Cytogen Corporation
(Nasdaq: CYTO) today announced interim results from a phase I clinical
trial of QUADRAMET(R) (samarium Sm-153 lexidronam injection) in combination
with bortezomib (Velcade(R), Millennium Pharmaceuticals, Inc.) in patients
whose multiple myeloma has relapsed following prior treatment. Data from
the ongoing study indicate that the combination regimen, known as VELSAM,
was well tolerated at doses studied to date and demonstrated anti-tumor
activity, with fifty percent of patients experiencing a response or
achieving stable disease. Results were presented at the 11th Congress of
European Hematology, organized by the European Hematology Association
(EHA).
"As we gain additional experience with patients receiving multiple
cycles of treatment, we continue to be impressed not only by the responses
observed in this heavily pretreated population of patients but also by the
patient friendly nature of this treatment regimen," said principal
investigator James Berenson, M.D., Medical & Scientific Director of the
Institute for Myeloma & Bone Cancer Research in West Hollywood, California.
The study involves patients with multiple myeloma whose disease has
progressed or is refractory to prior therapy and is designed to examine the
safety, tolerability, efficacy and anti-tumor effects of QUADRAMET in
combination with bortezomib. A treatment cycle consists of injections of
bortezomib on days one, four, eight and eleven with a single dose of
QUADRAMET administered on day three. No additional injections of bortezomib
or QUADRAMET are given for eight weeks. Patients may receive up to four
cycles of study treatment.
By way of comparison, bortezomib monotherapy is typically administered
on days one, four, eight and eleven of a treatment cycle that is repeated
every three weeks, typically for six to eight cycles.
The data reported was from twelve patients in four separate dose groups
who have completed at least one eight week cycle of VELSAM treatment. There
are two arms to the study: Arm one with bortezomib at 1.0 mg/m2 and Arm two
with bortezomib at 1.3 mg/m2. Both arms use escalating doses of QUADRAMET
(0.25 mCi/kg, 0.5 mCi/kg, and 1.0 mCi/kg). Patients are enrolled
alternately into parallel cohorts.
Responses are assessed using Blade criteria - a rigorous assessment
standard used to describe changes in disease status, including a
confirmation six weeks later. A "complete response" required 100 percent
disappearance of M-protein (a marker of tumor burden); negative
immunofixation testing; less than five percent plasma cells in the bone
marrow; no increase in size or number of lytic bone lesions; and
disappearance of soft tissue tumors (plasmacytomas). "Partial" remissions
and "minimal" responses represented lesser degrees of response based on the
same criteria. Worsening of these indicators constituted "progressive
disease."
The poster presentation (Poster # 738, Abstract # 1222) titled "Phase I
Study of Bortezomib and 153Sm-lexidronam Combination for Refractory and
Relapsed Multiple Myeloma" was presented at the EHA meeting during a
session titled "myeloma and other monoclonal gammopathies III" and reported
the following results:
- Twelve patients have been treated thus far at QUADRAMET doses of 0.25
and 0.5 mCi/kg. The standard approved dose of QUADRAMET for palliation
of bone pain is 1.0 mCi/kg;
- Patients had progressive disease despite receiving an average of 3.5
prior treatment regimens (median 3, range 1-8) for their myeloma and
eight of the twelve had relapsed following prior treatment with
bortezomib;
- Two patients received more than one VELSAM treatment cycle;
- One patient who received 0.5 mCi/kg of QUADRAMET and 1.0 mg/m2 of
bortezomib achieved a complete response and another who received 0.25
mCi/kg of QUADRAMET and 1.3 mg/m2 of bortezomib achieved a partial
response as defined by Blade criteria;
- Four additional patients, including all three who received 0.5 mCi/kg
of QUADRAMET and 1.3 mg/m2 of bortezomib achieved a stabilization of
their disease;
- Of the six patients that experienced a response or achieved stable
disease, three had previously failed treatment with bortezomib alone;
and
- Toxicities have generally been transient and manageable.
"We are pleased with the progress of this study and the interim results
reported in this poster presentation," said William Goeckeler, Ph.D.,
senior vice president of operations at Cytogen and co-author of the
presentation. "Patients are receiving additional treatment cycles and the
study continues to rapidly accrue patients at higher QUADRAMET dose levels.
We look forward to reporting additional results at scientific meetings
later this year."
About Multiple Myeloma
Multiple myeloma is a cancer of the bone marrow in which white blood
cells called plasma cells, normally responsible for the production of
antibodies (proteins that fight infection and disease), are overproduced.
The proliferation of these abnormal plasma cells, known as myeloma cells,
causes decreased production of normal red and white blood cells, and of
normal disease-fighting antibodies, as well as the growth of tumors that
spread to multiple sites - hence the term multiple myeloma. The decreased
white blood cell production damages the immune system while the myeloma
tumors cause bone destruction that manifests as pain and fractures.
The American Cancer Society estimates that about 16,570 new cases of
multiple myeloma (9,250 in men and 7,320 in women) will be diagnosed during
2006. About 11,310 Americans (5,680 men and 5,630 women) are expected to
die of multiple myeloma in 2006. The 5-year relative survival rate for
multiple myeloma is approximately 32%.
Standard treatment is with corticosteroids, thalidomide, alkylating
agents and stem cell transplantation. Multiple myeloma is highly
radiosensitive and is locally radiocurable. Novel systemic
radionuclide-based therapies may therefore provide a significant advance in
clinical therapy of myeloma.
About QUADRAMET
QUADRAMET is indicated for the relief of pain in patients with
confirmed osteoblastic metastatic bone lesions that enhance on radionuclide
bone scan. This press release describes clinical applications that differ
from that reported in the QUADRAMET package insert.
QUADRAMET is an oncology product indicated for pain relief that pairs
the targeting ability of a small molecule, bone-seeking phosphonate (EDTMP)
with the therapeutic potential of radiation (samarium Sm-153). Skeletal
invasion by prostate, breast, multiple myeloma, and other cancers often
creates an imbalance between the normal process of bone destruction and
formation. QUADRAMET selectively targets such sites of imbalance, thereby
delivering radioactivity to areas of the skeleton that have been invaded by
metastatic tumor.
QUADRAMET has demonstrated a range of characteristics that may be
advantageous for the treatment of pain arising from metastatic bone
disease, including early onset of pain relief (patients may experience pain
relief within the first week with maximal relief generally occurring at
three to four weeks after injection), predictable and reversible bone
marrow toxicity or myelosuppression that tends to return to pretreatment
levels after eight weeks, ease of administration, and length of pain
relief, lasting an average of four months in responding patients. QUADRAMET
is administered as a single intravenous injection, usually on an outpatient
basis, and exhibits selective uptake in areas of bone formation with little
or no detectable accumulation in soft tissue.
QUADRAMET Safety Profile
QUADRAMET causes bone marrow suppression. In clinical trials, white
blood cell counts and platelet counts decreased to a nadir of approximately
40% to 50% of baseline in 123 (95%) of patients within 3 to 5 weeks after
QUADRAMET, and tended to return to pretreatment levels by 8 weeks. Because
of the unknown potential for additive effects on bone marrow, QUADRAMET
should not be given concurrently with chemotherapy or external beam
radiation therapy unless the clinical benefits outweigh the risks. Blood
counts should be monitored weekly for at least 8 weeks, or until recovery
of adequate bone marrow function. Non-hematologic adverse events that
occurred in 5% or more of patients and greater than placebo were plain
flare (7%), diarrhea (6%), infection (7%), spinal cord compression (6.5%),
arrhythmias (5%), and hematuria (5%). Patients who receive QUADRAMET should
be advised that for several hours following administration, radioactivity
will be present in excreted urine. To help protect themselves and others in
their environment, precautions need to be taken for 12 hours following
administration.
A copy of the full prescribing information for QUADRAMET, including
warnings, precautions, adverse events and other safety information, may be
obtained in the U.S. from Cytogen Corporation by calling toll free 800-833-
3533 or by visiting the web site at cytogen which is not part of
this press release.
ABOUT CYTOGEN CORPORATION
Founded in 1980, Cytogen Corporation of Princeton, NJ, is a
biopharmaceutical company dedicated to improving the lives of patients with
cancer by acquiring, developing and commercializing innovative molecules
targeting the sites and stages of cancer progression. Cytogen's marketed
products include QUADRAMET(R) (samarium Sm-153 lexidronam injection),
PROSTASCINT(R) (capromab pendetide) kit for the preparation of Indium
In-111 capromab pendetide, and SOLTAMOX(TM) (tamoxifen citrate, oral
solution 10mg/5mL) in the United States. Cytogen's development pipeline
consists of CYT-500, a therapeutic radiolabeled antibody targeting
prostate-specific membrane antigen (PSMA), a protein highly expressed on
the surface of prostate cancer cells and the neovasculature of solid
tumors. Cytogen also has exclusive United States marketing rights to
COMBIDEX(R) (ferumoxtran-10) for all applications, and the exclusive right
to market and sell ferumoxytol (previously Code 7228) for oncology
applications in the United States. Full prescribing information for the
Company's products is available at cytogen. For more information, please visit the Company's website at
cytogen, which is not part of this press release.
This press release contains certain "forward-looking" statements within
the meaning of the Private Securities Litigation Reform Act of 1995 and
Section 21E of the Securities Exchange Act of 1934, as amended. All
statements, other than statements of historical facts, included in this
press release regarding our strategy, future operations, financial
position, future revenues, projected costs, prospects, plans and objectives
of management are forward-looking statements. Such forward-looking
statements involve a number of risks and uncertainties and investors are
cautioned not to put any undue reliance on any forward-looking statement.
There are a number of important factors that could cause Cytogen's results
to differ materially from those indicated by such forward-looking
statements. In particular, Cytogen's business is subject to a number of
significant risks, which include, but are not limited to: the risk of
obtaining the necessary regulatory approvals; the risk of whether products
result from development activities; the risk of shifts in the regulatory
environment affecting sales of Cytogen's products such as third-party payor
reimbursement issues; the risk associated with Cytogen's dependence on its
partners for development of certain projects, as well as other factors
expressed from time to time in Cytogen's periodic filings with the
Securities and Exchange Commission (the "SEC"). As a result, this press
release should be read in conjunction with Cytogen's periodic filings with
the SEC. The forward-looking statements contained herein are made only as
of the date of this press release, and Cytogen undertakes no obligation to
publicly update such forward-looking statements to reflect subsequent
events or circumstances.
cvt/
Cytogen Corporation
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