.
In this study, researchers at 160 COG institutions sought to determine if giving the same five drugs every two weeks was more effective than giving them every three weeks in patients with Ewing’s sarcoma who were younger than 50 and had not yet had chemotherapy or radiation therapy. Primary treatment (surgery, radiation therapy, or both) began 13 weeks after chemotherapy was initiated. Event-free survival (the percentage of patients who did not die or experience a relapse or second cancer) was compared between 284 patients who received chemotherapy every two weeks and 284 who received the same regimen every three weeks. Patients in both groups received a total of 14 cycles of chemotherapy.
After a median follow-up of three years, event-free survival was 76 percent among the patients who received chemotherapy every other week, compared with 65 percent among those who received chemotherapy every three weeks. The incidence and severity of side effects remained similar between the two groups. Fever with low white blood cell count occurred in 7 percent
of those in the two-week arm and 6 percent of those in the three-week
arm; the incidence of infection was 4.8 percent and 4.6 percent,
respectively.
Abstract #10504
Randomized comparison of every-two-week v. every-three-week
chemotherapy in Ewing sarcoma family tumors (ESFT). R. B. Womer, D. C.
West, M. D. Krailo, P. S. Dickman, B. Pawel, E. for the Children's
Oncology Group AEWS0031 Committee
Background: Chemotherapy with
alternating cycles of vincristine-doxorubicin-cyclophosphamide and
ifosfamide-etoposide, and primary tumor treatment with surgery and/or
radiation therapy, is the usual approach to localized ESFT in North
America. We conducted a trial asking whether chemotherapy
intensification through interval compression could improve outcome.
Methods: This was a prospective
randomized-controlled trial for patients less than 50 y old with
extra-dural ESFT, without distant metastases or prior chemotherapy or
radiation therapy; and with adequate renal, cardiac, and hepatic
function. Patients were treated with vincristine (2 mg/sq.m, max. 2
mg), doxorubicin (75 mg/sq.m) and cyclophosphamide (1.2 g/sq.m)
alternating with ifosfamide (9 g/sq.m) and etoposide (100 mg/sq.m/),
for 14 cycles, with filgrastim (5 mg/kg/day, maximum 300 mg) between
cycles. Patients assigned to Regimen A were scheduled to begin
chemotherapy cycles every 21 days, and patients assigned to Regimen B
were scheduled to begin cycles every 14 days, or when ANC > 750 and
platelets > 75. Primary tumor treatment (surgery, radiation, or
both) was scheduled to begin week 13 (after 4 cycles in Regimen A and 6
cycles in Regimen B). The primary endpoint was event-free survival
using a two-sided log-rank test with size 0.05 and power 0.8 to detect
a 13% Embargoed Until May 15, 2008 at 9:00pm (EDT) 12 change in EFS
from 60%, with 264 patients in each arm.
Results: 587 patients were
enrolled and randomized, and 568 were eligible, 284 in each regimen.
For all courses, the median cycle interval for Regimen A was 21 days,
mean 23.3 days; in Regimen B, the median interval was 15 days, mean
18.5 days. Event-free survival at a median of 3 years was 65% in
Regimen A and 76% in Regimen B, p=0.028. The occurrence of specific
toxicities and the number of hospital days were similar for the two
regimens.
Conclusions: Every-2-week chemotherapy is more effective than every-three-week chemotherapy for localized ESFT, with no increase in toxicity.
Disclosures for Research Team: Nothing to disclose.
http://ir.ziopharm.com/releasedetail.cfm?ReleaseID=300540
BETHESDA,
Md., Mar 20, 2008 (BUSINESS WIRE) — ZIOPHARM Oncology, Inc.
(NASDAQ:ZIOP) announced today that it presented promising early data
from a Phase Ib study of indibulin, the Company's novel, orally
administered, synthetic tubulin targeted agent, at the 6th
International Symposium on Targeted Anticancer Therapies held in
Bethesda, Maryland, March 20 to 22.
A
total of 14 patients with a variety of cancers, including sarcomas and
carcinomas, have been treated to date in the study. Following a total
of 30 cycles of treatment, indibulin has been shown to be very well
tolerated, with no drug-related Grade 2 or higher toxicities reported.
Of note, no neurotoxicities, a common and serious side effect typically
associated with microtubule targeting agents, have been observed.
In
addition to confirming indibulin's safety profile, this study evaluates
early treatment responses by PET scans. Among 8 evaluable patients,
these PET scans demonstrated a substantial anti-tumor effect by
indibulin. Week 7 PET scans identified 1 complete reduction in uptake,
4 with partial reduction in uptake, and 3 with increased uptake. Tumor
responses measured by PET scan are generally referred to as metabolic
responses, and usually correlate with treatment responses in cancer.
“Safely
and effectively targeting microtubules in cancer cells has long been a
goal of researchers as it leads to a variety of anti-cancer activity,
including antiangiogenesis and antimetastasis,” commented Sant P.
Chawla, MD, Director, Sarcoma Oncology Center and a lead investigator
of the study. “Yet to date, these agents have all demonstrated serious
side effects. Oral indibulin, by contrast, has been very well
tolerated, with none of the neurotoxicity or bone marrow suppression
seen with taxanes and vinca alkaloids. Indibulin has also demonstrated
promising early activity by PET scan, including a complete response in
Ewing's Sarcoma and a partial response in a neuroendocrine cancer.
Taken together, these results are highly compelling, making ongoing
study a priority.”
For more details on these trials please see www.clinicaltrials.gov.
About Indibulin
Indibulin
is a novel synthetic anti-mitotic agent that binds to tubulin,
destabilizes microtubule polymerization, arrests tumor cell growth at
the G2/M phase and inhibits cell mobility and metastasis. Microtubules
are well-established targets for anti-cancer drug development and
tubulin-binding drugs such as taxanes and vinca alkaloids are currently
widely used to treat cancer. Indibulin is orally available, lacks
neurotoxicity and has efficacy in taxane refractory preclinical models.
About ZIOPHARM Oncology, Inc.
ZIOPHARM Oncology, Inc. is a
biopharmaceutical company engaged in the development and
commercialization of a diverse, risk-sensitive portfolio of in-licensed
cancer drugs to address unmet medical needs. The Company applies new
insights from molecular and cancer biology to understand the efficacy
and safety limitations of approved and developmental cancer therapies
and identifies proprietary and related molecules for better patient
treatment. For more information, visit www.ziopharm.com.
Forward-Looking Safe Harbor Statement:
This
press release contains forward-looking statements for ZIOPHARM
Oncology, Inc. that involve risks and uncertainties that could cause
the Company's actual results to differ materially from the anticipated
results and expectations expressed in these forward-looking statements.
These statements are based on current expectations, forecasts and
assumptions that are subject to risks and uncertainties, which could
cause actual outcomes and results to differ materially from these
statements. Among other things, there can be no assurance that any of
the Company's development efforts relating to its product candidates
will be successful, or such product candidates will be successfully
commercialized. Other risks that affect forward-looking information
contained in this press release include the possibility of being unable
to obtain regulatory approval of the Company's product candidates, the
risk that the results of clinical trials may not support the Company's
claims, and risks related to the Company's ability to protect its
intellectual property and its reliance on third parties to develop its
product candidates. The Company assumes no obligation to update these
forward-looking statements, except as required by law.
ZIOP-G
SOURCE: ZIOPHARM
Oncology, Inc.
ZIOPHARM Oncology, Inc.
Suzanne McKenna, 646-214-0703
smckenna@ziopharm.com
or
Argot Partners
Andrea Rabney, 212-600-1902
andrea@argotpartners.com
Apr. 15, 2008
See AMG 479 Release For Ewing's Sarcoma Below
Early Data Presented from Investigational Molecules that Target
Apoptosis and Growth Regulation Pathways
Abstract Numbers: 3162, 1326, 3999, 2804, 4001, 3994
SAN DIEGO–(BUSINESS WIRE)–April 15, 2008–Amgen (NASDAQ:AMGN)
today announced data generated by the company's robust oncology
research and development programs in the areas of apoptosis
(programmed cell death) and cell growth regulation. The data,
presented at the American Association for Cancer Research (AACR)
Annual Meeting in San Diego were from five preclinical studies
evaluating anti-tumor activity, pharmacodynamics, and potential
pre-clinical and clinical biomarkers for investigational molecules AMG
655, AMG 479 and AMG 102.
“We are excited to be pushing the boundaries of knowledge around
known oncology pathways such as apoptosis and growth regulation by
exploring new and innovative approaches to attack tumor cells,” said
David Chang, M.D., vice president, Global Oncology Development at
Amgen. “While still early, we are pleased to be presenting a broad
spectrum of data at this meeting reinforcing the biologic plausibility
of targeting newly-discovered approaches to attack cancer via these
pathways.”
Targeting Apoptosis via Death Receptors
AMG 655 is an investigational fully human monoclonal antibody
(mAb) agonist directed against death receptor 5 (DR5). AMG 655 is
designed to activate caspases and induce apoptosis in sensitive tumor
cells.
Apoptosis is a form of cell suicide in which a controlled sequence
of biochemical events leads to cell death. In cancer, the
dysregulation of apoptosis is critical in the development and survival
of tumors. Apoptosis can be triggered by cell stress and DNA damage,
but it also occurs normally during development of the body.
Data presented at AACR showed that, when combined with the
chemotherapeutic agent gemcitabine, AMG 655 enhanced apoptosis in both
in vitro, and in vivo, pancreatic cancer models. The combination of
AMG 655 and gemcitabine was more effective in these models than either
agent alone.
In another study, AMG 655 was combined with a chemotherapeutic
agent (irinotecan or 5-fluorouracil (5-FU)) enhanced apoptosis
relative to either agent alone in both in vitro and in vivo colon
cancer cell models. AMG 655 is currently being tested against
colorectal cancer in a Phase 1b/2 clinical trial.
In a third study, positron emission tomography (PET) was evaluated
for its potential as a non-invasive method to measure receptor
occupancy of DR5, the target of AMG 655. The preclinical results
support the potential of using PET for imaging DR5 positive tumors and
measuring receptor occupancy in patients. This imaging technology also
is being applied to the study of other antibodies in the Amgen
pipeline.
Targeting Growth Regulation in Cancer
AMG 479 is an investigational fully human monoclonal antibody that
binds to insulin-like growth factor-1 receptor (IGF-1R) without
cross-reacting with the closely related insulin receptor.
IGF-1 and IGF-2 activate the IGF-1R receptor, which is expressed
in many human cancers. The expression of IGF-1 mediates tumor
proliferation and reduces apoptosis and is associated with higher
incidences and more aggressive progression of many common cancers.
Activation of these growth and survival pathways may allow tumor
cells to resist the apoptosis-inducing activity of chemotherapy,
radiation, and hormonal therapy and can increase cellular
proliferation.
The preclinical data presented showed that AMG 479 inhibited more
than 80 percent of IGF-1 induced growth activation in certain sarcoma
cell line. Treatment of these cell lines with a combination of AMG 479
and cyclophosphamide resulted in significant (p=0.0020 vs. AMG 479,
p=0.0002 vs. cyclophosphamide) tumor growth inhibition compared to
either treatment alone. AMG 479 is currently in phase 2 Ewing's
sarcoma trial.
AMG 102
AMG 102 is an investigational fully human monoclonal antibody that
targets the action of anti-hepatocyte growth factor (HGF)/scatter
factor (SF). HGF signaling through its receptor c-Met appears to play
an important role in many types of human cancers.
The HGF/SF:c-Met pathway mediates a large number of normal
activities in cells of epithelial origin – including proliferation,
survival, migration, and invasion. The dysregulation of the
HGF/SF:c-Met pathway appears to play an important role in many types
of cancers, often leading to tumorigenesis and metastasis.
The data presented at AACR examined exploratory biomarkers that
might be useful pharmacodynamic or patient enrichment markers for
HGF/SF:c-Met therapies like AMG 102. Preclinical glioblastoma tumor
xenograft models were treated with a single dose of AMG 102 ranging
from 3- 300 ug IP. On days 3 and 7 after treatment initiation, plasma
was harvested and levels of tumor-derived total human HGF, soluble
human c-Met and CD44v6 (a c-Met associated protein) were quantified.
Plasma samples from patients enrolled in the AMG 102 first-in-human
trial were also examined. Total HGF and soluble c-Met levels were
determined in plasma from patients in sequential dose cohorts (4-6
pts/cohort) that had been treated with AMG 102 at 0.5, 1, 3, 5, 10, or
20 mg/kg.
The study found that the treatment of tumor bearing preclinical
models or cancer patients with AMG 102 gave rise to a dose-dependent
increase in circulating HGF levels which suggests that monitoring HGF
levels during treatment may serve as a biomarker for inhibition of the
HGF/SF:c-Met pathway
.
About Amgen
Amgen discovers, develops, manufactures and delivers innovative
human therapeutics. A biotechnology pioneer since 1980, Amgen was one
of the first companies to realize the new science's promise by
bringing safe and effective medicines from lab, to manufacturing
plant, to patient. Amgen therapeutics have changed the practice of
medicine, helping millions of people around the world in the fight
against cancer, kidney disease, rheumatoid arthritis and other serious
illnesses. With a deep and broad pipeline of potential new medicines,
Amgen remains committed to advancing science to dramatically improve
people's lives. To learn more about our pioneering science and our
vital medicines, visit www.amgen.com.
Forward-Looking Statements
This news release contains forward-looking statements that are
based on management's current expectations and beliefs and are subject
to a number of risks, uncertainties and assumptions that could cause
actual results to differ materially from those described. All
statements, other than statements of historical fact, are statements
that could be deemed forward-looking statements, including estimates
of revenues, operating margins, capital expenditures, cash, other
financial metrics, expected legal, arbitration, political, regulatory
or clinical results or practices, customer and prescriber patterns or
practices, reimbursement activities and outcomes and other such
estimates and results. Forward-looking statements involve significant
risks and uncertainties, including those discussed below and more
fully described in the Securities and Exchange Commission (SEC)
reports filed by Amgen, including Amgen's most recent annual report on
Form 10-K and most recent periodic reports on Form 10-Q and Form 8-K.
Please refer to Amgen's most recent Forms 10-K, 10-Q and 8-K for
additional information on the uncertainties and risk factors related
to our business. Unless otherwise noted, Amgen is providing this
information as of April 14, 2008 and expressly disclaims any duty to
update information contained in this news release.
No forward-looking statement can be guaranteed and actual results
may differ materially from those we project. Discovery or
identification of new product candidates or development of new
indications for existing products cannot be guaranteed and movement
from concept to product is uncertain; consequently, there can be no
guarantee that any particular product candidate or development of a
new indication for an existing product will be successful and become a
commercial product. Further, preclinical results do not guarantee safe
and effective performance of product candidates in humans. The
complexity of the human body cannot be perfectly, or sometimes, even
adequately modeled by computer or cell culture systems or animal
models. The length of time that it takes for us to complete clinical
trials and obtain regulatory approval for product marketing has in the
past varied and we expect similar variability in the future. We
develop product candidates internally and through licensing
collaborations, partnerships and joint ventures. Product candidates
that are derived from relationships may be subject to disputes between
the parties or may prove to be not as effective or as safe as we may
have believed at the time of entering into such relationship. Also, we
or others could identify safety, side effects or manufacturing
problems with our products after they are on the market. Our business
may be impacted by government investigations, litigation and products
liability claims. We depend on third parties for a significant portion
of our manufacturing capacity for the supply of certain of our current
and future products and limits on supply may constrain sales of
certain of our current products and product candidate development.
In addition, sales of our products are affected by the
reimbursement policies imposed by third-party payors, including
governments, private insurance plans and managed care providers and
may be affected by regulatory, clinical and guideline developments
domestic and international trends toward managed care and health care
cost containment as well as U.S. legislation affecting pharmaceutical
pricing and reimbursement. Government and others' regulations and
reimbursement policies may affect the development, usage and pricing
of our products. In addition, we compete with other companies with
respect to some of our marketed products as well as for the discovery
and development of new products. We believe that some of our newer
products, product candidates or new indications for existing products,
may face competition when and as they are approved and marketed. Our
products may compete against products that have lower prices,
established reimbursement, superior performance, are easier to
administer, or that are otherwise competitive with our products. In
addition, while we routinely obtain patents for our products and
technology, the protection offered by our patents and patent
applications may be challenged, invalidated or circumvented by our
competitors and there can be no guarantee of our ability to obtain or
maintain patent protection for our products or product candidates. We
cannot guarantee that we will be able to produce commercially
successful products or maintain the commercial success of our existing
products. Our stock price may be affected by actual or perceived
market opportunity, competitive position, and success or failure of
our products or product candidates. Further, the discovery of
significant problems with a product similar to one of our products
that implicate an entire class of products could have a material
adverse effect on sales of the affected products and on our business
and results of operations.
The scientific information discussed in this news release related
to our product candidates is preliminary and investigative. Such
product candidates are not approved by the U.S. Food and Drug
Administration (FDA), and no conclusions can or should be drawn
regarding the safety or effectiveness of the product candidates. Only
the FDA can determine whether the product candidates are safe and
effective for the use(s) being investigated. Further, the scientific
information discussed in this news release relating to new indications
for our products is preliminary and investigative and is not part of
the labeling approved by the FDA for the products. The products are
not approved for the investigational use(s) discussed in this news
release, and no conclusions can or should be drawn regarding the
safety or effectiveness of the products for these uses. Only the FDA
can determine whether the products are safe and effective for these
uses. Healthcare professionals should refer to and rely upon the
FDA-approved labeling for the products, and not the information
discussed in this news release.
CONTACT: Amgen, Thousand Oaks
Christine Regan, 617-359-1324 (media)
Arvind Sood, 805-447-1060 (investors)
SOURCE: Amgen
http://explore.georgetown.edu/news/?ID=32887
| FOR IMMEDIATE RELEASE: April 13, 2008 |
|
| CONTACT: | Karen Mallet 414-312-7085 km463@georgetown.edu |
 |
|
In Lab Study,
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SAN DIEGO – Researchers at Georgetown University Medical Center have found a small molecule they say can block the action of the oncogene that causes Ewing’s sarcoma, a rare cancer found in children and young adults. If further studies continue to prove beneficial, they say the novel agent could be the first targeted therapy to treat the disease, which can produce tumors anywhere in the body. The findings, presented today at the annual meeting of the “I think this holds really wonderful promise as a unique way of This study was conducted in laboratory cells, so additional research is Ewing’s sarcoma is caused by the exchange of DNA between two In the United States, about 500 patients annually are diagnosed with the Toretsky has long led research into the causes of, and treatments for, They found that, indeed, the fusion protein stuck to another protein, The researchers used a laboratory technique to keep RHA apart from the Using a library of small molecules loaned to Georgetown from the This was a wonderful discovery, Erkizan says, because the notion long “These are wiggly proteins yet this study shows that inhibition of Toretsky recently received a The study was funded by the About Lombardi Comprehensive Cancer Center About Georgetown University Medical Center ### |
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http://www.pharmamar.com/en/press/news_release.cfm?newsReleaseID=178&year=2008
17 March 2008
Yondelis is being commercialized in the European Union for the treatment of advanced soft tissue sarcoma in adults.
Madrid,
March 17th, 2008: PharmaMar announces the initiation of a Phase II
multicenter study of Yondelis® (trabectedin) in children with recurrent
rhabdomyosarcoma, Ewing´s sarcoma, or non-rhabdomyosarcomatous soft
tissue sarcomas.
The study will determine a safe and tolerable
dose of Yondelis in pediatric patients and assess the efficacy at that
dose based on response rates. Additionally, toxicity and
pharmacokinetics in these patients will be determined. A total of 60
patients aged 12 months to 21 years old will be accrued within
approximately 2 years. Yondelis® will be administered as an intravenous
infusion for 24 hours every 3 weeks.
The study is being carried
out by the Childrens Oncology Group (COG) in centers of the USA and
Canada. COG is an international research group with more than 200
hospitals that treat children with cancer in the United States, Canada,
Australia, and Switzerland. The study is being managed by our
co-development partner, Johnson & Johnson Pharmaceutical Research
& Development, L.L.C.
The COG carried out a Phase I clinical
trial to determine Yondelis® dose-limiting toxicities and maximum
tolerated dose in children with refractory solid tumors, establishing
the recommended dose for pediatric phase II trials, and characterizing
the pharmacokinetics of Yondelis® in children. The study, published in
Clinical Cancer Research in 2005 determined that Yondelis® is safe in
children (Clinical Cancer Research Vol. 11, 672-677, Jan 2005).
Sylvain
Baruchel, MD., Director of the New Agent and Innovative Therapy Program
of the Hospital for Sick Children in Toronto, Canada, is the principal
investigator of the current study and the already completed Phase I.
PharmaMar
is committed to increasing the availability of medicines for children
through promoting the pediatric development of its pipeline when
appropriate. In line with this approach PharmaMar is planning to start
new pediatric studies in the future.
Yondelis® is currently
being developed by PharmaMar in partnership with Johnson & Johnson
Pharmaceutical Research & Development L.L.C.. According to the
licensing agreement, PharmaMar will market Yondelis® in Europe
(including Eastern Europe) while Ortho Biotech Products, L.P., will
market it in the U.S., and Janssen-Cilag will market it in the rest of
the world.
About soft tissue sarcomas in children*
Soft
tissue sarcomas are a heterogeneous group of malignancies of
mesenchymal origin that develop at a variety of primary sites
throughout the body. In children, soft tissue sarcomas generally are
classified as either rhabdomyosarcomas (RMS) or non-rhabdomyosarcomas
(non-RMS), with the non-RMS being further divided into multiple
histologic subtypes which also include Ewing´s sarcoma.
Rhabdomyosarcoma is the most common soft tissue sarcoma among children
0-14 years, representing nearly 50% of soft tissue sarcomas for this
age range with an incidence rate of 4.6 per million.
According
to the United States National Cancer Institute the incidence of soft
tissue sarcomas in children and adolescents younger than 20 years of
age was 11.0 per million, representing 7.4% of cancer cases for this
age group.
*Source: National Cancer Institute, Surveillance
Epidemiology and End Results (SEER) Cancer Incidence and Survival Among
Children and Adolescents: United States SEER Program 1975-1995. ICCC
IX, Soft Tissue Sarcomas. National Cancer Institute SEER Pediatric
Monograph.
Important note
PharmaMar, based in Madrid,
Spain, is a subsidiary of Grupo Zeltia (Spanish Stock Exchange, ZEL)
that is quoted in the Spanish Stock Exchange since 1963 and the Spanish
continuous market since 1998. Grupo Zeltia is currently part of the
Ibex Nuevo Mercado (New Market).
This document is a press
release, not a brochure. This document does not constitute nor is part
of any offer or invitation to sell or issue any application of
purchase, offer or shares subscription of the Society.
Likewise,
this document nor its distribution is part or can be of base for any
contract or investment decision and does not constitute any kind of
recommendation in relation with the shares of the Company.
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For more information: www.pharmamar.com
http://www.imclone.com/news.php
NEW YORK, Mar 05, 2008 (BUSINESSWIRE)– ImClone Systems Incorporated (NASDAQ: IMCL), a global leader in
the development and commercialization of novel antibodies to treat
cancer, today announced that the initial stage of a series of Phase
I/II clinical trials of IMC-A12, its anti-insulin-like growth factor-1
receptor (IGF-1R) monoclonal antibody, in children with relapsed or
refractory solid malignancies, has commenced patient enrollment. These
pediatric trials of IMC-A12 are being carried out by the Children's
Oncology Group (COG), an international research group that consists of
more than 240 centers that treat children and adolescents with cancer
in the United States, Canada, and other countries.
This study is the first of an initial stage of at least 10 Phase I
and II clinical trials of IMC-A12 sponsored by the Cancer Therapy
Evaluation Program (CTEP) of the Division of Cancer Treatment and
Diagnosis (DCTD), National Cancer Institute (NCI), to commence patient
enrollment. ImClone announced the selection of these proposals by NCI
in September 2007.
The insulin-like growth factor (IGF) system plays a critical role
in the development and progression of many types of cancer, including
many pediatric-specific cancers. The initial Phase I study, which will
be performed by the COG Phase I Consortium that includes 20 clinical
COG sites in North America, will determine the optimal dose, side
effects, pharmacology, and biological effects of IMC-A12 administered
intravenously once each week to children and adolescents with relapsed
or refractory solid cancers. Up to 38 patients are expected to be
enrolled. Immediately upon determination of a recommended pediatric
Phase II dose for IMC-A12, the antitumor activity of IMC-A12 will be
evaluated in a much larger Phase II study in a larger number of COG
sites. The Phase II study will evaluate the antitumor activity of
IMC-A12 in multiple pediatric malignancies, including osteosarcoma,
Ewing's sarcoma/peripheral primitive neuroectodermal tumor (PNET),
rhabdomyosarcoma, Wilms' tumor, and others.
“We are pleased to initiate the first of a series of NCI-sponsored
IMC-A12 trials and are particularly excited about this pediatric
study, as it is one of the first such studies of an IGF-IR inhibitor
ever undertaken in pediatric patients with cancer,” said Eric K.
Rowinsky, M.D., Chief Medical Officer and Executive Vice President of
ImClone Systems. “Evaluations of new cancer therapies in children
usually occur long after studies in adults and it is very gratifying
to begin directed studies of IMC-A12 in both adult and pediatric
patients at nearly the same time.”
IMC-A12 is a fully human IgG1 monoclonal antibody. It is designed
to specifically target the human IGF-1R, thereby inhibiting certain
ligands known as IGFs I and II from binding to and activating the
receptor. This action blocks a signaling pathway that enhances tumor
cell proliferation and survival. In 2007, ImClone completed enrollment
into two Phase I studies of IMC-A12, which demonstrated favorable
safety and pharmacokinetic profiles, as well as preliminary evidence
of antitumor activity as a single agent when administered either
weekly or every two weeks. In addition to the studies of IMC-A12 in
pediatric patients with advanced malignancies, Phase II studies of
IMC-A12 in patients with advanced prostate and colorectal cancers have
begun to enroll patients.
About ImClone's NCI-sponsored IMC-A12 Trials
In September 2007, the CTEP of the DCTD, NCI selected 10 proposals
for Phase I and II clinical trials of ImClone's IMC-A12, and several
other proposals have been selected since that time. The selection of
the proposed trials followed NCI's solicitation for specific
disease-directed studies among NCI investigators at academic
institutions, clinical trial consortia and NCI-sponsored oncology
cooperative clinical trial groups in the U.S. The selected trials
represent the first stage of clinical evaluations of IMC-A12 sponsored
by CTEP, NCI under a Clinical Trials Agreement between ImClone Systems
and DCTD, NCI to facilitate the clinical development of IMC-A12. Both
randomized and nonrandomized Phase II trials sponsored by CTEP will
explore the clinical activity, pharmacology and biological effects of
IMC-A12 as a single agent or combined with other relevant anticancer
agents in a wide range of malignancies including breast, lung,
pancreas and liver cancers, as well as both adult and pediatric
sarcomas. In addition, Phase I/II studies will evaluate the safety,
pharmacology, anticancer activity and biological effects of IMC-A12 in
children and adolescents with cancer, as well as in combination with
other novel targeting agents in which there is a specific rationale
for combined use.
About ImClone Systems
ImClone Systems Incorporated is a fully integrated
biopharmaceutical company committed to advancing oncology care by
developing and commercializing a portfolio of targeted biologic
treatments designed to address the medical needs of patients with a
variety of cancers. The Company's research and development programs
include growth factor blockers and angiogenesis inhibitors. ImClone
Systems' headquarters and research operations are located in New York
City, with additional administration and manufacturing facilities in
Branchburg, New Jersey. For more information about ImClone Systems,
please visit the Company's web site at
Certain matters discussed in this news release may constitute
forward-looking statements within the meaning of the Private
Securities Litigation Reform Act of 1995 and the Federal securities
laws. Although the company believes that the expectations reflected in
such forward-looking statements are based upon reasonable assumptions
it can give no assurance that its expectations will be achieved.
Forward-looking information is subject to certain risks, trends and
uncertainties that could cause actual results to differ materially
from those currently expected. Many of these factors are beyond the
company's ability to control or predict. Important factors that may
cause actual results to differ materially and could impact the company
and the statements contained in this news release can be found in the
company's filings with the Securities and Exchange Commission,
particularly those factors identified as “risk factors” in the
Company's most recent annual report of Form 10-K and in its quarterly
reports on Form 10-Q and current reports on Form 8-K. For
forward-looking statements in this news release, the company claims
the protection of the safe harbor for forward-looking statements
contained in the Private Securities Litigation Reform Act of 1995. The
company assumes no obligation to update or supplement any
forward-looking statements whether as a result of new information,
future events or otherwise.
SOURCE: ImClone Systems Incorporated
ImClone Systems Incorporated
Corporate Communications
Tracy Henrikson, 908-243-9945
MEDIA@IMCLONE.COM
or
Rebecca Gregory, 646-638-5058
Corporate Communications