New Clinical Data for Prostascint and Quadramet in Prostate Cancer Presented at the 2007 Prostate Cancer Symposium
"The multiple presentations for both PROSTASCINT and QUADRAMET are part of our data-driven strategy to realize the full and untapped market opportunity for these products within their current indications," said Michael D. Becker, president and chief executive officer of Cytogen Corporation. "The data also highlight future growth opportunities and will help us learn more about their potential role in the improvement of cancer outcomes."
Cytogen's PROSTASCINT molecular imaging agent is the first and only commercial product targeting prostate-specific membrane antigen or PSMA. PSMA is a protein abundantly expressed on the surface of prostate cancer cells, with an increased expression in high-grade cancers, metastatic disease and hormone-refractory prostate cancer. PROSTASCINT consists of a proprietary PSMA-targeting monoclonal antibody, 7E11-C5, linked to the imaging radioisotope Indium-111. By targeting PSMA, the PROSTASCINT molecular imaging procedure can detect the extent and spread of prostate cancer using a standard gamma camera. PROSTASCINT was featured in six presentations that are summarized below.
"Eight-year biochemical disease free survival following permanent prostate brachytherapy with dose escalation in biologic target volumes identified with SPECT/CT capromab pendetide" (Abstract No. 357)
One of the two outcomes studies presented related to eight-year survival outcomes data from a prospective, comparative clinical trial using PROSTASCINT fusion imaging. The study utilized PROSTASCINT fusion imaging to assess local and distant disease and to alter the radiation dose to areas of suspected high tumor burden to enable more efficient and precise targeting of brachytherapy. PROSTASCINT fusion imaging combines anatomical images from computed tomography (CT) or magnetic resonance imaging (MRI) with functional images from single-photon emission computed tomography (SPECT) using PROSTASCINT. Data from the study indicate that individualizing seed implantation regimens results in high rates of biochemical disease free survival (bDFS) in these patients. Importantly, patients whose PROSTASCINT fusion image showed their cancer to be limited to the prostate gland had significantly higher rates of bDFS than those whose image showed uptake outside the prostate.
"PROSTASCINT brings a new level of precision to prostate cancer imaging by providing a clearer view of the location and extent of disease in and around the prostate," said Rodney J. Ellis, M.D., a radiation oncologist and assistant professor of urology with the Case School of Medicine, and the lead investigator in the study. "Beyond its approved indication in imaging disease, by visualizing the tumor within the prostate gland, PROSTASCINT may help determine where to deliver the highest doses of radiotherapy to individual patients -- increasing the chances of disease-free survival while attempting to limit treatment-related side effects," added Dr. Ellis.
The study evaluated the use of PROSTASCINT fusion imaging to define brachytherapy treatment regimens for 239 newly-diagnosed prostate cancer patients. It utilized two sets of criteria for evaluating biochemical failure: the standard ASTRO consensus criteria and the newer Radiation Therapy Oncology Group (RTOG)-ASTRO Phoenix Consensus Conference definition. Overall, the eight-year bDFS rate was 88.2% using the ASTRO criteria and 82.5% by the Phoenix definition. PROSTASCINT findings of prostate-confined disease correlated with bDFS rates of 91.7%, while patients with periprostatic (near the prostate) and distant disease had bDFS rates of 72.7% and 66.7% by ASTRO criteria (p = 0.0003); the corresponding rates by Phoenix criteria were 86.6%, 71.6% and 56.8% (p less than 0.0001). When stratified according to low, intermediate and high risk groups, bDFS rates were 96.1%, 86.0% and 74.2% by ASTRO and 89.8%, 84.1% and 66.2% by Phoenix criteria, respectively.
Prostate brachytherapy employs the implantation of radioactive seeds into the prostate. Brachytherapy can deliver high doses of radiation to the prostate while limiting the radiation exposure to the adjacent organs. Image-guided brachytherapy alone and in combination with external beam radiation is a first-line therapy for patients with localized prostate cancer.
"Prediction of prognosis for prostate cancer patients with central abdominal uptake on capromab pendetide (PROSTASCINT)" (Abstract No. 173)
The second outcomes study investigated patients whose PROSTASCINT images showed uptake in the central abdomen as compared to those without such findings. Central abdominal uptake (CAU) of PROSTASCINT is difficult to confirm pathologically; therefore, outcomes in patients with this finding are important. In the study of 341 men with prostate cancer who underwent PROSTASCINT imaging, PROSTASCINT detected CAU in 69 or 20% of the patients. Patients were followed for a median of four years and prostate cancer-specific death rates were 10 times greater in the CAU group (p=0.005). Furthermore, the increased death rates were independent of the use or timing of intervention with hormone therapy.
"Although there has been uncertainty about the meaning of central abdominal activity on these scans, most physicians experienced in the use of PROSTASCINT believe that this multifocal abdominal pattern represents metastatic disease in retroperitoneal and/or mesenteric lymph nodes," said Michael Manyak, M.D., vice president of medical affairs with Cytogen. "This outcomes study is striking because, with limited existing histopathologic correlation, the data show that this pattern of uptake with PROSTASCINT is associated with a poor prognosis. This is now the third study to show a bad prognosis in patients with signal outside of the pelvis."
"The use of fused PROSTASCINT CT scans in planning IMRT for prostate cancer" (Abstract No. 363)
This study evaluated the value of PROSTASCINT fusion imaging to guide externally delivered intensity modulated radiation therapy (IMRT). In a Phase 2 trial of 71 men with prostate cancer, PROSTASCINT fusion imaging was used to deliver enhanced doses of radiation to regions of the prostate with the greatest tumor burden. Investigators reported that PROSTASCINT-guided IMRT led to "appropriate" responses in prostate-specific antigen (PSA) levels; bDFS rates were 98% at 24 months and 92% at 36 months. The authors concluded that the regimen was well tolerated and that the integration of newer imaging technology into radiotherapy planning should lead to improvements in the therapy of prostate cancer.
"Impact of capromab pendetide scanning in a selection of prostate cancer treatments compared to clinical risk factors alone" (Abstract No. 189)
The study was conducted to determine if PROSTASCINT imaging was of value in determining the extent of disease and guiding choice of treatment compared to clinical risk assessment alone. The trial enrolled 93 patients, divided into those at high risk (49) and those at low risk (44) for metastatic disease. Treatment outcomes were analyzed based on clinical risk assignment and PROSTASCINT scan result. Treatment failure was determined by failure of PSA to nadir and durability of response after treatment. The authors concluded that PROSTASCINT scans, in addition to clinical parameters, can more clearly define patients with local or metastatic disease, help clarify treatment decisions and prevent patient morbidity from unnecessary treatment.
The two investigator-sponsored studies noted below reported on response rates to salvage radiation therapy in patients with a rising PSA following radical prostatectomy. The pre-radiation evaluation for these patients included a PROSTASCINT image.
"Can the negative 111-indium-capromab pendetide scan predict outcome after salvage external beam radiotherapy?" (Abstract No. 188) and "Salvage RT after post-prostatectomy biochemical failure: Outcomes for patients with no extraprostatic disease with radioimmunoscintigraphy?" (Abstract No. 213)
In Abstract #188, which involved 49 patients, the authors reported a response rate of 88% at a median of three years follow-up, while in Abstract #213, which involved 42 patients, the corresponding rate was 62%. Both groups concluded that their findings required further study including among other things the effect of using fused PROSTASCINT images.
QUADRAMET is an oncology product for the treatment of pain arising from cancer that has spread to the bone. 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 was featured in two presentations that are summarized below.
"Phase 1 study of docetaxel and 153 Sm repetitively administered for castrate metastatic prostate cancer (CMPC)" (Abstract No. 231)
G.A. Gignac, M.D. and colleagues of Memorial Sloan-Kettering Cancer Center reported interim data from an ongoing Phase 1 trial. Dr. Gignac was honored by ASCO as a Merit Award recipient for her presentation, which included data from 18 patients with CMPC who received repeated escalating doses of the combination of QUADRAMET (at doses up to 1.0 mCi/kg given every six to nine weeks) and docetaxel (at doses up to 75 mg/m(2)given every three weeks). The authors concluded that repetitive dosing of QUADRAMET and docetaxel has been well tolerated and is feasible and that dose-limiting toxicity has not been reached. The study continues to accrue patients in a Phase 1 extension to explore the optimal dosing schedule for a Phase 2 clinical study, with the extension cohort using full FDA-approved doses of QUADRAMET (1.0 mCi/kg) and docetaxel (75 mg/m(2).)
"A Phase 2 trial of docetaxel and samarium 153-EDTMP in patients (pts) with bone metastases from castration-refractory prostate cancer (CRPC) with response or stabilization after induction docetaxel-estramustine" (Abstract No. 227)
In a prospective, Phase 2 investigator-sponsored trial investigators reported on long-term pain responses, disease progression and survival in patients treated with a combination of QUADRAMET and docetaxel/estramustine. Forty-three patients with CRPC were administered docetaxel (70 mg/m(2) per cycle) on three week intervals for three cycles which was followed by a weekly dosing schedule of docetaxel (20 mg/m(2) per cycle for six cycles) during which a single dose of QUADRAMET (1.0 mCi/kg) was administered in combination with the first dose of docetaxel. The authors reported a median time to progression of seven months and a median survival of approximately 30 months. In addition, in the majority of patients in this study who were symptomatic at baseline, with a median score of four on a ten point scale, very good long term pain control was reported with median pain scores of 1.0 and 0.5 at 12 and 18 months, respectively.
"The unique combination of nuclear, chemical and biologic properties of QUADRAMET result in a safety and efficacy profile that we believe will allow it to be combined with other agents commonly used in the treatment of cancer patients," said William Goeckeler, PhD, senior vice president of operations with Cytogen. "The data presented at this meeting demonstrate the tolerability of QUADRAMET when administered in combination with taxane-based chemotherapy in patients with prostate cancer and reaffirms our strategy of evaluating the use of QUADRAMET in combination with a variety of therapeutic agents not only in patients with prostate cancer but also in other cancers such as breast, multiple myeloma and osteosarcoma."
About Prostate Cancer
Prostate cancer is the most common type of cancer found in American men, other than skin cancer. In 2006, the American Cancer Society estimates that there will be about 234,000 new cases of prostate cancer in the United States and that about 27,000 men will die from the disease. It is estimated that there are more than 2 million American men currently living with prostate cancer. Bone metastases are a common complication of prostate cancer with estimates of incidence ranging from 65 to 75%.
Tests to determine the amount of prostate-specific antigen (PSA), a protein produced by the cells of the prostate gland, in the blood along with a digital rectal exam is used to help initially detect prostate cancer and is also used to monitor patients with a history of prostate cancer to see if the cancer has come back, or recurred. PSA levels cannot directly identify the extent or location of disease.
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) (samarium Sm-153 lexidronam injection), PROSTASCINT(R) (capromab pendetide), and SOLTAMOX(TM) (tamoxifen citrate) 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), an advanced electrolyte solution for the treatment of oral mucositis and dry mouth that is approved in the U.S. as a prescription medical device. 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.
This press release describes clinical applications that differ from those reported in the PROSTASCINT and QUADRAMET package inserts. A copy of the full prescribing information for PROSTASCINT and 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. 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 successfully marketing its products; 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. All information in this press release, including 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 this information to reflect subsequent events or circumstances.
Susan Mesco, 609-750-8213
JFK Communications, Inc.
John F. Kouten
Posted: February 2007