VIRxSYS report the results of its latest clinical trial, testing VRX496, a HIV-derived lentiviral vector that could represent a novel HIV gene therapy. The trial results also showed patients with multiple-drug resistant HIV responding well to the therapy.
News of this latest discovery comes after a multi-drug resistant strain of HIV was discovered in the US that did not respond to three classes of anti-retroviral medication, and also appeared to shorten the interval between HIV infection and the onset of AIDS.
The HIV-derived lentiviral vector has the disease-causing aspects of the virus removed, leaving behind a genetic delivery vehicle. This vector is then equipped with an anti-HIV genetic medicine consisting of a long antisense molecule targeted against the HIV envelope gene.
This antisense genetic treatment blocks HIV replication in CD4 T cells, which would otherwise be destroyed by the HIV virus. Without CD4 T cells, the immune system would collapse, allowing the onset of full-blown AIDS.
Gene therapy clinical trials have faced many hurdles in the past, most significantly with identifying an efficient vector to deliver an effective and permanent therapeutic payload. An important aspect to our therapy is that the high efficiency of lentiviral vector gene transfer, combined with the delivery of a genetic payload, instead of protein payload, overcomes two major obstacles that have hindered success in past gene therapy clinical trials.
The Phase I clinical trial was to determine the safety of the VRX496 therapy in patients failing two or more Highly Active Antiretroviral Treatment (HAART) regimens.
Each of the five patients had been dosed with a single infusion of VRX496, and none had experienced any serious adverse events related to the treatment. In addition to this, three patients who completed his/her one-year post-dosing assessment unexpectedly showed a clinically significant decrease in viral load, which is a measure of HIV's presence in the body.
The fourth and fifth patients had completed their six and three-month assessments, respectively, and their viral loads remained stable. The one-year post-dosing assessments of these two patients will be completed in July and September of this year.
In addition to these viral load findings, the CD4 T cells, typically destroyed by HIV, remain stable in the first patient and increased by 20 per cent and 35 per cent in the second and third patients, respectively. The fourth and fifth patients' CD4 T cell counts also remained stable.
"VIRxSYS' VRX496 therapy has the potential to become the next generation of HIV treatment. The patients in our clinical trial have multiple-drug resistant HIV, but nevertheless are responding well to this gene therapy," says Riku Rautsola, CEO-designate of VIRxSYS.
The results of this trial especially the impact on patient viral load and CD4 T cell counts suggest that the VRX496 is restoring a healthy immune system in these HIV patients. The potential is there for immunity to not only be enhanced for HIV but for other infectious pathogens.
For the 40 million people infected with HIV worldwide, the best hope for avoiding the consequences lies in treatment with active antiretroviral therapy, which consists of combinations of three or more drugs that inhibit HIV reverse transcriptase or protease. The benefits of HAART in reducing mortality are clear, but major questions remain about how best to use HAART and how to make it available to all who need it.
Current HAART regimens cannot cure the infection in most patients because the virus persists in a stable reservoir in resting memory CD4+ T cells. Because HAART is not curative, treatment of HIV infection is a lifelong challenge. Most infected individuals will ultimately have to depend upon HAART to avoid fatal immunodeficiency. Problems of drug resistance and drug toxicity make this an alarming prospect.
Based on these results, VIRxSYS plan to meet with the US Food and Drug Administration in early March 2005 to present Phase I results and discuss plans for a controlled, multi-centre, multi-dose trial. Based on this outcome, VIRxSYS would commence a Phase II study in the 2nd Quarter of 2005.
A separate Phase I/II clinical trial examining the potential role of VRX496 in extending HIV patients' drug holidays will be started by Phase I co-principal investigator, Dr Carl June of the University of Pennsylvania.