PRINCETON, N.J., Dec. 12 /PRNewswire-FirstCall/ -- Cytogen Corporation announced today the presentation of preclinical data on its flagship product QUADRAMET(R) (samarium Sm-153 lexidronam) in combination with bortezomib (Velcade(R), Millennium Pharmaceuticals, Inc.). The combination demonstrated broad anti-cancer activity in a murine myeloma model including greatly prolonged median survival, rapidly reduced clonogenicity of bone- marrow resident 5TGM1 cells, slowed elevation of serum myeloma-associated paraprotein levels, and longer term preservation of bone mineral density.
Data from the new study was presented by researchers from the Mayo Clinic College of Medicine at the American Society of Hematology (ASH) 47th Annual Meeting and Exposition in a poster session on Myeloma: Therapy, Bone Disease, and Immunotherapy. The poster was titled “Synergistic Activity of the Proteasome Inhibitor PS-341 with Non-Myeloablative 153-Sm-EDTMP in a Syngeneic, Orthotopic Model of Multiple Myeloma.”
In vitro studies demonstrated synergistic killing of myeloma cell lines with the combination of QUADRAMET and bortezomib. In vivo studies demonstrated that the combination therapy greatly prolonged median survival of mice and was well tolerated. The preclinical study was conducted in a mouse model in which murine myeloma 5TGM1 cells are injected intravenously into syngeneic mice. This murine myeloma model exhibits changes in the skeleton that are reported to be indistinguishable from those seen in human patients and is used for studies of pathogenetic mechanisms in myeloma and for preclinical evaluation of novel anti-tumor strategies.
Poster Presentation Highlights: -- In vitro clonogenic assays performed using a panel of myeloma cell lines demonstrated synergistic killing following co-treatment with QUADRAMET and bortezomib. -- Using the 5TGM1 myeloma model, the median survivals of mice treated with saline, two doses of bortezomib (0.5 mg/kg), or a single non- myeloablative dose of QUADRAMET (22.5 MBq) were 21, 22 and 28 days, respectively. In contrast, mice treated with combination therapy comprising two doses of bortezomib (0.5 mg/kg) one day prior to and one day following QUADRAMET (22.5 MBq) showed a greatly prolonged median survival of 49 days. -- Correlative studies indicated that combination treatment with bortezomib and QUADRAMET rapidly reduced the clonogenicity of bone- marrow resident 5TGM1 cells, slowed the elevation of serum myeloma- associated paraprotein levels, and was associated with longer term preservation of bone mineral density as compared to single-agent therapy. -- The authors concluded that bortezomib is a potent in vivo radiosensitizer that greatly enhances the therapeutic potency of QUADRAMET in the syngeneic, orthotopic 5TGM1 myeloma model without increasing myelotoxicity.
Cytogen believes that these positive findings support clinical evaluation of QUADRAMET in the treatment of patients with multiple myeloma. Cytogen has already initiated Phase I clinical trials to evaluate treatment involving a combination of QUADRAMET plus bortezomib in patients with relapsed or treatment-refractory multiple myeloma. QUADRAMET is also currently being evaluated in multiple myeloma patients in a Phase I combination trial with zoledronic acid (Zometa(R), Novartis AG).
“The study results presented at this year’s annual meeting of the American Society of Hematology shows that treatment regimens incorporating QUADRAMET have significant activity in relevant pre-clinical models of multiple myeloma and underscores the clinical rationale for and the versatility of QUADRAMET with potential applications in treating a wide range of cancers,” said William Goeckeler, Ph.D., Senior Vice President of Operations at Cytogen. “The Mayo Clinic’s recent findings provide additional solid scientific support for expanding the clinical development of QUADRAMET beyond our current programs in solid tumors.”
About Multiple Myeloma
Multiple myeloma (also known as myeloma or plasma cell myeloma) is a cancer of the blood in which malignant plasma cells are overproduced in the bone marrow. Plasma cells are white blood cells that help produce antibodies called immunoglobulins that fight infection and disease. However, most patients with multiple myeloma have cells that produce a form of immunoglobulin called paraprotein (or M protein) that does not benefit the body. In addition, the malignant plasma cells replace normal plasma cells and other white blood cells important to the immune system. Multiple myeloma cells can also attach to other tissues of the body, such as bone, and produce tumors. The cause of the disease remains unknown.
Multiple myeloma is the second most common cancer of the blood, representing approximately one percent of all cancers and two percent of all cancer deaths with a reported worldwide prevalence of approximately 200,000 cases. In the year 2004, there were an estimated 74,000 new cases of multiple myeloma worldwide. The estimated number of deaths from multiple myeloma in 2005 is about 60,000 worldwide.
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 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 many characteristics that the company believes are 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, 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 bone 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 http://www.cytogen.com, which is not part of this press release.
About Bortezomib
Bortezomib, a drug in the proteasome inhibitor class of agents, is cytotoxic to a variety of cancer cell types in vitro. The proteasome pathway plays an essential role in regulating the intracellular concentration of specific proteins, thereby maintaining homeostasis within cells. Disruption of normal homeostatic mechanisms can lead to cell death.
Bortezomib also exhibits potent radiosensitizing capability that may be synergistic with QUADRAMET. For this reason, current and planned trials are exploring the optimal dose and schedule of administration of bortezomib with concurrent QUADRAMET radiotherapy.
ABOUT CYTOGEN CORPORATION
Founded in 1980, Cytogen Corporation of Princeton, NJ is a biopharmaceutical company that acquires, develops and commercializes innovative molecules targeting the sites and stages of cancer progression. Cytogen’s marketed products include QUADRAMET(R) (samarium Sm-153 lexidronam injection) and PROSTASCINT(R) (capromab pendetide) kit for the preparation of Indium In-111 capromab pendetide in the United States. 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. Cytogen’s development pipeline consists of therapeutics targeting prostate- specific membrane antigen (PSMA), a protein highly expressed on the surface of prostate cancer cells and the neovasculature of solid tumors. Full prescribing information for the Company’s products is available at www.cytogen.com or by calling 800-833-3533. For more information, please visit the Company’s website at www.cytogen.com, 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 additional capital; 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.
Cytogen Corporation
CONTACT: Media/Investors contact - Jonathan Fassberg, The Trout Group,+1-212-477-9007 x16, for Cytogen Corporation
Web site: http://www.cytogen.com/
