Inovio: final melanoma trial results confirm systemic effect and safety

First-Ever Human Trial of DNA-Based Immunotherapy Delivered Using Inovio Biomedical’s Electroporation Technology Shows Safety  and Durable Systemic Clinical Response
 
Plasmid IL-12 and Electroporation Combination Against
Metastatic Melanoma Achieves Systemic Response in Untreated Lesions Without Reaching Dose-Limiting Toxicity
 
Pioneering Results Published in Journal of Clinical Oncology
 
SAN DIEGO, Dec. 2, 2008 -- Inovio Biomedical Corporation (AMEX:INO), a leader in enabling the development of DNA vaccines using electroporation-based DNA delivery, announced today the final results of a Phase I clinical study demonstrating safe and effective treatment of metastatic melanoma in the first-in-man trial of a DNA-based therapy designed to express a therapeutic protein through in vivo delivery using electroporation. The data was presented in the peer-reviewed Journal of Clinical Oncology in a paper prepared by Drs. Adil Daud, Richard Heller et al, titled, “Phase I Trial of Interleukin-12 Plasmid Electroporation in Patients With Metastatic Melanoma.”
 
The paper presented results of a Phase I clinical study sponsored by the Moffitt Cancer Center in Tampa, Florida. The study was designed to assess the use of electrical pulses generated by Inovio's proprietary electroporation technology to deliver into tumor cells a plasmid DNA encoding a cytokine, interleukin-12, which stimulates adaptive and innate immunity. The paper concluded: “This first human trial, to our knowledge, of gene transfer utilizing in vivo DNA electroporation in metastatic melanoma showed that it is safe, effective, reproducible, and titratable.” The findings showed not only regression of treated melanoma skin lesions, but also regression of distant untreated lesions, suggesting a systemic immune response to the localized treatment.
 
Dr. Adil Daud, principal investigator of the study at the Moffitt Cancer Center and now Associate Professor, Director, Melanoma Clinical Research,UCSF Medical Center, stated: “The fact that more than half of the patients showed stabilization or regression of their melanoma lesions is encouraging. What is particularly compelling is the regression of untreated tumors, with 10% of patients treated with IL-12 and electroporation showing complete tumor regression of both treated and untreated tumors. These results have opened a door to greater hope for finding a better treatment for cancers such as melanoma.”
 
Richard Heller, PhD, Executive Director,Frank Reidy Research Center for Bioelectrics, Old Dominion University, a former University of South Florida professor of Molecular Medicine and Dr. Daud's co-researcher on the study, stated: “In prior studies of DNA-based immunotherapies, direct injection of DNA into tissue suffered from a low rate of gene transfer. Other delivery methods, particularly viral vectors, have safety considerations. Now, for the first time in human trials, our study demonstrates in vivo electroporation’s vital role in facilitating gene transfer in a safe and reproducible manner. These results suggest that electroporation-mediated plasmid delivery is a powerful new tool for effective gene transfer with implications for the clinical arena.”
 
Avtar Dhillon, MD, Inovio's president and CEO, stated:“The life-saving potential of DNA-based immunotherapies and vaccines for cancer has always been tempered by the lack of a safe and efficient delivery method. These results represent an important advance in stepping over that barrier. With Inovio’s electroporation technology we’ve significantly enhanced gene transfer efficiency while retaining the widely recognized safety of plasmid DNA.”
 
Highlights of the study results, as reported in the paper, include:
 
-     In this Phase I study, eligible patients had stages IIIB/C or IV metastatic melanoma with at least two subcutaneous or cutaneous lesions accessible for electroporation.
-     Twenty-four patients were enrolled in seven cohorts with escalating dose levels of plasmid IL-12 between December 2004 and February 2007. Locally injected plasmid IL-12 was followed by electroporation.
-     The experimental regimen was found to be safe and well tolerated, with minimal systemic toxicity. Because there was no dose-limiting toxicity in cohorts one through five, the experimental plan was amended to add two additional cohorts. Transient pain with the administration of the electrical pulses was the most frequent adverse event experienced by patients.
-     The study demonstrated significant and dose-dependent increases in intratumoral IL-12 protein expression and concomitant increases in intratumoral levels of IFN-γ.
-     Sixty lesions (76%) were observed to have greater than 20% necrosis (death of tumor cells), with 19 (24%) having 50% - 99% necrosis, and 25 (32%) having 100% necrosis.
-     Ten subjects (53%) showed evidence of a systemic response (either stable disease or a complete response) during the study.
-     Injected lesions and distant non-injected lesions showed regression after treatment. Of 19 patients with additional sites of disease outside of the treated lesions, two (10%) with untreated distant lesions and no other systemic therapy showing complete regression of all metastases. These responses occurred over 6 – 18 months, with gradual volume loss occurring at sites distinct from the electroporated sites, arguing for immune system involvement. Neither of these patients has developed any new evidence of distant disease to date. Six of 19 (32%) showed disease stabilization lasting from 4 – 20 months.
-     Electroporated tumors demonstrated CD4+ and CD8+ lymphocytic infiltrate in the treated lesions.
 
Other observations stated, with related references, in the paper include:
 
-     In other studies, the “delivery of IL-12 in the form of recombinant protein caused significant toxicity. This toxicity was reduced or eliminated in this study by delivering the gene encoding IL-12.”
-     “Local intratumoral injection of IL-12 plasmid [without electroporation] in a recent unrelated phase I study using the same plasmid as our electroporation study resulted in local tumor regression in five of 12 patients, but no change was seen in untreated distant lesions.”
-     “When compared with other techniques of gene delivery, electroporation seems to produce a greater magnitude of clinical benefit in this aggressive and often fatal disease [metastatic melanoma].”
 
 
Dr. Richard Heller, Old Dominion University, will be presenting at DNA Vaccines Forum 2008, which takes place December 9 - 11 in Las Vegas, NV. Other representatives of Inovio Biomedical, partners such as Tripep AS, and VGX Pharmaceuticals (with which Inovio has signed a definitive merger agreement), will also be making presentations regarding electroporation-delivered DNA vaccines.
 
About Inovio Biomedical Corporation
 
Inovio Biomedical is focused on developing DNA vaccines for cancers and infectious diseases using its novel method for DNA delivery – electroporation – which uses brief, controlled electrical pulses to increase cellular uptake of useful biopharmaceuticals. Initial human data has shown that Inovio’s electroporation-based DNA delivery technology can significantly increase gene expression and immune responses from DNA vaccines. Immunotherapy partners include Merck, Wyeth, Vical, University of Southampton, Moffitt Cancer Center, the U.S. Army, National Cancer Institute, and International Aids Vaccine Initiative. Inovio’s technology is protected by an extensive patent portfolio covering in vivo electroporation. The company has entered into a definitive merger agreement with VGX Pharmaceuticals. More information is available at www.inovio.com
 
CONTACTS:                                                                                                                            
Investors:     Bernie Hertel, Inovio Biomedical, 858-410-3101
Media:         Ron Trahan, Ronald Trahan Associates Inc.508-359-4005x108      

Posted: December 2008

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