Successful Phase 1 Results
VRX496 is an autologous therapy that uses a patient’s own cells. Clinical sites collect white blood cells from individual patients by apheresis. VIRxSYS scientists purify the white blood cells to isolate CD4 T cells, which are transduced with VRX496. The genetically modified cells are expanded and reinfused into the patient.
When HIV enters CD4 T cells to replicate, the antisense payload of VRX496 is transcribed, which binds the virus and destroys it. The goal is to repopulate a patient’s immune system with genetically engineered cells that promote immunity against HIV and prevent the progression to AIDS. Although not a cure, VRX496 could improve the quality of life for HIV patients by bringing viral loads down to low levels. This approach could slow or even reverse a patient’s progression to full-blown AIDS.
In a Phase I trial, five chronic HIV patients, who had failed to respond to multiple standard antiretroviral drug regimens, received one infusion of VRX496. All patients showed stable or decreased viral loads as well as stable or increased immune responses to HIV antigens. Four of the five had stable or increased CD4 T cells. Some patients have maintained these positive outcomes for up to three years, and the genetically modified CD4 T cells remain in circulation.
In addition, no toxicities or adverse events related to VRX496 have been observed. The results are described in the November 7, 2006, issue of PNAS.
A Phase II study is under way in 40 chronic HIV patients to further establish the safety and tolerability of VRX496 and to determine the optimal dose.
Current anti-HIV drugs are small molecules that are highly toxic. Because HIV mutates rapidly, it often becomes resistant to conventional drug regimens taken by patients. VIRxSYS’ alternative gene therapy is designed to block all the mutation sites on HIV, preventing resistance. Thus VIRxSYS says that VRX496 overcomes the problems of toxicity and resistance.
Moreover, people who live with chronic HIV infections take an average of seven antiviral drugs daily to suppress the virus. VRX496, which is intended as a short-term therapy that offers long-term benefits, may be more convenient for patients by eliminating the need for multiple daily pills.
Carl June, M.D., who was a coprincipal investigator of the Phase I trial at the University of Pennsylvania Cancer Center in Philadelphia, started a new clinical trial. He’s treating early-stage HIV patients with six infusions over several weeks to determine whether VRX496 will allow them to stop standard HIV medications.