Healthcare Industry News: osteoporosis
News Release - June 7, 2006
Data Presented at SNM Meeting Demonstrate Novel Therapeutic Combinations and Applications for QUADRAMET(R)Data presented on QUADRAMET use in combination with chemotherapy and statins, as well as novel application in kyphoplasty
PRINCETON, N.J., June 7 (HSMN NewsFeed) -- Cytogen Corporation (Nasdaq: CYTO ) today announced the presentation of data from a series of investigator-sponsored studies of QUADRAMET® (samarium Sm-153 lexidronam injection) in a variety of therapeutic combinations and applications. Results were presented at the 53rd Society of Nuclear Medicine (SNM) annual meeting taking place this week in San Diego, California.
"These results from investigators around the world validate the current role of QUADRAMET for pain palliation and in novel combinations with chemotherapy for the treatment of metastatic bone disease, as well as in other unique applications," said Michael D. Becker, president and chief executive officer of Cytogen. "We will continue to build on the established role of QUADRAMET for the treatment of pain arising from metastatic bone disease while driving company-sponsored clinical development programs in other indications such as combination use with bortezomib, docetaxel and other potentially synergistic agents for the treatment of cancer."
Highlights of the four QUADRAMET abstracts presented at SNM include:
"Early response and toxicity of 153Sm-EDTMP combined with docetaxel in patients with hormone-refractory metastatic prostate cancer (Abstract 297)"
The objective of this phase II study sponsored by investigators from the University of Pisa (Italy) is to evaluate the safety and efficacy of QUADRAMET in combination with docetaxel in hormone refractory prostate cancer patients with bone metastases. Twenty-three patients received a single injection of QUADRAMET (1 mCi/kg) and then at least six cycles of docetaxel at a dose of 75 mg/m2 every three weeks beginning four to six weeks later.
The mean prostate-specific antigen (PSA) level for these patients was 105 ng/mL (median 171). Sixteen patients had more than ten metastatic bone lesions, four patients had three to nine metastatic bone lesions, and three patients had less than three metastatic bone lesions. Mean baseline pain score in this group was four, as defined by a ten-point pain visual analog scale (VAS). Eighteen of the twenty-three patients received more than six cycles and five patients received less than six cycles of docetaxel. Four patients received two doses of QUADRAMET.
Seventeen of the twenty-three patients demonstrated PSA declines (two patients with declines of greater than 50% and fifteen patients with a decline between 20% and 50%). Progression of disease was observed in sixteen of the twenty-three patients at a median of thirty-eight weeks after QUADRAMET. Data on overall survival are pending.
Grade three toxicity of platelets and white blood cells were each observed in one of the twenty-three patients following administration of QUADRAMET and the hematologic toxicity following the administration of docetaxel was similar to that seen when the agent is administered alone.
The investigators concluded that combination therapy with QUADRAMET and docetaxel was feasible and well-tolerated with good pain relief and promising rates of response and time to progression.
"Simvastatin therapy enhances therapeutic efficacy of samarium-153-EDTMP in prostate cancer patients with multiple bone metastases (Abstract 298)"
"Statins" are a class of drugs that lowers the level of cholesterol in the blood by reducing the production of cholesterol by the liver. Experimental data indicate that statins may also induce apoptosis and delay tumor growth. Investigators from the University of Vienna (Austria) and the University of Perugia (Italy) studied whether QUADRAMET might be more effective if statins are coadministered. Patients with multiple bone recurrences secondary to prostate cancer refractory to hormone treatment were treated with QUADRAMET according to the Vienna protocol (30 mCi) five times in three months intervals. One-hundred and fifty patients with simvastatin therapy (20 mg/d) were compared with one-hundred and eighty-eight patients without lipid lowering agents.
Pain palliation was higher (complete 50% vs. 45%, partial 43% vs. 39%, no relief 7% vs. 16%; p<0.01) in statin-treated patients. PSA decrease after first (32% vs. 18%), second (35% vs. 17%) and third (37% vs. 17%) QUADRAMET dose was also more frequently seen in statin users. QUADRAMET bone uptake (58.9% vs. 59.8%), flare phenomenon (4% vs. 5%) and hematological response (platelet, white and red blood cell count) did not differ. Subanalysis of patients not using statins with elevated versus normal total and LDL- cholesterol as well as CH/HDL-ratio revealed no difference as to therapeutic response or any of the biomarkers. The investigators concluded that concomitant statin therapy enhances the effect of conventional therapeutic strategies mainly via a non-lipid action and may thereby significantly delay disease progression.
"The use of local injection of 153Samarium-EDTMP in conjunction with kyphoplasty for palliation bone metastasis (Abstract 1794)"
The investigators from New York Methodist Hospital reported the intravertebral injection of QUADRAMET with kyphoplasty for palliative treatment of vertebral metastases to strengthen the vertebra along with extinguishing metastatic vertebral lesion with least myelosuppression, thus adding anticancer effect to the benefit of kyphoplasty. Six patients with documented vertebral bone metastasis were studied (Thoracic in one and lumbar spine in five). Primary cancer was lung (2), prostate (1), maxillary sinus (1), myeloma (1) and colon (1). Kyphoplasty procedure was carried out in the operating room using the known protocol of polymethylmethacrylate bone cement administration to which 1-2 mCi of QUADRAMET was added.
The first scan less than two hours following the procedure demonstrated radiotracer concentration in the injected lesion in all patients. The percentage of tracer activity in the vertebra was 73% to 76%. There was evidence of systemic absorption (24% - 27%). The absorbed radiotracer also targeted other skeletal metastatic lesions (ribs, other vertebrae and pelvic bone). One of six cases had follow up bone scans in two months and four months showed decreasing intensity of radiotracer uptake in the lesion of injected site (T10) as well as in a lesion away from injected site (right posterior ninth rib). There was consistent dramatic improvement of pain score in all patients. Significant myelosuppression did not occur in any patient. The investigators concluded that local QUADRAMET injection in conjunction with kyphoplasty may add an important treatment choice in patients with painful vertebral metastases with a potential for less myelosuppression.
Kyphoplasty is a minimally invasive treatment for spinal fractures caused by osteoporosis or cancer. The procedure consists of two small incisions and a probe placed into the vertebral space where the fracture is located. The bone is drilled and a balloon is inserted on each side. These balloons are then inflated until they expand to the desired height and removed. The spaces created by the balloons are then filled with orthopedic cement that hardens quickly, providing strength and stability to the vertebra, restoring height and relieving pain.
"Bone marrow scan to assess functional reserve and predict severity and duration of neutropenia and thrombocytopenia following Samarium-153 therapy (Abstract 1795)"
Researchers from The James A. Haley Veterans' Hospital in Tampa, Florida reviewed whether assessment of functional marrow reserve by diagnostic whole- body bone marrow scan (BMS) was a better predictor of patients who may develop more severe and/or prolonged neutropenia and thrombocytopenia than reliance only on baseline blood counts.
Twenty-five patients received 1 mCi/kg of QUADRAMET for treatment of metastatic prostate (n=23) or breast (n=2) cancer. There were twenty-four men and one woman, age 54 to 88 (mean 73) years. Average baseline white blood cell and platelet counts for all patients were 7.5k (range 3.5 to 16.9k) and 285k (range 101 to 489k), respectively. BMS was performed on each patient on average one week prior to therapy. Contrary to expected findings, there was no statistically significant correlation between the extent of bone marrow involvement and severity of neutropenia and/or thrombocytopenia.
In this small series, assessment of functional marrow reserve by BMS was of limited value in predicting which patient may experience significant neutropenia or thrombocytopenia following 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 http://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® (samarium Sm-153 lexidronam injection), PROSTASCINT® (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® (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 http://www.cytogen.com or by calling 800-833-3533. For more information, please visit the Company's website at http://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.
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