Date: 2012-02-15
Type of information:
phase: 2b
Announcement: results
Company: Bionor Pharma (Norway)
Product: Vacc-4x
Action mechanism: Vacc-4x is designed to generate immune responses to conserved domains of p24 that are common to all strains of HIV. Sustained immune responses to p24 have previously been shown to delay HIV disease progression.
Disease: HIV-Aids
Therapeutic area: Infectious diseases
Country:
Trial
details: 136 patients participated in the five country trial, with two-thirds (93) randomized to receive Vacc-4x together with ART, while one-third (43) received a placebo injection and ART. Patients were immunized with Vacc-4x or placebo while on ART over a period of 28 weeks. This was followed by a period without treatment, lasting up to 24 weeks (until week 52).
Latest
news: Final review of phase IIb viral load data has been completed and confirms statistically significant 64% reduction of viral load “set point” (average of the last two viral load measurements before the end of the study) in patients receiving Vacc-4x compared to those given placebo, indicating a possible new option for patients and doctors. For patients that successfully completed the study (week 52), the placebo group (n=25) had a viral load set point of 61,900 cmL compared to the Vacc-4x group (n=56) that had a viral load set point of 22,300 cmL. This difference represents a reduction of 64% and is statistically significant (p =0.04). All values represent median. A subgroup comparison has been performed with only those patients who had a known viral load measurement before starting ART (pre-ART). The placebo group (n= 18) had no statistically significant difference between pre-ART viral load (52,731 cmL) and the viral load set point at the completion of the study (50,400 cmL, p= 0.98). In contrast, the Vacc-4x group (n=45) had pre-ART viral load of 60,470 cmL, compared to 24,150 cmL at study completion, resulting in a statistically significant reduction of 60% (p= 0.0001). The previously reported findings showing an association between viral load and HIV-specific immune responses are also confirmed. Patients with immune responses to p24 at study termination had a higher viral load set point in the placebo group (61,900 cmL) compared to the Vacc-4x group (22,925 cmL). HIV-specific immune responses resulted in increased viral load in the placebo subjects, whereas the Vacc-4x group had a significantly better viral control (p=0.048). Based on the conclusive phase IIb data, Bionor is studying several paths to guide the direction towards a Phase III pivotal trial, the final study before regulatory review and market entry: 2. Vacc-4x in combination with Revlimid® (Lenalidomide), for patients with unmet medical needs (study planned 1 H 2012). Based on the confirmed ability for Vacc-4x to lower viral load in HIV patients, Bionor will study the effect of combining Vacc-4x with Revlimid, for patients who are well controlled on ART but fail to regain immune competence (CD4 T-cell counts). By combining Vacc-4x with Revlimid, an immunomodulatory drug, Bionor`s researchers will determine whether patients experience improvement. 3. Vacc-4x in combination with Vacc-C5, to reduce viral load and the spread of infection. Vacc-C5 is designed to induce antibodies to HIV that can reduce HIV associated immune hyperactivation which leads to AIDS. Preclinical studies have shown that Vacc-C5 successfully induced antibodies against HIV in animal models such as rabbits and sheep. Bionor intends to conduct the first clinical study of Vacc-C5 in man in 2Q 2012. Subsequent to the Vacc-C5 phase I/II trial, Bionor intends to combine Vacc-4x with Vacc-C5, a treatment that can potentially revolutionize the management of HIV infections and could form the basis for both a therapeutic and a preventative vaccine.
The HIV viral load set point in patients given Vacc-4x was 60% lower than pre-ART (level before starting with standard medicine, ART). In the placebo group, no change compared to pre-ART was observed.
These final conclusions from the phase IIb, placebo-controlled, double-blind, international, multicenter trial, confirm initial findings of a statistically significant difference in viral load set point between Vacc-4x and placebo groups at the end of the study. The full results in addition to the final review of the immunological assessment are being prepared for publication in an international peer reviewed journal.
1. Vacc-4x revaccination of patients from the phase IIb study, to further reduce the viral load set point (study planned 1H 2012). Based on the statistically significant lowering of viral load after vaccination with Vacc-4x compared to before taking ART, Bionor researchers plan to re-vaccinate Vacc-4x patients from the IIB study to see if the viral set point can be reduced even further. Such an approach may eventually form a “functional cure,” meaning that HIV viral load is gradually reduced to lower levels following successive ART-free periods.
Bionor is furthermore investigating different options for administration of its vaccines.
An ongoing trial at Oslo University Hospital aims to reveal whether Vacc-4x given by nasal administration can provide equivalent effect compared to delivery by needle injection. Such administration will be important for cost and availability in both Western and especially developing countries. All patients have been successfully included in the trial and the results are expected in first half of 2012.
