Inovio Pharmaceuticals Completes PENNVAX™-B HIV Vaccine Phase I Study, Demonstrates Best-in-Class T-Cell Immune Responses
Significant T-cell responses demonstrate potential of HIV synthetic immunogen delivered using electroporation
Sep 14, 2011
BLUE BELL, Pa., Sept. 14, 2011 /PRNewswire/ -- Inovio Pharmaceuticals, Inc. (NYSE Amex: INO), a leader in the development of synthetic immunogens against cancers and infectious diseases, announced today that it has achieved best-in-class immune responses in a Phase I clinical study of PENNVAX™-B, its product for the prevention of the HIV sub-type prevalent in the US and Europe. These end of study results were presented at the AIDS Vaccine Conference in Bangkok, Thailand.
Dr. Spyros Kalams, Associate Professor of Medicine Vanderbilt University Medical Center and principal investigator of Vanderbilt's HIV Vaccine Trials Unit and of this clinical study, said, "These data show for the first time that HIV-specific immune responses may be enhanced with DNA and a plasmid cytokine adjuvant (IL-12) delivered via electroporation. The results of this study represent a significant advance for the ability of a DNA based vaccine to generate high levels of immune responses against HIV antigens and is transformative for DNA vaccination."
The HVTN-080 Phase I study enrolled 48 healthy, HIV-negative volunteers to assess safety and levels of immune responses generated by Inovio's PENNVAX™-B vaccine delivered with its CELLECTRA® electroporation device. PENNVAX™-B consists of SynCon® immunogens targeting HIV gag, pol, and env proteins from HIV subtype B commonly found in North America and Europe. This randomized, double-blind, multi-center study was sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), an agency of the National Institutes of Health, and conducted by the NIAID-funded HIV Vaccine Trials Network (HVTN) at several clinical sites.
Of the 48 total volunteers, eight subjects received a placebo, 10 subjects received a 3 mg dose (1 mg dose of each of three DNA plasmids – gag, pol, env) of Inovio's SynCon® PENNVAX™-B vaccine, and 30 subjects received a 3 mg dose of PENNVAX™-B along with 1 mg of GENEVAX™IL-12 DNA. All volunteers received vaccine or placebo administered via intramuscular injection with electroporation at months 0, 1, and 3. The T-cell immune responses were detected using a validated flow cytometry-based intracellular cytokine staining (ICS) assay at the HVTN core immunology laboratory at the Fred Hutchinson Cancer Research Center (Seattle, WA).
These data indicate that antigen-specific T-cell responses were generated by the vaccine in a majority of subjects. Overall, either CD4+ or CD8+ or both T-cell responses were observed against at least one of the vaccine antigens in 83.3% (30 of 36) of evaluated subjects after three vaccinations using electroporation. The response rate increased to 88.9% (24 of 27) of evaluated subjects after three vaccinations with electroporation plus the IL-12 cytokine gene adjuvant. The investigators in this study concluded that PENNVAX™-B + IL-12 plasmid delivered via electroporation led to frequencies and magnitudes of cellular immune responses equal to or greater than those reported from current vector-based HIV vaccines such as adenovirus or traditional DNA vaccination without electroporation. Further trials delivering an HIV DNA vaccine using electroporation with or without IL-12 as a vaccine strategy are merited.
Specifically, after three vaccinations with the PENNVAX™-B vaccine given with IL-12 and electroporation:
- Antigen-specific CD4+ T-cell responses were generated by the vaccine in 80.8% of evaluated vaccine recipients (21 of 26).
- Significantly strong antigen-specific, CD8+ T-cell responses were also generated by the vaccine in 51.9% of evaluated vaccine recipients (14 of 27).
- In an assessment of immune response durability out to six months post dose 3, 53.6% (15 of 28) of the subjects maintained positive CD4+ T-cell responses and 42.9% (12 of 28) of the subjects maintained positive CD8+ T-cell responses out to six months.
- Compared to the previously conducted HVTN 070 Phase I study, which assessed PENNVAX™-B with cytokine adjuvant IL-12 at double the dose, with four vaccinations, but without electroporation delivery, response rates in HVTN 080 with electroporation were significantly higher for both CD4+ responses (40.7%) and CD8+ T cell responses (3.6%).
- Samples from eight placebo recipients and pre-vaccine samples from vaccine recipients were also tested and were negative for both CD4+ T-cell responses and CD8+ T-cell responses.
- PENNVAX™-B delivered using the CELLECTRA® intramuscular electroporation delivery device with or without IL-12 was safe and generally well tolerated. There were no vaccine-related serious adverse events. Reported adverse events and injection site reactions were mild to moderate and required no treatment.
Dr. J. Joseph Kim, Inovio's President and CEO, said: "We are excited by the final results of the HVTN-080 study. These data are consistent with the previously announced interim results and unequivocally demonstrate the impact electroporation has on improving the immune potency of DNA vaccination. We appreciate the close collaboration with the NIH DAIDS and HVTN groups to systematically evaluate the immunogenicity of DNA immunogens together with cytokine adjuvants and delivery systems. We look forward to a continuing fruitful partnership with the HVTN and the DAIDS/NIH to further develop our HIV vaccine products to the next level."
About the HVTN
The HIV Vaccine Trials Network (HVTN), headquartered at Fred Hutchinson Cancer Research Center in Seattle, Wash., is an international collaboration of scientists and educators searching for an effective and safe HIV vaccine. The HVTN's mission is to facilitate the process of testing preventive vaccines against HIV/AIDS. The HVTN conducts all phases of clinical trials, from evaluating experimental vaccines for safety and the ability to stimulate immune responses, to testing vaccine efficacy. Support for the HVTN comes from the National Institute of Allergy and Infectious Diseases (NIAID) of the U.S. National Institutes of Health (NIH). The Network's HIV Vaccine Trial Units are located at leading research institutions in 27 cities on four continents. Internationally renowned HIV vaccine and prevention researchers lead the units.
About Inovio Pharmaceuticals, Inc.
Inovio is developing a new generation of vaccines, called DNA vaccines, to treat and prevent cancers and infectious diseases. Its SynCon® vaccines are designed to provide broad cross-strain protection against known as well as newly emergent unmatched strains of pathogens such as influenza. These vaccines, in combination with Inovio's proprietary electroporation delivery devices, have been shown in humans to be safe and generate best-in-class immune responses. Inovio's clinical programs include Phase II studies for cervical dysplasia/cancer, leukemia and hepatitis C virus and Phase I studies for influenza and HIV. Partners and collaborators include the University of Pennsylvania, Merck, ChronTech, National Cancer Institute, U.S. Military HIV Research Program, NIH, HIV Vaccines Trial Network, University of Southampton, and PATH Malaria Vaccine Initiative. More information is available at www.inovio.com.
This press release contains certain forward-looking statements relating to our business, including our plans to develop electroporation-based drug and gene delivery technologies and DNA vaccines and our capital resources. Actual events or results may differ from the expectations set forth herein as a result of a number of factors, including uncertainties inherent in pre-clinical studies, clinical trials and product development programs (including, but not limited to, the fact that pre-clinical and clinical results referenced in this release may not be indicative of results achievable in other trials or for other indications, that the studies or trials may not be successful or achieve the results desired, that results from one study may not necessarily be reflected or supported by the results of other similar studies and that results from an animal study may not be indicative of results achievable in human studies), the availability of funding to support continuing research and studies in an effort to prove safety and efficacy of electroporation technology as a delivery mechanism or develop viable DNA vaccines, the adequacy of our capital resources, the availability or potential availability of alternative therapies or treatments for the conditions targeted by the company or its collaborators, including alternatives that may be more efficacious or cost-effective than any therapy or treatment that the company and its collaborators hope to develop, evaluation of potential opportunities, issues involving product liability, issues involving patents and whether they or licenses to them will provide the company with meaningful protection from others using the covered technologies, whether such proprietary rights are enforceable or defensible or infringe or allegedly infringe on rights of others or can withstand claims of invalidity and whether the company can finance or devote other significant resources that may be necessary to prosecute, protect or defend them, the level of corporate expenditures, assessments of the company's technology by potential corporate or other partners or collaborators, capital market conditions, our ability to successfully integrate Inovio and VGX Pharmaceuticals, the impact of government healthcare proposals and other factors set forth in our Annual Report on Form 10-K for the year ended December 31, 2010, our Form 10-Q for the three months ended June 30, 2011, and other regulatory filings from time to time. There can be no assurance that any product in Inovio's pipeline will be successfully developed or manufactured, that final results of clinical studies will be supportive of regulatory approvals required to market licensed products, or that any of the forward-looking information provided herein will be proven accurate.
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