NeoPharm and Collaborators Present IL13-PE38QQR Clinical Data in Brain Cancer
Additional and New Preliminary Data Unveiled at SNO 8th Annual Meeting Provide
Consistent Support for Further Development of This Novel Approach in Advance Of
Phase III Clinical Trial
LAKE FOREST, Ill., Nov. 17 /PRNewswire-FirstCall/ -- NeoPharm, Inc. today
announced that additional Phase I/II worldwide clinical trial data on
IL13-PE38QQR, the Company's novel tumor-targeting agent for malignant glioma,
from three clinical studies were presented at the 8th Annual Meeting of the
Society for Neuro-Oncology (SNO), held in Keystone, CO from November 13-16,
2003. Three abstracts (#RA-5, #TA-15 and #TA-39) were presented as poster
discussions and the fourth (#TA-30) was presented as a podium presentation. The
overall Phase I/II preliminary data from these three studies and a fourth drug
distribution study represent a combined experience from more than 75 patients in
various clinical settings, including intra- and peritumoral delivery of
IL13-PE38QQR for treatment of malignant glioma. The findings suggest consistent
evidence of tumor cytotoxic, cancer cell killing, effects of IL13-PE38QQR
against malignant glioma tumor cells and, although not designed to address
efficacy, encouraging survival results continue to be observed beyond two years. Copies of NeoPharm's IL13-PE38QQR abstracts have been published in
Neuro-Oncology, Volume 5, Issue 4, October 2003,
http://neuro-oncology.mc.duke.edu/. Copies of the actual posters presented,
with updated data, are available on the NeoPharm website
http://www.neophrm.com/.
"The findings across the Phase I/II studies appear to be most promising with
peritumoral infusion into brain tissue at risk for tumor recurrence and spread,"
commented James M. Hussey, NeoPharm's President and Chief Executive Officer.
"These data provide additional support to our commitment to advance IL13-PE38QQR
into a pivotal Phase III clinical trial for the treatment of patients with
malignant glioma. We are especially pleased by our advances with
convection-enhanced delivery (CED) and believe that CED will play an important
role in brain tumor therapy in the future." NeoPharm is preparing to initiate a pivotal Phase III clinical trial for
IL13-PE38QQR (the PRECISE trial) for the treatment of glioblastoma multiforme, a
deadly form of brain cancer. The Company currently anticipates that the drug
supply for PRECISE will be available by the middle of December 2003, and that
the clinical trial will begin in the fourth quarter of 2003 or the first quarter
of 2004. IL13-PE38QQR has received orphan drug designation in Europe and the
U.S., and fast track drug development program status from the U.S. Food and Drug
Administration (FDA). NeoPharm has exclusively licensed IL13-PE38QQR from the
National Cancer Institute and the FDA, and is developing the agent under a
Cooperative Research and Development Agreement (CRADA) in collaboration with the
laboratory of Raj K. Puri, MD, PhD, at FDA Center for Biologics Evaluation and
Research (CBER).
Phase I/II IL13-PE38QQR Preliminary Findings IL13-PE38QQR is currently under investigation in four ongoing Phase I/II
clinical trials in patients with recurrent malignant glioma. The first
IL13-PE38QQR clinical study is being conducted through the NCI Clinical Trial
Evaluation Program (CTEP)-funded New Approaches to Brain Tumor Therapy (NABTT)
Consortium. Johns Hopkins University Medical Center is the coordinating site
for NABTT. Results from 21 patients enrolled in this trial were presented as a
poster discussion at SNO (Abstract #TA-39). These patients were all diagnosed
with recurrent supratentorial malignant glioma. IL13-PE38QQR is administered by
CED, a novel technique using positive pressure infusion to distribute
therapeutic agents within brain tumors and in areas at risk for tumor spread.
Two infusions are planned eight weeks apart without planned tumor resection.
Patients are dosed with IL13-PE38QQR via two, intra-tumoral catheters at 200
microliters/catheter/hour for 96 hours (total 38.4 mL). The IL13-PE38QQR
concentration is being increased in individual cohorts to determine the maximum
tolerated dose (MTD). Six patients received IL-13PE38QQR at 0.125 micrograms/mL
followed by three patients at each dose level of 0.25, 0.50, 1.0, 2.0 and 4.0
micrograms/mL. Intratumoral infusion of the drug appears to be well tolerated
in this population, permitting dose escalation and patient accrual to proceed.
Similar adverse events occurred across all cohorts, with most being neurological
or related to neurosurgical site. Tumor response, either microscopic or
radiologic, has been observed in some patients. Although this trial was not
designed to determine efficacy, extended patient survival has also been
observed.
The second clinical study, presented in two poster discussion sessions
(Abstracts #RA-5 [radiographic findings] & #TA-15 [overall findings]), involves
several institutions including the University of California San Francisco
(UCSF), M.D. Andersen Cancer Center (MDACC), Memorial Sloan- Kettering Cancer
Center (MSKCC), and Yale University. Primary objectives of this study include,
determination of the dose of IL13-PE38QQR that produce tumor cell death,
referred to as the histologically effective concentration (HEC) and the
corresponding drug toxicities following IL13-PE38QQR infusion into the tumor and
areas adjacent to the tumor. Secondary objectives are the determination of time
to tumor progression and patient survival. A total of 29 patients have been
treated to date in this study. In Stage 1, patients receive drug intratumorally
before (escalating concentrations) and peritumorally after (0.25 micrograms/mL,
fixed) tumor resection. On Day 8 of Stage 1, en bloc tumor resection is
performed to assess HEC and 2-3 peritumoral catheters are placed adjacent to the
resection site in areas where residual tumor cells may be present. In Stage 2,
the pre-resection infusion is eliminated and post-resection drug concentrations
are escalated. In Stage 1, 15 patients were treated at escalating pre-resection
concentrations (0.25, 0.50, 1.0, and 2.0 micrograms/mL). Histopathological
(microscopic) analysis revealed early tumor necrosis in most patients receiving
concentrations of 0.5 micrograms/mL and higher. Five specimens had necrosis
topographically related to the catheter in an ovoid zone extending up to 2.5 cm. All patients were able to complete the post-resection infusion at 0.25
micrograms/mL.
With confirmation of the HEC in Stage I, the pre-resection infusion was omitted
and escalation of post-resection peritumoral infusion concentration began at 0.5
micrograms/ml in Stage 2. Stage 2 findings were presented earlier this year
during a plenary session of the American Association of Neurological Surgeons
(AANS) 71st Annual Scientific Meeting and as a poster presentation at the 15th
International Conference on Brain Tumor Research and Therapy. A total of nine
patients completed Stage 2 to determine the maximum tolerated infusion
concentration (MTIC). All patients tolerated the peritumoral infusion and no
dose limiting toxicities were observed for the six patients at 0.5
micrograms/mL. Two of three patients at 1.0 micrograms/mL developed symptomatic
radiographic changes near the former catheter insertion location. As a result,
0.5 micrograms/mL was designated the MTIC post- resection. Enrollment of
patients in Stage 3, to examine escalation of the infusion duration, has
completed. Stage 4, the final part of the study, to assess deferred catheter
placement post tumor resection is well underway. While this trial was not
designed to determine efficacy, clinical follow-up has revealed prolonged
overall patient survival from time of treatment to up to 125+ weeks (median 52
weeks). Furthermore, survival was more prolonged in patients with optimal
catheter placement and guidelines have been developed to insure consistent
catheter placement. "The data from this study are promising and offer the
potential for a therapeutic advance in the treatment of this dismal disease,"
commented Sandeep Kunwar, MD, Assistant Professor of Neurological Surgery and
Principal Investigator, Brain Tumor Research Center, at the University of
California, San Francisco.
The third clinical study presented as a podium presentation (Abstract #403) at
SNO described preliminary data from a clinical trial being conducted at six
participating sites including Tel Aviv Sourasky Medical Center and Chaim Sheba
Medical Center in Israel, University Hospital Eppendorf and University Hospital
Kiel in Germany, and the Cleveland Clinic and the University of Colorado in the
United States. This study is designed to determine the maximum tolerated dose
(MTD) in terms of infusion duration and drug concentration of IL13-PE38QQR
delivered by CED via one or two intratumoral catheters in patients with
recurrent or progressive malignant glioma prior to planned tumor resection.
Cohorts of 3-6 patients receive 0.50 micrograms/mL with escalating duration (4-7
days) to determine a MTD based on duration. After determination of maximum
duration, drug concentration is escalated from 1.0-4.0 micrograms/mL in cohorts
of 3-6 patients to determine a MTD based on concentration. Tumor necrosis at
6-13 days following infusion and proportion of patients surviving at 6 months is
also assessed. Twenty- two patients have been enrolled; comprising all four
duration periods and three out of four concentration levels. Duration of
infusion up to seven days and concentrations of 3.0 micrograms/mL appear to be
safe and well tolerated. Evidence of tumor necrosis in some patients has also
been observed. Although this trial was not designed to determine efficacy,
extended patient survival has also been observed.
A fourth clinical study being conducted at Duke University is assessing drug
distribution in patients undergoing treatment with IL13-PE38QQR. This study
utilizes a radioactive tracer to confirm drug distribution and parameters for
CED of drug.
For additional details regarding IL13-PE38QQR trial design, enrollment criteria
and participating centers please refer to http://www.clinicaltrials.gov/
(keyword: IL13-PE38QQR).
Background Information Malignant Glioma: The Disease
Malignant glioma, which includes glioblastoma multiforme and anaplastic
astrocytoma tumors, is diagnosed in approximately 17,500 people in the U.S. annually and claims approximately the same number of lives each year. As there
are very limited treatment options to prevent tumor progression, most people
with glioblastoma multiforme usually live for less than one year after initial
diagnosis, and less than six months after the first recurrence.
Mechanism of Action of IL13-PE38QQR Malignant glioma cells, as compared to normal brain cells, express
interleukin-13 (IL13) receptors at a high density. IL13 is an immune regulatory
cytokine, or protein, secreted by cells. IL13-PE38QQR (a recombinant protein) is
designed to detect and bind to IL13 receptors on the surface of malignant glioma
cancer cells, and then selectively deliver a potent bacterial cytotoxic agent
called PE38, derived from a bacteria called Pseudomonas aeruginosa, to destroy
tumor cells while sparing healthy surrounding cells. In contrast, conventional,
non-specific chemotherapeutic drugs attack abnormal cancer cells by stopping
them from dividing and reproducing, but can also damage normal cells because
these agents do not discriminate between cancerous and healthy cells. Furthermore, standard chemotherapy drugs are usually administered systemically,
which leads to their distribution throughout the body rather than to one area,
such as a tumor in the brain. Common chemotherapy side effects may occur when
bone marrow is damaged and cannot produce enough red blood cells (causing
weakness and fatigue), white blood cells (lowering the body's resistance to
infections) or platelets (preventing blood from clotting properly, which can
lead to excessive bleeding).
IL13-PE38QQR, on the other hand, is being developed as a highly specific
tumor-targeting agent. It is administered directly to the tumor by positive-
pressure CED, through catheters inserted in the tumor or brain surrounding the
tumor, before and/or following surgical resection of the tumor. CED is designed
to infuse IL13-PE38QQR directly to the tumor site and adjacent brain tissue to
prevent recurrence of tumor cell growth. Investigators have sought to identify
the optimum "therapeutic window" to provide patients with the safest, most
effective dose at sufficient concentration to kill malignant cells while
minimizing exposure to healthy brain tissue.
A study describing tumor regression mechanisms by IL-13 receptor-targeted cancer
therapy involving apoptotic pathways was published in the 1 January 2003 issue
of the International Journal of Cancer, a Publication of the International Union
Against Cancer. The authors provide evidence that human glioma tumor cells that
express the IL-13 receptor undergo programmed cell death, or apoptosis,
following intratumoral administration of IL13-PE38QQR, by two major pathways.
About NeoPharm NeoPharm, Inc., based in Lake Forest, IL, is a publicly traded biopharmaceutical
company dedicated to the research, development and commercialization of new and
innovative cancer drugs for therapeutic applications. The Company has a broad
portfolio of compounds in various stages of development.
Additional information about NeoPharm and recent news releases can be obtained
by visiting NeoPharm's Website at: http://www.neophrm.com/ . For copies of
scientific abstracts related to IL13-PE38QQR from recent medical meetings,
contact Ken Johnson, PharmD, NeoPharm, at 847.295.8678.
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 the initiation, progress and outcomes of clinical trials involving
IL13-PE38QQR, 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 development,
testing, regulatory approval, production and marketing of the Company's drug and
non-drug compounds, including, but not limited to IL13-PE38QQR, uncertainty
regarding the availability of third party lyophilization capacity, uncertainty
regarding the outcome of damage claims made by or against the Company, including
the outcome of the pending arbitration with Pharmacia, unexpected adverse side
effects or inadequate therapeutic efficacy of the Company's drug and non-drug
compounds that could slow or prevent products coming to market, uncertainty
regarding the Company's ability to market its drug and non-drug products
directly or through independent distributors, the uncertainty of patent
protection for the Company's intellectual property or trade secrets and other
risks detailed from time to time in filings the Company makes with the
Securities and Exchange Commission including our annual reports on Form 10-K and
our 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. DATASOURCE: NeoPharm, Inc.
CONTACT: Larry Kenyon, CFO of NeoPharm, Inc., +1-847-295-8678, Investors contact, Janet Dally of MontRidge, LLC, +1-203-894-8038, or Media contact, Kristin Fayer of Outlook Marketing, +1-847-509-3099 Web site: http://www.neophrm.com/
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