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Ø Phase I Study Confirms Combination Therapy that Includes Cintredekin Besudotox May Be An Option For This Patient Population
SAN FRANCISCO, California - April 25, 2006 - NeoPharm, Inc. (Nasdaq: NEOL) today announced that, based upon a recent Phase I study, evidence was provided that cintredekin besudotox (IL13-PE38QQR) appears to be safe and well tolerated in newly diagnosed malignant glioma patients. Results from the Phase I study will be presented at the 74th Annual Meeting of the American Association of Neurological Surgeons (AANS) held in San Francisco on Tuesday, April 25, 2006
"We always try to optimize the safety and efficacy of currently available therapies when used in combination with investigational therapies," commented Michael Vogelbaum, M.D., Ph.D., Vice-Chairman and Associate Director of Neurosurgical Oncology, Brain Tumor Institute, Cleveland Clinic Foundation. "We are encouraged that cintredekin besudotox can apparently be safely used in combination with two currently available therapies, radiation therapy and temozolomide, and that the combination may provide benefits for this patient population."
Patients in the Phase I study underwent a gross total resection of tumor followed by the placement of 2-4 stereotactically placed intraparenchymal catheters, and administration of cintredekin besudotox (0.25µg/mL or 0.5µg/mL) infused over 96 hours. This was followed, 10-14 days later, by standard fractionated radiation therapy (5940-6100 cGy [centi-Gray units], 5 days/week for 6-7 weeks) with or without temozolomide (75 mg/m2/day, 7 days/week during radiation). Safety was assessed over an 11-week observation period following catheter placement.
Nineteen patients were enrolled and received cintredekin besudotox. Seventeen of 19 patients (12 male and 7 female, median age 55, all had GBM) have completed treatment including cintredekin besudotox, radiation therapy ± temozolomide. No patients experienced dose limiting toxicities in the first two cohorts (0.25 µg/mL cintredekin besudotox + radiation [n=3] and 0.25 µg/mL cintredekin besudotox + radiation + temozolomide [n=3]). After one dose-limiting toxicity (DLT) (seizure), the third cohort (0.5 mg/mL cintredekin besudotox + radiation) was expanded to 6 patients without any DLT. Three patients treated at 0.5 µg/mL + radiation + temozolomide have completed the safety observation without any DLT. Two additional patients are currently being treated and another one was recently enrolled to confirm the safety of 0.5 µg/mL + radiation + temozolomide.
Adverse events considered related to cintredekin besudotox or catheter placement were consistent with adverse events observed in Phase I studies of cintredekin besudotox administered as monotherapy in patients with recurrent malignant glioma.
Patients continue to be followed for survival.
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 (www.cbtrus.org), GBM tumors account for approximately 22 percent of all adult primary brain tumors and usually affect men more commonly than women, particularly men between the ages of 60 and 85 years. GBM is rare in children, comprising approximately three percent of all childhood tumors. According to the CBTRUS, approximately 18,500 people are diagnosed annually with primary malignant brain tumors and approximately 13,000 people die from this disease annually. Survival time for 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 brain stem, cerebellum, or spinal cord. Symptoms of a GBM can include headaches that are caused by increased intracranial pressure, memory loss, seizures, personality changes, and coordination difficulties.
About Cintredekin Besudotox (IL13-PE38QQR)
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 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. IL13 receptors are present in appreciable numbers on malignant glioma cells, but only to a minimal amount 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 PE, causing destruction of the cancer cell. Healthy brain cells appear to be unharmed because they do not internalize the PE.
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. In addition, the importance of adequate catheter positioning in order to achieve optimal distribution of cintredekin besudotox in brain tissue was assessed, leading to the 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 42 percent of patients with <2 adequately positioned catheters, while patients with ?2 catheters adequately positioned surviving with a median of 53.6 weeks (95% CI: 36.1-70.3). Separately, one-year and two-year survival rates for recurrent GBM patients were 40 percent and 13 percent respectively.
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
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 December 2005, an independent Data Monitoring Committee (DMC) recommended that the PRECISE Trial continue as planned under the approved protocol. The DMC observed no treatment related adverse or serious adverse events that differed from those seen in the Phase I/II trials, and observed that, at that time, optimal catheter placement (?2 catheters adequately positioned) had been achieved in more than 80% of patients. A planned interim efficacy analysis (triggered at 160 deaths) is expected to occur in late-second or early third quarter of 2006, and a final efficacy analysis (triggered at 215 deaths) is currently expected to occur late in the fourth quarter of 2006 or 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 PRECISE trial for cintredekin besudotox, 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, production and marketing of the Company's drug and non-drug compounds, including, but not limited to, cintredekin besudotox, uncertainty regarding the availability of third party production capacity, unexpected adverse side effects or inadequate therapeutic efficacy of the Company's drug and non-drug compounds, including, but not limited to, cintredekin besudotox, that could slow or prevent products coming to market, uncertainty regarding the Company's ability to market its drug and non-drug products, including, but not limited to, cintredekin besudotox, directly or through independent distributors, the uncertainty of patent protection for the Company's intellectual property or trade secrets, 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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