PRINCETON, N.J., Dec. 11 /PRNewswire-FirstCall/ -- Cytogen Corporation reported the presentation of updated data from an ongoing Phase 1 dose escalation study evaluating QUADRAMET(R) (samarium Sm-153 lexidronam injection) in combination with bortezomib (Velcade(R), Millennium Pharmaceuticals, Inc.) in patients with relapsed multiple myeloma. Data from 20 patients were presented during a poster session at the 48th Annual Meeting of the American Society of Hematology (ASH) in Orlando, Florida. Results indicated that the combination of QUADRAMET and bortezomib was well-tolerated at the doses studied.
The primary objective of the Phase 1 dose escalation study was to determine safety and tolerability of the combination regimen for patients with relapsed or refractory multiple myeloma. As a secondary objective, the study is also assessing response rates.
A complete treatment cycle is eight weeks in duration and consists of injections of bortezomib on days one, four, eight and eleven with a single dose of QUADRAMET administered on day three. 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.
There are two parallel arms to the study. The first arm administers bortezomib at 1.0 mg/m2 and the second arm administers 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). The standard approved dose of QUADRAMET for palliation of bone pain is 1.0 mCi/kg. Patients are enrolled alternately into parallel cohorts.
The poster presentation (Abstract # 3544) titled "Phase I Study of Bortezomib and 153Sm-lexidronam Combination for Refractory and Relapsed Multiple Myeloma" was presented at the ASH meeting during a session titled "Myeloma: Bortezomib-Based Therapies." A summary of the poster is as follows:
-- The study has enrolled twenty patients who failed two or more prior treatments, including previous treatment with bortezomib, with eighteen patients currently evaluable for disease response. -- Patients had progressive disease despite receiving an average of 3.5 prior treatment regimens (median 3, range 1-8) for their myeloma and twelve of the twenty had relapsed following prior treatment with bortezomib. -- Of 18 evaluable patients, seven have received more than one treatment cycle. -- Two patients have achieved a complete response, one who received two cycles of treatment and one who received four cycles of treatment. -- One patient who received four treatment cycles has achieved a minor response. -- Four patients have maintained stabilization of their disease, two who received two treatment cycles, one who received three treatment cycles, and one who received four treatment cycles. -- Of the seven patients who achieved a response or stable disease, three had previously failed treatment with bortezomib alone. -- Toxicities were generally transient and manageable, with only one instance of dose-limiting toxicity (DLT) which occurred in the cohort of patients who received 1.0 mCi/kg of QUADRAMET and 1.0 mg/m2 of bortezomib. Expansion of this cohort from three to six patients following the occurrence of the DLT (as required by the protocol) resulted in no additional DLTs. -- Preparations are underway for a follow-up Phase 2 study to further evaluate the efficacy and safety of QUADRAMET and bortezomib.
Responses were 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; 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".
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 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), length of pain relief, lasting a median of four months in responding patients, and predictable and reversible bone marrow toxicity or myelosuppression that tends to return to pretreatment levels after eight weeks. 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.
Cytogen is focused on advancing numerous initiatives designed to maximize the near- and long-term growth potential of QUADRAMET. Key examples include: (i) identifying new ways to distinguish QUADRAMET from first-generation agents within its class; (ii) generating awareness of QUADRAMET's utility for the palliation of pain among key oncology prescribing audiences; (iii) broadening the product's palliative use within label through data-driven initiatives; (iv) generating safety data for QUADRAMET in combination with other commonly used oncology agents; and (v) evaluating the potential tumoricidal versus palliative attributes of QUADRAMET.
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.
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 Cytogen
Founded in 1980, Cytogen is a biopharmaceutical company dedicated to advancing the care of cancer patients by building, developing, and commercializing a portfolio of specialty pharmaceutical products. The Company's specialized sales force currently markets QUADRAMET(R), PROSTASCINT(R), and SOLTAMOX(TM) to the U.S. oncology market. QUADRAMET is approved for the treatment of pain in patients whose cancer has spread to the bone, PROSTASCINT is a PSMA-targeting monoclonal antibody-based agent to image the extent and spread of prostate cancer, and SOLTAMOX is the first liquid hormonal therapy approved in the U.S. for the treatment of breast cancer in adjuvant and metastatic settings. In early 2007, Cytogen plans to introduce its fourth approved oncology product to the U.S. market, CAPHOSOL(R), a prescription medical device for the treatment of oral mucositis and dry mouth. The Company is also developing CYT-500, a third-generation radiolabeled antibody to treat prostate cancer. Cytogen's product-focused strategy focuses on attaining sustainable growth through clinical, commercial, and strategic initiatives.
A copy of the full prescribing information for CAPHOSOL, QUADRAMET, PROSTASCINT, and SOLTAMOX, including box warnings, may be obtained in the U.S. from Cytogen Corporation by calling toll free 800-833-3533 or by visiting Cytogen's web site at http://www.cytogen.com. The Company's website 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.
Cytogen CorporationCONTACT: Media/Investors: Susan M. Mesco of Cytogen Corporation, +1-609-750-8213
Web site: http://www.cytogen.com/
