Healthcare Industry News: Cintredekin Besudotox
News Release - September 18, 2006
NEOPHARM Presents Updated CINTREDEKIN BESUDOTOX Phase I/II Median Survival Data at European Association of Neuro-Oncology (EANO) Meeting
Deferred Catheter Positioning Provides a Statistically Significant Improvement in Achieving Optimal Catheter PlacementWAUKEGAN, Ill.--(HSMN NewsFeed)--Sept. 18, 2006--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 (GBM). 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 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), 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 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 related to prolonged survival. Furthermore, post-operative stereotactic 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 in adults. According to the Central Brain Tumor Registry of the United States (CBTRUS, 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 (GBM and anaplastic astrocytoma) 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, or spinal cord. Symptoms of a GBM can include headaches that are caused by increased intracranial pressure, neurological deficits such as weakness, sensory loss, coordination difficulties, visual impairment, cognitive impairment affecting memory and language, seizures, and personality changes.
About CINTREDEKIN BESUDOTOX
CINTREDEKIN BESUDOTOX is a recombinant protein consisting of a single molecule composed of two parts: a tumor-targeting molecule (Interleukin-13 or IL13) and a cytotoxic agent (Pseudomonas Exotoxin, 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 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 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 designation and Fast Track designation from the U.S. Food and Drug Administration (FDA). 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 (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 Evaluation of Convection Enhanced Delivery of IL13-PE38QQR with Survival Endpoint, www.precisetrial.com, is a randomized, controlled Phase III clinical trial. 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) 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® 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.
Source: NEOPHARM
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