PRINCETON, N.J., June 19 /PRNewswire-FirstCall/ -- Cytogen Corporation 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).
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"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 www.cytogen.com, 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 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 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.
Media/Investors contact: Brian Korb The Trout Group (212) 477-9007 x23
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Web site: http://www.cytogen.com/
