Date: 2016-06-17
Type of information: Interim results
phase: 2b-3
Announcement: interim results
Company: Abivax (France)
Product: ABX203
Action
mechanism: therapeutic vaccine. ABX203 is a therapeutic vaccine candidate composed of 2 recombinant proteins from HBV, the surface antigen (HBsAg) and the nucleocapsid (core) structure (HBcAg). ABX203 has successfully been tested in a phase clinical trial in healthy volunteers as well as in phase I study and two phase 2 studies in patients with chronic hepatitis B disease. ABX203 is formulated as a nasal spray solution and as a solution for sub-cutaneous injection. ABX203 is the first results of the collaboration with Cuban life science excellence. It has been acquired by Abivax from the Centre for Genetic Engineering and Biotechnology (CIGB) in Cuba. Abivax owns distribution rights for ABX203 for more than 80 territories in Asia, Europe and Africa. They were licensed in 2013 from the Center for Genetic Engineering and Biotechnology (CIGB, Havana, Cuba) following the completion of successful phase I, I/II and III clinical trials run by CIGB in Cuba and Bangladesh. These studies showed that ABX203 was well tolerated and had an antiviral effect similar to that of PEGIFN? but that this effect on HBV viral load was, in contrast with PEG-IFN?, sustained for at least 6 months after treatment cessation.
Disease: hepatitis B
Therapeutic area: Infectious diseases
Country: Australia, Hong Kong, New Zealand, Republic of Korea, Singapore, Taiwan, Thailand
Trial
details: The ABX203 phase IIb/III study is an open-label, randomized, comparative study designed to assess the efficacy of ABX203 to maintain control of Hepatitis B disease after cessation of nucleotide analogs, in particular in controlling viral load for a much longer period of time when compared to current treatment options. This study is ongoing in seven Asian/Pacific countries (Taiwan, HongKong, Thailand, Singapore, South Korea, Australia and New-Zealand). The study has recruited 261 patients with HBeAg negative active chronic hepatitis B. In this large scale controlled and randomized study, one group of patients will receive ABX203 for 24 weeks, in addition to the current standard of care (nucleoside analogues, NUCs, along with alpha interferon); therapy will be stopped after 24 weeks. These patients will be evaluated against a control group receiving NUCs only. The study’s primary efficacy endpoint is the percentage of subjects with viral load. (NCT02249988)
Latest
news: * On June 17, 2016, Abivax announced that a futility analysis on the primary end-point of its ABX203-002 trial, a Phase IIb/III trial of ABX203 in chronic hepatitis B patients, determined that the trial is unlikely to reach its primary endpoint. * On February 26, 2015, Abivax announced that it has dosed in New Zealand the first patient in a Phase IIb/III clinical trial of ABX203 which is taking place in several countries of the Asia-Pacific region. The study is designed to assess whether ABX203 can deliver a significant improvement in the treatment of chronic hepatitis B (CHB) via controlling viral load for a much longer period of time when compared to current treatment options. The pivotal Phase IIb-III study is expected to be conducted at 50 clinical centres in 7 countries in the Asia Pacific region. The study aims to recruit approximately 230 patients with HBeAg negative active chronic hepatitis B. The results from this Phase IIb-III study are expected in Q3 2016. A positive outcome from this study is expected to allow Abivax to file for marketing approval in certain Asian countries.
The ABX203-002 study is an open-label, randomized, comparative study designed to assess the efficacy of ABX203 to maintain control of the hepatitis B virus after cessation of nucleotide analogs, in particular in controlling viral load for a much longer period of time when compared to current treatment options. This study is ongoing in seven Asian/Pacific countries (Taiwan, Hong-Kong, Thailand, Singapore, South Korea, Australia and New-Zealand). In this large scale controlled and randomized study, where 276 subjects were enrolled as of September 2015, one group of patients received ABX203 for 24 weeks, in addition to the current standard of care (nucleoside analogues, NUCs). All therapy was stopped after 24 weeks, and these patients are evaluated against a control group receiving NUCs only. The study’s primary efficacy endpoint is the percentage of subjects with viral load <40 IU/mL at week 48, i.e 24 weeks after the treatment with ABX203 has been completed. An unscheduled futility analysis was initiated because of a recent increase in the patients’ drop out rate related to viral escape. A futility analysis is conducted during an ongoing clinical trial to describe the probability of a study to reach its primary endpoint. The result of this analysis shows that a positive outcome of the study regarding its primary endpoint is unlikely.
The Data Safety and Monitoring Board (DSMB) of study ABX203-002 was convened. The DSMB has recognized the good safety profile of ABX203 and recommended that the study should continue as per protocol, to monitor patients 24 weeks post-treatment in order to continue to assess their viral load and to have a comprehensive view of the secondary endpoints. Investigators, health authorities and patients are being informed of the conclusions of the DSMB. In a previous Phase II study, with a different design and carried out in Asia, treatment-naïve patients with chronic hepatitis B were administered ABX203 as monotherapy. That study established a significantly longer period to viral rebound as compared to patients receiving Peg-Interferon Alpha.
The future development of ABX203 is under review, including the usefulness of an adjuvant boosting the response to this immunotherapy, as well as new administration schedules and therapeutic combinations that may be evaluated via other preclinical and, potentially, clinical testing.
* On September 24, 2015, Abivax announced that it has completed enrollment of all 266 subjects into its pivotal Phase IIb/III clinical trial of ABX203, aimed at demonstrating the safety and efficacy of this therapeutic vaccine candidate for the treatment of patients with chronic hepatitis B disease. Study results are expected in the fourth quarter of 2016.
