Inovio Pharmaceuticals, Inc. (NYSE MKT: INO) today announced the release of preliminary clinical trial results by its collaborator ChronTech AS of their open label phase II clinical study of ChronVac-C®, ChronTech's vaccine to treat hepatitis C virus (HCV) infection. The study investigated the use of the ChronVac-C DNA vaccine administered with Inovio's MedPulserTM-DDS electroporation device followed by a drug regimen (ribavirin + PEG-interferon-a) in chronic HCV positive subjects. These initial results do not show a statistically significant difference so far between treatment outcomes of the vaccinated and non-vaccinated groups. The vaccinated group did display an excellent safety profile.
In this 29 patient phase II study, 17 patients were treated with two monthly vaccinations of ChronVac-C (500 ug) followed by interferon and ribavirin. In the control arm, 12 patients were treated with interferon and ribavirin alone. ChronTech has now made a first analysis 12 weeks after treatment. HCV viral load reduction or elimination is assessed by measuring HCV RNA levels. At treatment week 12, 71% of the pre-vaccinated group had less than 15 international units of HCV RNA compared to 58% in the non-vaccinated group; 65% were HCV RNA negative compared to 58% in the non-vaccinated group. There were no serious adverse events and the number of patients with moderate adverse events was statistically lower in the pre-vaccinated group than in the non-vaccinated group (p<0.05, Fishers exact test). There was no difference in mild adverse events between the groups.
In 2007, ChronTech initiated its phase I dose escalation (167, 500, 1500 mg) study using its ChronVac-C DNA vaccine targeting genotype 1a and NS3/4A antigens delivered with Inovio's MedPulser device. The treatment regimen of four vaccinations delivered with electroporation demonstrated transient reduction in viral load. In that study, a group of eight patients were subsequently treated with standard of care ribavirin plus PEG-interferon-a. Of this group, six patients (75%) achieved a complete early viral response (cEVR) and a sustained viral response (SVR), an encouraging result compared to typical medical observations of 40-50% response rates with the ribavirin-interferon drug regimen alone in genotype 1 patients. In contrast to the previous study, in this subsequent phase II study only two DNA vaccine administrations at the medium dose level used in the phase I study were used to assess the potential for a clinically meaningful result.
"The major hurdle to developing therapeutic vaccines for any disease area has been the inability to generate a meaningful level of functional T-cell response and, in the case of HCV, one that is directed to the liver. We have appreciated the opportunity in this collaboration to support ChronTech with our electroporation delivery technology and observe the impact of varying vaccine doses and regimens and their combination with standard of care on immune responses and HCV viral load," said Dr. J. Joseph Kim , Inovio's President and CEO.
"Inovio's extensive preclinical and clinical data generation and experience in advancing DNA vaccines across multiple disease areas have shown us that our effort to characterize and design highly optimized multi-antigen-targeting DNA vaccines and dosing, vaccination, and electroporation parameters was a necessary and successful step to achieve desired therapeutic immune responses. Our next-generation SynCon® vaccines and CELLECTRA® electroporation delivery devices have demonstrated best-in-class T-cell responses for HIV and cervical dysplasias caused by HPV and the ability to generate functional CD8 T-cells with antigen-specific killing activity in humans. Similarly, Inovio's proprietary HCV DNA vaccine therapy employing these next-generation technologies has achieved a scientific first by inducing highly functional T-cells in the liver in animal studies. There remains an important role for a potent therapeutic HCV vaccine in treating and managing this chronic disease. We look forward to initiating our planned phase I clinical study of Inovio's proprietary HCV DNA vaccine later this year."
Inovio's SynCon® DNA vaccine, INO-8000, is coded to produce the antigens NS3/4A, NS4B, and NS5A of HCV genotypes 1a and 1b, the most difficult-to-treat genotypes. This is one of the broadest spectrums of antigens targeted by any HCV vaccine or drug, including those under development, and creates a better possibility to induce the desired therapeutic immune response. Our proprietary DNA vaccines are uniquely designed to enhance gene expression and antigen secretion, processing, and presentation through a proprietary combination of DNA, RNA, and codon optimization techniques as well as the use of patent protected IgE leader sequences. Our CELLECTRA® electroporation device co-localizes vaccine delivery with the applied electric field and operates under more effective constant-current EP parameters. Together these next-generation technologies have generated levels of T-cells that are often orders of magnitude greater than competing technologies, including those using viral vectors and other facilitated delivery systems.
Inovio recently announced the completion of preclinical development of INO-8000, with data demonstrating the induction of functional T-cells in the liver published in PLOS ONE, and completion of cGMP manufacturing of clinical product. Inovio plans to initiate a phase I study of INO-8000 in 4Q 2013.