Inovio achieves positive results in Phase I PENNVAX-B study for HIV

Nov 18 2010

Inovio Pharmaceuticals, Inc. (NYSE Amex: INO), a leader in the development of therapeutic and preventive vaccines against cancers and infectious diseases, announced today that it has achieved high vaccine-induced response rates and strong magnitude of immune responses in its Phase I clinical study of PENNVAX™-B, a DNA vaccine for the prevention of HIV infection. Similar to recently reported results from a Phase I clinical study of Inovio's therapeutic DNA vaccine for cervical cancer, the response rates and magnitude of responses achieved in this study are significantly higher than those seen previously with other DNA vaccine trials. Dr. Spyros Kalams, principal investigator for the study and Immunology Director of the Vanderbilt Center for AIDS Research at Vanderbilt University Medical Center, presented the interim immune response and safety data at the Annual HIV Vaccine Trials Network (HVTN) Conference being held November 15-17 in Seattle, WA.

“The preliminary immune response data from this novel DNA-based vaccine are indeed very encouraging. We look forward to our continuing work with Inovio to develop the potential of this promising vaccine candidate.”

Inovio previously reported data from non-human primates demonstrating up to a 100-fold enhancement in immune responses resulting from the vaccine when delivered via in vivo electroporation compared to syringe injection without electroporation. This study, designated HVTN-080, involved vaccination of 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 is a SynCon™ DNA vaccine that targets HIV gag, pol, and env proteins. This randomized, double-blind, multi-center study is being 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 HVTN, at several clinical sites.

Of the 48 total volunteers, eight subjects received a placebo, 10 subjects received a 1 mg dose of PENNVAX™-B vaccine, and 30 subjects received a 1 mg dose of PENNVAX-B along with IL-12 DNA. The IL-12 for this study (Genevax-IL-12), manufactured under a contract with DAIDS, was provided by Profectus Biosciences. All volunteers received vaccine or placebo administered 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).

Preliminary data from the trial reported at the meeting included safety data from all trial participants (48) and immunogenicity data from 38 out of 40 samples from vaccine recipients post-second-dose and from 31 out of 40 samples from vaccine recipients post-third-dose. The data indicate that antigen-specific T-cell responses were generated by the vaccine in a majority of subjects. Either CD4+ or CD8+ or both T-cell responses were observed against at least one of the vaccine antigens in 61% (23 out of 38) of evaluated subjects after two vaccinations. After three vaccinations, 84% (26 out of 31) of evaluated subjects had positive T-cell responses.

Notably, after three vaccinations:

• 67% (6 out of 9) of evaluated subjects receiving PENNVAX-B and 91% (20 of 22) of evaluated subjects receiving PENNVAX-B + IL-12 were observed to have generated antigen-specific T-cell responses (either CD4+ or CD8+).
• Antigen-specific CD4+ T-cell responses were generated by the vaccine in 70% of evaluated vaccine recipients (21 out of 30).
• Significantly strong antigen-specific, CD8+ T-cell responses were also generated by the vaccine in 55% of evaluated vaccine recipients (17 out of 31).
• 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 generally safe and 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. Kalams stated, "The preliminary immune response data from this novel DNA-based vaccine are indeed very encouraging. We look forward to our continuing work with Inovio to develop the potential of this promising vaccine candidate."

Dr. J. Joseph Kim, Inovio's President and CEO, said: "After recently announcing best-in-class immunogenicity data from our clinical trial for our cervical cancer DNA vaccine using the same technology platform, we are pleased to again see very strong T-cell immune responses from this vaccine platform for a different disease, and particularly a disease with unmet needs like HIV. They are amongst the highest immune responses seen in other HIV vaccine trials either with DNA or other vaccine platforms including proteins and viral vectors. However, unlike viral vectors, DNA vaccines do not induce unwanted immune responses against the carrier. Taken together these results further support the prospect that Inovio's DNA vaccine and delivery platform could play an important role in developing new vaccines and therapies for major diseases like cancer and HIV."

In addition to the interim ICS results presented at the meeting, the complete immunogenicity data including data from the few remaining unanalyzed samples and additional antibody and T-cell results based on ELISpot assays as well as the end-of-study safety data are expected in 2Q 2011.

Source: Inovio Pharmaceuticals, Inc.