Clinical Development of Vacc-4x
After further analyses of the international, randomized, double-blind, placebo-controlled multi-center phase IIb study of Bionor Pharma's therapeutic HIV-vaccine candidate, Vacc-4x, the Company reports an unexpected statistically significant reduction in viral load (amount of HIV virus) at the end of the study period for patients on the vaccine compared to the placebo group.
The study was designed to test HIV-patients' ability to stay off anti-retroviral therapy (ART) after having been immunized with Vacc-4x. Although the study did not meet its primary endpoints, as announced October 1, the findings from the additional analysis discovered that treatment difference with regard to viral load was statistically significant both within the study period and when compared to the viral load prior to ever starting ART. In patients who received immunization, viral load never returned to its pre-ART level, which normally happens when being taken off ART.
Due to the new findings, the Company has reversed its decision to stop development of Vacc-4x. Along with upcoming immunological data, these findings are expected to become the basis for the future positioning of Vacc-4x as a viable therapeutic HIV-vaccine.
Clinical Development of Vacc-4x
Vacc-4x has undergone several pre-clinical and clinical studies:
Pre-clinical: Vacc-4x was shown to be free of acute toxicities that would preclude its development
Phase I – Safety: 11 chronically HIV-infected subjects enrolled at Haukeland University Hospital in 1999 - no serious adverse events occurred.
Phase IIa - Drug Holiday: 40 chronically HIV-infected subjects enrolled in a single center, open-label study at Oslo University Hospital in 2002. The results, when compared to 52 similar patients selected from a Dutch academic Observational Cohort (Athena), showed that while 25% of the patients from the Athena study remained off ART for 48 weeks, 75% of the patients in the Phase IIa trial remained off ART. The median time off ART for the 38 patients who completed the Phase IIa trial was 31 months, compared to 4 months in the Athena study.
Phase IIa - Re-vaccination study: Baseline blood data from 26 subjects from the original phase IIa study conducted in 2002/03 were analyzed showing at least seven years memory and T-cell killing activity in approx. 50% of the patients. In the 26 volunteers that were re-immunized it was demonstrated that immune memory of Vacc-4x can be safely and effectively reactivated following re-immunization, resulting in improved anti-viral responses. Two thirds of study volunteers responded to Vacc-4x. The study also showed that Vacc-4x is capable of triggering the specific T-cells of the immune system that function to seek out and kill infected cells (CD8+ killer T-cells), which is the objective of a successful T-cell vaccine.
Phase IIb - Drug Holiday: A randomized, double-blind, placebo-controlled, international multi- center phase IIb clinical study in 135 HIV-positive subjects who were clinically stable on ART. Patients were randomly enrolled in a 2:1 ratio into one of two treatment groups receiving either Vacc-4x immunization or placebo injection while on ART. At week 28 eligible subjects whose CD4+ count was at least 350 cells per mm3, were taken off ART and followed for an additional 24 weeks. The results of this study are expected in September/October 2010.