FeRx Presents Clinical and Preclinical Data from Studies Using MTCs to Treat Tumors
Phase I/II Clinical Study of MTC-DOX Shows Possible Activity Against HCC
While Preclinical Studies of MTC-90Y Suggest Feasibility of Intra-Tumoral
Radiotherapy Using Magnetic Targeting
FeRx Inc., a targeted drug delivery company, today presented results at the 28th Annual Scientific Meeting of the Society of Interventional Radiology, Salt Lake City, from clinical and preclinical studies using the company's proprietary Magnetic Targeted Carrier (MTC) drug delivery platform.
In the clinical study report, Mark W. Wilson, M.D., Assistant Professor of Radiology, Department of Radiology, UCSF Medical Center, presented results of a multi-center, Phase I/II trial of hepatic intra-arterial delivery of doxorubicin hydrochloride adsorbed to magnetic targeted carriers (MTC-DOX) in patients with hepatocellular carcinoma (HCC). In the preclinical study report, Jeff Geschwind, M.D., Associate Professor of Radiology, Oncology, and Surgery at The Johns Hopkins University School of Medicine, and Director of Interventional Radiology at The Johns Hopkins Hospital, presented results of studies investigating the use of MTCs in the local delivery of the radionuclide 90Y to the livers of rabbits implanted with VX2 tumors.
"We are encouraged by the results of these two studies, and have already initiated a global Phase II/III randomized study in HCC following from the report presented by Dr. Wilson," said Jacqueline Johnson, Ph.D., President and CEO of FeRx. "The preclinical work reported on by Dr. Geschwind demonstrates the versatility and capability of the MTC platform in delivering a variety of pharmaceutical agents, in this case supporting the feasibility of intra-tumoral radiotherapy using magnetic targeting."
The study reported on in Dr. Wilson's oral presentation was entitled "A Phase I/II Trial of Hepatic Delivery of Doxorubicin Adsorbed to Magnetic Targeted Carriers in Patients with HCC" and was designed to test the safety, maximum tolerated dose, pharmacokinetic profile, and tumor response following selective arterial infusion of MTC-DOX under magnetic guidance in patients with HCC. A Phase I/II dose escalation study was undertaken in 33 patients in which MTC-DOX was delivered to the tumor via selective hepatic arterial catheterization. An external magnet was positioned over the tumor to guide the MTC-DOX into the proper location and to extravasate the material into the tumor parenchyma. Tumor localization was confirmed by MRI post administration. A range of tumor sizes from 3 to 222 cm2 was treated.
Tumor localization of MTC-DOX was achieved in 31 of 33 patients in the study. Even with high doses of doxorubicin in the MTC-DOX patients, measurements of doxorubicin in plasma were undetectable or low. Since high plasma levels correspond to severe side effects, the low levels seen with MTC-DOX indicate the possibility that the MTC technology can be used to reduce or eliminate the toxic side effects associated with chemotherapeutic agents. Median survival for all patients as of 24 August 2002 was 7.5 months, and survival for patients treated above a minimally effective dose of 0.37 mg of doxorubicin/cm2 of tumor area was 11.5 months. Drawing conclusions from the clinical trial, Dr. Wilson suggested that the study indicates that intra-arterial administration of MTC-DOX has no clinically significant toxicities and demonstrates possible activity against HCC. The lesion control rate in the study was 83% and median survival exceeded that reported for historical controls.
The presentation was co-authored by Robert K. Kerlan Jr., M.D., Professor of Clinical Radiology University of California, San Francisco and Chief of Interventional Radiology UCSF Mount Zion Medical School; Eric Walser, M.D., Associate Professor of Radiology and Director of Vascular and Interventional Radiology, University of Texas Medical Branch; Joy Koda, Ph.D., Vice President, Clinical Development, FeRx Inc.; Alan Venook, M.D., Professor of Clinical Medicine, University of California, San Francisco and Chief of the Gastrointestinal Oncology Clinic, UCSF Comprehensive Cancer Center; and, Scott C. Goodwin, M.D., Chief of Imaging, Department of Veterans Affairs, Veterans Administration Hospital, Los Angeles and Professor of Radiology,UCLA Medical Center.
The preclinical study reported on in the oral presentation by Dr. Geschwind, entitled "Magnetic Targeted Delivery of 90Y to VX2 Rabbit Liver Tumors," was designed to investigate magnetic targeted delivery of the radionuclide 90Y to rabbit liver tumors. In the study, VX2 liver tumors that had been implanted in rabbit livers were treated with 90Y-labeled Magnetic Targeted Carriers (MTC-90Y) or MTCs alone. Upon selective catheterization of the left hepatic artery leading to the tumor, a single infusion of one of three doses intended to deliver 50, 100 or 150 Gy of 90Y was administered. An external magnetic field was focused on the tumor throughout the infusion and for 15 minutes following treatment. Radioactivity was measured in blood collected after dosing and biodistribution of 90Y in the liver, lung, spleen, and bone was evaluated over time by liquid scintillation counting. The remaining animals were recovered and observed for 7 days.
No embolization or adverse clinical signs were associated with this procedure. Blood levels of radioactivity were less than or equal to 1% of 90Y administered and decreased between 30 minutes and 1 hour. Radioactivity measured in organs on various days post-dosing showed that the majority of the 90Y was localized in the liver. MRI performed 7 days after treatment showed the presence of MTCs in the tumors and microscopic examination of tissue showed that these particles were confined to the liver. Importantly, liver necrosis was greater in treated animals (greater than or equal to 70% necrosis) when compared to controls (50% necrosis), with complete tumor destruction seen at the highest dose administered. The study suggests the feasibility of intra-tumoral radiotherapy using magnetic targeting and provides the foundation for additional investigations.
The study was co-authored with Hicham Kobeiter, M.D., Research Fellow, The Johns Hopkins University School of Medicine; Caryn Peterson, Vice President of Regulatory Affairs and Quality Assurance, FeRx Inc.; and, Tina Leakakos, Ph.D., Associate Director, Preclinical Development, FeRx Inc.
FeRx Inc. is a privately held, product-oriented, targeted drug delivery company dedicated to the development and commercialization of its proprietary Magnetic Targeted Carrier (MTC) technology to improve patient care, reduce toxicity and increase efficacy of known drugs for the treatment of cancer. MTCs are microparticles composed of metallic iron and activated carbon that serve as delivery vehicles for the site specific targeting, retention, and release of a variety of pharmaceutical agents, including small molecules, biologics and genetic vectors.
The MTC technology uses a small, externally positioned magnet to create a localized magnetic field within the body. MTCs enable pharmaceutical agents to be magnetically targeted to specific sites in the body. The physical force created by the magnetic field draws the MTC-drug compound into the targeted disease area. This process results in localization and retention of the delivered pharmaceutical agents at the desired site following removal of the magnetic field.
Current clinical studies of MTCs being conducted by FeRx are designed to demonstrate the intra-arterial delivery of magnetically targeted pharmaceuticals to specific areas of the body while reducing systemic toxicity and increasing the local concentration of drug at the target site. These trials are focused on the delivery of FeRx's lead product, MTC-DOX (doxorubicin), to primary liver tumors (hepatocellular carcinoma -- HCC) and to tumors that have metastasized to the liver.
For more information about FeRx, Inc., please visit the web site.
4/11/2003
|
|
