NEOPHARM Presents Updated CINTREDEKIN BESUDOTOX Phase I/II Median Survival Data at European Association of Neuro-Oncology (EANO) Meeting.WAUKEGAN, Ill. -- Deferred Catheter Positioning Provides a Statistically Significant Improvement in Achieving Optimal Catheter Placement NEOPHARM, Inc. (Nasdaq:NEOL) today announced that, based on long-term follow up data from its Phase I/II clinical studies, CINTREDEKIN BESUDOTOX (IL13-PE38QQR) continues to show evidence of prolonged overall survival in patients with recurrent glioblastoma multiforme glioblastoma mul·ti·for·me n. A virulent brain cancer that is usually fatal. (GBM GBM 1 Glioblastoma multiforme, see there 2. Glomerular basement membrane ). Specifically, updated survival data for GBM patients treated in the Company's Phase I/II studies and results from a subset analysis of these Phase I/II studies was presented in a scientific symposium on brain tumor Brain Tumor Definition A brain tumor is an abnormal growth of tissue in the brain. Unlike other tumors, brain tumors spread by local extension and rarely metastasize (spread) outside the brain. treatments at the annual meeting of the European Association of Neuro Oncology (EANO) meeting in Vienna, Austria on Saturday, September 16, 2006. Sandeep Kunwar, M.D., Associate Professor of Neurological Surgery, University of California, San Francisco (UCSF UCSF University of California at San Francisco ), and Principal Investigator of the Company's on-going Phase III PRECISE trial for CINTREDEKIN BESUDOTOX, presented updated data for the 45 GBM patients treated in the Phase I/II intraparenchymal setting in a scientific presentation entitled Advances in the Treatment of GBM: CED (Capacitance Electronic Disc) An earlier videodisc technology from RCA that was released in 1981 and abandoned five years later. Like phonograph records, the analog disc contained grooves that a stylus rode over. of CINTREDEKIN BESUDOTOX (IL13-PE38QQR). Overall median survival for these patients continued to be 44.0 weeks; however, median survival increased to 55.6 weeks for the 27 patients with two or more optimally placed catheters. Dr. Kunwar also indicated that an independent statistical analysis of the Phase I/II data confirmed that catheter placement was a key prognostic factor prognostic factor Medtalk Any factor–eg, Pt age, family Hx, lifestyle, stage of presentation, that is weighed in determining a prognosis. See Prognosis. related to prolonged survival. Furthermore, post-operative stereotactic stereotactic /ster·eo·tac·tic/ (-tak´tik) 1. characterized by precise positioning in space; said especially of discrete areas of the brain that control specific functions. 2. pertaining to stereotactic surgery. catheter placement, in which catheters are placed 2-4 days post-tumor resection, provided a statistically significant improvement (p=0.003) in achieving optimal catheter positioning (79% of deferred catheter placement (n=51) vs. 49% of intra-operative catheter placement (n=88)). The catheter placement guidelines developed during the Phase I/II clinical trial experience were incorporated by NEOPHARM into the design of the pivotal Phase III PRECISE trial of CINTREDEKIN BESUDOTOX in first recurrent GBM. Training physicians in the proper placement of catheters was an integral part of the PRECISE trial program.
Recurrent GBM Patients From Phase I/II Intraparenchymal Setting
(IL13PEI-002, 105 and 103R02)
Median Lower Upper One-Year Two-Year
Survival CI CI Survival Survival
(Weeks) (a) (a) (%) (%)
Overall (n=45) 44 36.1 55.6
(1) Optimal Catheter
Placement (n=27) 55.6 36.1 74.3 51.9 18.5
(1) Sub-Optimal Catheter
Placement (n=18) 38.4 29.0 45.9 22.2 5.6
Subset of Phase I/II (IL13PEI-002) Patients Treated at UCSF
Median Lower Upper
Survival CI CI
(Weeks) (a) (a)
Overall (n=22) 57.4 37.4 78.0
(1) Optimal Catheter
Placement (n=16) 69.9 37.6 98.6
(1) Sub-Optimal Catheter
Placement (n=6) 41.6 32.0 51.9
(1) = Catheter placement is an objective score system based on
catheter depth from brain surfaces including any intervening brain
structures along the catheter trajectory as well as proximity to
the tumor resection cavity.
(a) = Confidence Interval. Approaching significance by Log Rank Test
(p=0.081). Significant by Cox Proportional Hazards Model (p=0.004)
"These data are encouraging when you consider that median patient survival is approximately 28 weeks with currently available treatment options for recurrent GBM," said Dr. Kunwar. "Convection Enhanced Delivery of CINTREDEKIN BESUDOTOX represents a promising potential advancement in the treatment of GBM where we can selectively target the infiltrative tumor cells without damaging functional tissue. Importantly, post-operative catheter placement provides a significant improvement in optimizing catheter positioning, which appears to play an important role in drug distribution and patient outcomes." A copy of Dr. Kunwar's presentation is available on NEOPHARM's "Company Information\Abstracts" page of its corporate website at www.NEOPHARM.com. About Glioblastoma Multiforme Glioblastoma multiforme (GBM) is the most common type of malignant primary brain tumor primary brain tumor Neurology A tumor that arises in the brain–eg, ependymoma, astrocytoma grade 3 or 4, glioblastoma multiforme, glioma, medulloblastoma, meningioma, neuroglioma, oligodendroglioma. See Metastatic brain tumor. in adults. According to the Central Brain Tumor Registry of the United States (CBTRUS CBTRUS Central Brain Tumor Registry of the United States (Chicago, IL) , www.cbtrus.org), GBM tumors typically affect men more commonly than women, particularly men between the ages of 60 and 85 years. According to the CBTRUS, approximately 10,000 people are diagnosed annually with malignant glioma glioma /gli·o·ma/ (gli-o´mah) a tumor composed of neuroglia in any of its states of development; sometimes extended to include all intrinsic neoplasms of the brain and spinal cord, as astrocytomas, ependymomas, etc. (GBM and anaplastic an·a·plas·tic adj. 1. Relating to the surgical restoration of a lost or absent part. 2. Of, relating to, or characterized by cells that have become less differentiated. anaplastic 1. astrocytoma astrocytoma /as·tro·cy·to·ma/ (as?tro-si-to´mah) a tumor composed of astrocytes; the most common type of primary brain tumor and also found throughout the central nervous system, classified on the basis of histology or in order of ) and this disease is eventually fatal for most patients. Survival time for GBM patients ranges from six months for recurrent disease to 12 months with newly diagnosed disease despite aggressive treatments including surgery, radiation therapy and chemotherapy. GBM tumors mainly arise in the cerebral hemispheres (the main portions of the brain), but they can also occur in the brainstem, cerebellum cerebellum (sĕr'əbĕl`əm), portion of the brain that coordinates movements of voluntary (skeletal) muscles. It contains about half of the brain's neurons, but these particular nerve cells are so small that the cerebellum accounts for , or spinal cord spinal cord, the part of the nervous system occupying the hollow interior (vertebral canal) of the series of vertebrae that form the spinal column, technically known as the vertebral column. . Symptoms of a GBM can include headaches that are caused by increased intracranial pressure increased intracranial pressure Intracranial hypertension, see there , neurological deficits such as weakness, sensory loss, coordination difficulties, visual impairment Visual Impairment Definition Total blindness is the inability to tell light from dark, or the total inability to see. Visual impairment or low vision is a severe reduction in vision that cannot be corrected with standard glasses or contact lenses and , cognitive impairment affecting memory and language, seizures, and personality changes. About CINTREDEKIN BESUDOTOX CINTREDEKIN BESUDOTOX is a recombinant protein recombinant protein Molecular biology A protein encoded by recombinant DNA or generated from a recombinant gene. See Recombinant pharmacology. consisting of a single molecule composed of two parts: a tumor-targeting molecule (Interleukin-13 or IL13) and a cytotoxic agent (Pseudomonas Pseudomonas A genus of gram-negative, nonsporeforming, rod-shaped bacteria. Motile species possess polar flagella. They are strictly aerobic, but some members do respire anaerobically in the presence of nitrate. Exotoxin exotoxin /exo·tox·in/ (ek´so-tok?sin) a potent toxin formed and excreted by the bacterial cell, and free in the surrounding medium. , or PE38). IL13 receptors are present in appreciable numbers on malignant glioma cells, but only minimally, if at all, on healthy brain cells. The IL13 portion is designed to bind to to contract; as, to bind one's self to a wife s>. See also: Bind receptors on tumor cells like a key fits into a lock. The cancer cell appears to latch onto and absorb the IL13 and the attached PE38, causing destruction of the cancer cell. Healthy brain cells appear to be unharmed because they do not internalize internalize To send a customer order from a brokerage firm to the firm's own specialist or market maker. Internalizing an order allows a broker to share in the profit (spread between the bid and ask) of executing the order. the PE. The drug is delivered via Convection Enhanced Delivery (CED), a novel drug delivery system using catheters placed following tumor resection (removal), in areas with microscopic tumor spread or at risk of tumor spread around the tumor resection cavity. CINTREDEKIN BESUDOTOX has received Orphan Drug orphan drug, drug developed under the U.S. Orphan Drug Act (1983) to treat a disease that affects fewer than 200,000 people in the United States. The orphan drug law offers tax breaks and a seven-year monopoly on drug sales to induce companies to undertake the designation and Fast Track designation from the U.S. Food and Drug Administration (FDA FDA abbr. Food and Drug Administration FDA, n.pr See Food and Drug Administration. FDA, n.pr the abbreviation for the Food and Drug Administration. ). CINTREDEKIN BESUDOTOX was also accepted into FDA's Pilot 2 Program for continuous marketing applications. CINTREDEKIN BESUDOTOX has also received Orphan Drug designation in Europe. Promising data for this potential therapeutic advance in the treatment of GBM has been observed in Phase I/II trials, the results of which have been previously reported by the Company. In addition, the importance of adequate catheter positioning in order to achieve effective distribution of CINTREDEKIN BESUDOTOX in brain tissue was assessed in these Phase I/II trials, leading to specific guidelines for catheter positioning and deferred catheter placement used in the Company's ongoing Phase III PRECISE Trial. Improved catheter placement translated into a better patient outcome for the 45 (complete Phase I/II patient set) recurrent GBM patients treated post-tumor resection in the Phase I/II trials, with an overall median survival of 44.0 weeks (95% Confidence Interval confidence interval, n a statistical device used to determine the range within which an acceptable datum would fall. Confidence intervals are usually expressed in percentages, typically 95% or 99%. (CI): 36.1-55.6) including 40 percent of patients with less than 2 optimally positioned catheters, while patients with greater than or equal to 2 catheters optimally positioned surviving with a median of 55.6 weeks (95% CI: 36.1-74.3). Separately, one-year and two-year survival rates for recurrent GBM patients were approximately 52 percent and 18.5 percent respectively, for patients with greater than or equal to 2 catheters optimally positioned. Pivotal Phase III Trial - PRECISE PRECISE, an acronym for Phase III Randomized ran·dom·ize tr.v. ran·dom·ized, ran·dom·iz·ing, ran·dom·iz·es To make random in arrangement, especially in order to control the variables in an experiment. Evaluation of Convection Enhanced Delivery of IL13-PE38QQR with Survival Endpoint, www.precisetrial.com, is a randomized, controlled Phase III clinical trial Noun 1. phase III clinical trial - a large clinical trial of a treatment or drug that in phase I and phase II has been shown to be efficacious with tolerable side effects; after successful conclusion of these clinical trials it will receive formal approval from the . It was designed to enroll up to 300 patients in order to obtain 270 patients with confirmed GBM at first recurrence at study entry surgical resection for the intent-to-treat patient population, and compare overall survival, drug safety and quality of life of patients receiving CINTREDEKIN BESUDOTOX with patients receiving Gliadel Wafer in the treatment of first recurrent GBM following surgical tumor resection. PRECISE achieved the 270 patient intent-to-treat milestone (276 intent-to-treat) in early December after enrolling 294 patients. Patients were randomized so that 2 patients received CINTREDEKIN BESUDOTOX via CED for every 1 patient that received Gliadel Wafer placed in the resection cavity at the time of resection. The primary efficacy analysis of the trial will be based on the comparison of the overall patient survival curves of the two treatment groups. In June 2006, after conducing the trial's interim efficacy analysis after 160 patient deaths, the Data Monitoring Committee (DMC DMC Devil May Cry (video game) DMC Detroit Medical Center DMC Darryl McDaniels (rapper) DMC Destination Management Company DMC Del Mar College (Corpus Christi, TX) ) recommended that the PRECISE Trial continue as planned under the approved protocol. The DMC reported no treatment related adverse or serious adverse events that differed from previous reports and those normally associated with GBM and reported that compliance in terms of catheter placement guidelines was over 80%. The final efficacy analysis is currently expected to occur in the first quarter of 2007. NEOPHARM's Commitment to Oncology NEOPHARM employees share a common goal: bringing hope to cancer patients and their families through the research and development of new cancer drugs and therapies. The Company's oncology portfolio is built on two novel, proprietary platforms: a tumor-targeting platform, and the NeoLipid(R) Liposomal Drug Delivery platform. Through its research and clinical studies, as well as its work with physicians, scientists, and advocacy groups, NEOPHARM is helping to enhance the lives of cancer patients. About NEOPHARM, Inc. NEOPHARM, Inc., based in Waukegan, Illinois, is a publicly traded biopharmaceutical company dedicated to the research, development and commercialization of new and innovative cancer drugs for therapeutic applications. Additional information, including ongoing clinical trials, can be obtained by visiting NEOPHARM's Web site at www.NEOPHARM.com. Forward Looking Statements - This press release contains "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. The Company has tried to identify such forward-looking statements by use of such words as "expects," "intends," "hopes," "anticipates," "believes," "could," "may," "evidences" and "estimates," and other similar expressions, but these words are not the exclusive means of identifying such statements. Such statements include, but are not limited to, any statements relating to the Company's drug development program, including, but not limited to, clinical trials involving cintredekin besudotox, future patient survival in the Company's ongoing Phase I/II studies and the PRECISE trial for Cintredekin besudotox, the use of the CED procedure and any other statements that are not historical facts. Such statements involve risks and uncertainties, including, but not limited to, those risks and uncertainties relating to difficulties or delays in financing, development, testing, obtaining regulatory approval, the date when the final efficacy analysis in the PRECISE trial will be reported, production and marketing of cintredekin besudotox, unexpected side effects or inadequate therapeutic efficacy of Cintredekin besudotox that could slow or prevent Cintredekin besudotox from coming to market, uncertainty regarding the Company's ability to market its drug and non-drug products including, but not limited to, cintredekin besudotox, and other risks detailed from time to time in filings the Company makes with the Securities and Exchange Commission including its annual reports on Form 10-K and quarterly reports on Forms 10-Q. Such statements are based on management's current expectations, but actual results may differ materially due to various factors, including those risks and uncertainties mentioned or referred to in this press release. Accordingly, you should not rely on these forward-looking statements as a prediction of actual future results. |
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