PLoS ONE publishes review of AntiViral-HyperActivation Limiting Therapeutics clinical trial

Oct 22 2012

ViroStatics, a private Italian/American biopharmaceutical company developing novel therapeutics for viral and other chronic diseases, announced that a review of the first human clinical trial to test a new class of anti-HIV medications known as AntiViral-HyperActivation Limiting Therapeutics (AV-HALTs) has been published in the peer-reviewed journal PLoS ONE. The Phase 2a study demonstrated that markers of immune system hyperactivation driving HIV disease progression can be rapidly and effectively reduced by AV-HALTs, resulting in a proportional restoration of immune system damage.

“It has been more than thirty years since the first AIDS cases were reported”

"It has been more than thirty years since the first AIDS cases were reported," said Franco Lori, MD and CEO of ViroStatics. "Since these first reports, the field has made great advances against HIV. Yet, an unmet medical need remains - how to directly reduce the immune system's excessive response to the virus, a response that paradoxically becomes harmful over time."

"To test the AV-HALT concept in HIV, we developed VS411 as a two-drug combination product designed to accomplish two distinctive goals," Dr. Lori explained. "First, to reduce circulating virus as the currently approved HIV/AIDS medications do. Secondly, VS411 is the first of a new class of HIV antivirals that also directly target the inappropriately elevated level of immune system activation experienced by HIV-infected people. This excessive hyperactivation begins within the first weeks of HIV infection, lasts throughout the disease, and is now recognized as the driver behind immune system exhaustion, the loss of CD4⁺ T cells, non-AIDS events, and the onset of AIDS."

This second mechanism is so unique that drugs effectively accomplishing both goals are now known as a new class that ViroStatics has pioneered and named Antiviral-HyperActivation Limiting Therapeutics (AV-HALTs). To test the proof-of-concept that VS411, an AV-HALT containing both an antiviral and an anti-proliferative drug, could both inhibit viral replication and directly reduce markers of excessive immune system activation, a 28-day Phase 2a study followed traditional safety and efficacy parameters as well as measurements of four accepted markers of immune system hyperactivation - PD-1 (exhaustion), Ki-67 (proliferation), CD38 (activation), and HLA-DR (activation).

"This week's PLoS ONE paper reports Phase 2a data from our multinational trial," said Study Investigator Renato Maserati, MD, IRCCS Policlinico San Matteo Foundation, Infectious Disease Department, Pavia, Italy. "In this five-arm, dose-ranging study, once-daily VS411 was well-tolerated, produced significant reductions of HIV-1 RNA levels, increased CD4⁺ T cell counts, and led to significant, rapid, unprecedented reductions of immune activation markers after 28 days despite incomplete viral suppression and without inhibiting HIV-1-specific immune responses. These results were achieved in subjects mirroring the global pandemic: 50% female and 50% black from both the northern and southern hemispheres."

"It is encouraging to note that the reduction in excessive immune activation was achieved in only 28 days without complete viral load suppression, confirming the HALT activity of the VS411 formulation," added Dr. Lori. "In fact, after only 28 days of VS411 treatment, the median percentages of CD4⁺ and CD8⁺ T cells co-expressing CD38 and HLA-DR were significantly decreased, reaching levels similar to those seen in HIV-1-infected individuals receiving 20 months of traditional therapy. We believe AV-HALTs have the possibility of creating a true paradigm shift in the treatment of HIV/AIDS. With the AV-HALT proof-of-concept now established and using the two drug combination VS411 as the AV-HALT prototype, work is underway at ViroStatics to develop a newly identified family of compounds that exhibits both antiviral and HALT activities in a single molecule AV-HALT."