Healthcare Industry News:  Brainlab 

Biopharmaceuticals Oncology Neurosurgery

 News Release - April 26, 2006

Optimizing Catheter Positioning Improves Drug Distribution of Cintredekin Besudotox via Convection Enhanced Delivery

Optimal Catheter Positioning Improves Survival Benefit

WAUKEGAN, Ill.--(HSMN NewsFeed)--April 26, 2006--NeoPharm, Inc. (Nasdaq:NEOL ) today announced that the use of a novel software-based catheter planning and positioning system developed by Brainlab AG may optimize the efficacy and safety of tumor targeting therapies delivered via Convection Enhanced Delivery (CED), specifically cintredekin besudotox (IL13-PE38QQRR), an investigational treatment being studied for the treatment of patients with first recurrent glioblastoma multiforme.

In a study presented via poster presentation today by John Sampson, MD, Associate Professor of Neurosurgery and Assistant Professor of Pathology at Duke University Medical Center, investigators evaluated and assessed the clinical usefulness of a novel simulation algorithm using magnetic resonance diffusion tensor imaging (MR DTI) to predict the distribution of a drug administered via CED. Overall, investigators found that the new software simulation technique provides valuable patient-specific information including volume, location, and geometry of potential drug distribution. This information can be effectively used to assist in optimizing planning and subsequent positioning of drug delivery catheters for CED. The new technology is applied to neoplastic and other CNS pathologies. It is hoped that routine use of such algorithms in the pre-operative planning of catheter placement will improve the safety and efficacy of drugs delivered by CED, specifically cintredekin besudotox (IL13-PE38QQR).

"These data are promising because in the past it has been difficult to effectively treat the infiltrative nature of this type of tumor," said Dr. Sampson. "Using the methods from this study, neurosurgeons will be able to pre-operatively simulate where drugs, such as cintredekin besudotox, are distributed in the brain allowing for greater catheter placement optimization, which may yield improved survival benefits for patients."

Study Background and Results

This study was conducted within the context of a pilot study with intracerebral CED of the tumor targeted cytotoxin, cintredekin besudotox (IL13-PE38QQR), co-infused with 123I-labeled human serum albumin (123I-HSA) as surrogate for drug distribution, in patients with recurrent malignant glioma. SPECT scans provided quantitative information on the spatial distribution of the 123I-HSA which could then be compared to the software simulation result. Usefulness of the software algorithm was assessed based on its ability to eliminate sub-optimally positioned catheters that would likely limit drug distribution due to leakage into cerebrospinal fluid (CSF) spaces, and on the match of the volume of distribution of the infusate as shown by SPECT and simulation.

Of the catheters evaluated (n=14):
  • The algorithm had a high sensitivity and specificity for identifying catheter trajectories that leaked infusate into the subarachnoid or ventricular cerebrospinal fluid spaces, giving an overall specificity of 100% (95% CI, 59% - 100%) and a sensitivity of 71% (95% CI, 29% - 96%) (p=0.021).
  • For the catheters that produced drug distribution in the desired anatomic region (7/14), as evidenced by SPECT, the overall volume of distribution match was 66%.
Overall clinical utility was based on an assessment scheme that combined the sulcus detection algorithm with the simulation algorithm. In 84.6% of the evaluated infusions clinical utility of the software was concluded, helping surgeons to easily identify invalid catheter trajectories, and further supporting them in targeting the treatment to the brain regions that are estimated to affect patient survival.

This data further supports catheter positioning guidelines developed for the cintredekin besudotox Phase III PRECISE trial. With the guidelines being part of surgical planning software that takes the patient-specific anatomy into account, the software tool, which is compatible with a variety of neurosurgical navigation equipment, will help to ensure these guidelines are followed in day-to-day practice.

According to a spokesperson for Brainlab, iPlan Flow, Brainlab's FDA approved simulation and planning software for CED that incorporates results from this study, represents a complete solution including hospital support services. The software package offers significant improvement on the success of CED in day-to-day clinical practice. The solution that is now available is extremely scalable so that for each individual patient, the physician gains the ability to deliver the best possible treatment.

About Convection Enhanced Delivery

Convection enhanced delivery (CED) involves the placement of one or more catheters into a brain tumor or nearby brain tissue used to infuse slowly and continuously an anti-tumor drug or other substance over several days. This technique allows relatively large volumes of brain tissue to be treated. CED is used to infuse cintredekin besudotox directly to brain tissue at risk for residual infiltrating tumor in order to prevent or delay tumor recurrence (tumor cell growth).

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 less than 2 adequately positioned catheters, while patients with greater than or equal to 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, 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 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 (greater than or equal to 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.

About Brainlab

Brainlab, a privately held company headquartered in Munich, Germany, was founded in 1989 and is specialized in the development, manufacture, and marketing of medical technology for neurosurgery, radiosurgery / radiotherapy, orthopedics, and ENT. Among the products developed by Brainlab are software and hardware components for image-guided surgery and radiotherapy as well as integrated systems for stereotactic radiosurgery. With around 2,280 systems installed in over 65 countries, Brainlab is among the market leaders in image-guided medical technology. Brainlab today employs 740 people worldwide and has 15 offices across Europe, Asia, North and South America and Australia.

For more information, visit Brainlab at www.Brainlab.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 including cintredekin besudotox, future patient survival in the Company's ongoing Phase I/II studies and PRECISE trial, 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.


Source: NeoPharm

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