Bionor Pharma's Phase II Vacc-4x Data Published in the Lancet Infectious Diseases

OSLO, NORWAY--(Marketwired - Feb 11, 2014) - Bionor Pharma ASA (OSE: BIONOR) announces that the results from the randomized, multicenter, double-blinded, placebo-controlled Phase II trial with 135 patients of the Company's lead candidate Vacc-4x will be published in The Lancet Infectious Diseases and available online at www.thelancet.com as of today. An editorial in the same issue, "Shot in the HAART: a vaccine therapy for HIV," adds additional perspective on the value of the trial.

Therapeutic vaccines for infectious diseases are used in patients who already are infected with the goal of reducing or eliminating the circulating virus. The study showed that in subjects that completed a 6 month interruption of anti-retrovirals (ART), there was a log 0.44 (64%) reduction in median viral load set point in the Vacc-4x group compared to placebo. In addition, the Vacc-4x group showed a statistically significant reduction log 0.4 (60%) in viral load set point compared to subjects' pre-ART viral load values.

"Researchers are optimistic that the data offers clues for how such a vaccine could be optimized and offer the first new treatment modality in HIV in over coming years," said Richard Pollard, MD, Professor, Chief, Infectious Diseases, University of California Davis. "We need to understand why Vacc-4x appears to have worked much better in some patients than in others, in order to help expedite its regulatory approval."

"The publication of the Vacc-4x results by one of the world's most prestigious medical journals is an important milestone for Bionor Pharma and Vacc-4x," said Anker Lundemose, MD, PhD, CEO of Bionor Pharma. "We are grateful to the patients around the world who volunteered for this study in order to help build our understanding of how best to optimize this vaccine."

Reference: The safety and efficacy of the peptide-based therapeutic vaccine for HIV-1, Vacc-4x: a randomized, double-blind, placebo-controlled phase 2 trial, Pollard et al, The Lancet Infectious Diseases 2014. Online as of February 11, 2014.

HIV Set Point
The HIV set point is the viral load of a person infected with HIV. Viral load is measured as HIV viral RNA copies per ml of blood plasma.

About the Trial
The study was a phase II randomized, multicenter, double-blind, placebo-controlled multinational clinical trial of Vacc-4x. The trial enrolled 137 patients and was conducted at clinical trial sites in UK, US, Germany, Italy and Spain between July 2008 and June 2010. The 52-week follow-up period was completed in June 2011. The study is registered with Clinicaltrials.gov with the identifier NCT00659789.

The co-primary endpoints were time to resumption of antiretroviral therapy (cART) and changes in CD4 T-cell counts between Vacc-4x and placebo over time during treatment interruption.

Secondary endpoints were safety, viral load (VL) and immunogenicity (as measured by ELISPOT, and proliferation assays). 

The study enrolled individuals aged between 18 and 55 years, HIV-positive for at least one year, virologically suppressed on cART (VL less than 50 copies/mL for the last six months), pre-study CD4 cell count greater than or equal to 400x106/L, nadir (lowest ever) CD4 cell count greater than or equal to 200x106/L.

After a 28-week immunization period on cART, eligible patients were taken off cART and monitored for another 24 weeks. cART was resumed if CD4-counts fell below 350 cells/mm (3) or fell by more than 50% of the count at the start of the ART-free period, or if viral load increased above 300,000 copies/ml.

The proportion of participants that resumed cART between interruption of cART at week 28 and the end of the study at week 52 (34.1% Vacc-4x and 28.9% placebo) was not statistically significant (p=0.89). Similarly, the time to return to cART was not different (median 198 days Vacc-4x, 175 days placebo, p=0.77). The percentage change in CD4-counts between the two groups from week 28 to resumption of ART, alternatively week 52 showed a mean treatment difference of -5.71% which was not statistically significant (p=0.12).

Although the study did not meet its primary endpoints, a statistically significant difference in viral load at weeks 48 (Median 23100 copies/mL Vacc-4x (n=59), 71800 copies/mL Placebo (n=25), p=0.025) and 52 (Median 19550 copies/mL Vacc-4x (n=56), 51000 copies/mL Placebo (n=24), p=0.041) between the Vacc-4x and placebo groups was observed. For subjects that completed a 6 month treatment interruption, there was a 64% reduction in median viral load set point between the two groups which was statistically significant (Vacc-4x 22300 copies/mL, n=56; and placebo 61900 copies/mL, n=25; p=0.040) corresponding to a 0.44 log reduction. [viral load set point was defined as the mean of the last two VL measurements prior to cART resumption or at termination of the treatment interruption period i.e. week 52].

Pre-ART VL values were available for 63 of the participants that remained off cART for 6 months (Vacc-4x n=45, Placebo n=18). These correspond to historical viral load values taken within 6 months of cART initiation. There was a statistically significant reduction in median VL set-point (24150 copies/mL) compared to pre-ART values (60470 copies/mL) in Vacc-4x participants (n=45) (0.40 log reduction; p=0.0001). In contrast, the difference was not statistically significant for the placebo subgroup (n=18) where the VL set-point (median 50400 copies/mL) returned to approximate pre-ART levels (52731 copies/mL).

In subjects that completed a 6 month treatment interruption, an increase in proliferative assay responses over time to Vacc-4x antigens was observed in both CD4 and CD8 T-cell populations in the Vacc-4x group compared to placebo. ELISPOT responses to HIV p24^Gag (in the regions encompassed by Vacc-4x) were also measured. ELISPOT responders had a statistically significantly lower viral load set point in the Vacc-4x group than ELISPOT responders in the placebo group (Median 13425 copies/mL Vacc-4x (n=32), 76600 copies/mL Placebo (n=15), p=0.022).

Vacc-4x was found to be safe and well tolerated in the intention to treat population (ITT) (n=135).

Vacc-4x Further Trials and Analysis
33 patients from the trial are currently enrolled in the Company's Phase II Vacc-4x Reboost trial which investigates whether, upon booster immunizations, the viral load can be reduced even further on a second treatment interruption. The trial expects to read out Q1 2014.

Bionor Pharma has previously announces that a further exploratory ad hoc analysis of the Vacc-4x Phase II trial, identified anti-C5 antibodies as potential biomarker for the Company's lead vaccine candidate Vacc-4x. Biomarkers may predict how well an HIV infected patient will respond to Vacc-4x. Response to Vacc-4x was defined as the reduction in viral load following a 6 months scheduled interruption of standard HIV treatment (ART) compared to the subjects' historic viral load values (pre-ART values).

The analysis showed that patients more likely to respond to Vacc-4x, or responders, were characterized by pre-existing high levels of anti-C5 antibodies prior to Vacc-4x vaccination in the 2010 study. In conjunction with developing Bionor Pharma's second HIV vaccine candidate, Vacc-C5 (Phase I), a test to quantify the presence of antibodies to C5 and gp41 was developed. Vacc-C5 is a peptide construct corresponding to the C5 region of the gp120 protein plus a minor part of gp41 in HIV.

Patients whose baseline anti-C5 levels were above 4µg/ml had a median viral load reduction of log 0.94 or 88% (p=0.005, n=12) compared to the median pre-ART values. Patients with anti-C5 antibodies below 4µg/ml had a median viral load reduction of only 0.20 log or 37% (p=0.019, n=27) compared to pre-ART values.

Approximately 21 % of the patients that were analyzed in the 2010 Vacc-4x study had antibody levels above 4µg/ml prior to Vacc-4x vaccination.