Date: 2016-02-25
Type of
information: Presentation of results at a congress
phase: 2a
Announcement: presentation of results at the Conference for Retroviruses and Opportunistic Infections (CROI) in Boston, USA
Company: Abivax (France)
Product: ABX464
Action
mechanism:
- splice modulating agent. ABX464 is a first-in-class, small molecule inhibiting HIV replication through the inhibition of the Rev protein activity and modulation of RNA splicing. In collaboration with the team of Professor Jamal Tazi at the CNRS in Montpellier, France, ABIVAX designed ABX464 to lead to a clinically relevant improvement in HIV therapy. Preclinical data in humanized mice demonstrated that ABX464 monotherapy had an antiviral effect that was sustained following treatment interruption (Campos et al, Retrovirology 2015 12:30). A prior food-effect study demonstrated a three-fold increase in parent drug exposure when administered with food, without a significant impact on active glucuronide metabolite.
Disease: HIV/Aids
Therapeutic
area: Infectious diseases
Country: Mauritius, Thailand
Trial
details:
- The randomized, double-blind placebo-controlled clinical study is being conducted in Mauritius. The trial is designed to assess the safety and efficacy of ABX464. 80 treatment-naïve patients will be enrolled into ten cohorts with six patients receiving ABX464 and two participants receiving placebo in each cohort. Five doses (25, 50, 75, 100 and 150mg) and two dosing frequencies (every day and every three days) will be tested. Treatment duration is two weeks and may be extended to three. The viral load will be monitored before, during and after treatment. The study's clinical endpoints are: safety, viral load in the blood and CD4 and CD8 cell counts.
Latest
news:
- • On February 25, 2016, Abivax presented data from the its Phase IIa study demonstrating the safety and potent viral reduction capacity of ABX464 in treatment-naïve HIV positive patients. Data were presented by Dr. Jean-Marc Steens, chief medical officer at Abivax, summarizing the findings published in an abstract entitled, “Early Evidence of Antiviral Activity and Safety of ABX464 in HIV Treatment Naïve Patients”, at the Conference for Retroviruses and Opportunistic Infections (CROI) in Boston, USA. The objective of the study presented at CROI was to evaluate the safety of ABX464 at ascending doses versus placebo in HIV-infected treatment naïve patients from Mauritius and Thailand. Patients were randomized into 5 successive cohorts of 8 patients each: 6 received 14 or 21 days of ABX464, and 2 received placebo. Successive cohorts received 25, 50, 75, 100 and 150 mg QD. The 25, 50 and 100 mg cohorts took the drug while fasting for 21 days; the 75 and 150 mg cohorts took the drug with food for 14 days. Viral load reduction of >0.5 log (>68%) was observed in 1/6 patients in the 75 mg cohort, 2/6 patients in the 100 mg cohort and 4/6 patients in the 150 mg cohort. There were no significant viral load changes in the 6 placebo patients from these cohorts.
- The only adverse events noted were nausea, vomiting and headache. All adverse events were grade 1 or 2 and all patients completed at least 14 days of treatment. The most common drug-related adverse events were headache, nausea, and vomiting. All occurred within the first 24 hours of dosing and diminished; no event was greater than Grade 2. Preliminary PK analysis suggest these events are related to Cmax. ABX464 monotherapy showed dose related antiviral activity with 4-of-6 patients in the 150 mg dose group achieving 0.5 log10 reduction by Day 14. Preliminary PK analysis does not differentiate 2 responders versus non-responders.
- A second phase 2a study with ABX464 will be conducted in Belgium, France and Spain,
- • On January 11, 2016, Abivax announced positive top-line efficacy and safety results from its Phase IIa clinical study (ABX464-003) in patients with HIV infection. The ABX464-003 clinical study was a randomized, double-blind, placebo-controlled Phase IIa monotherapy dose-ranging study in HIV infected patients who have not previously received antiviral drugs. Patient cohorts were administered ABX464 in increasing doses once daily for up to 3 weeks. Each dose cohort consisted of 6 patients treated with ABX464 and 2 patients receiving placebo.
A dose-dependent increase in the response rate to ABX464 monotherapy was observed in the study. The majority of patients who received the highest dose (150 mg) showed a viral load reduction of at least 0.5 log (greater than 68% reduction) during the treatment period. No such change was observed in any of the corresponding placebo patients. The safety data from this study indicate that ABX464 was well tolerated. There were no severe and/or serious adverse events that were ABX464-related. The observed adverse events (mainly headache, nausea and emesis) were predominantly mild and sometimes moderate in nature. Abivax will present more detailed results from this study at several scientific conferences in the coming months.
The primary goal of ABX464 clinical development is to optimize an ABX464-based treatment regimen that could result in a long-lasting functional cure upon treatment cessation in patients who respond to ABX464.
- • On November 30, 2015, Abivax announced that results of the first Phase IIa clinical trial of ABX464 in naive patients infected with HIV are expected in January 2016. Patients are currently being enrolled in Thailand and in Mauritius. This study is overseen by a Data Monitoring Board (DSMB) in charge of the safety aspects of the study, specifically authorizing each consecutive dose escalation. The DSMB has already reviewed safety data from the lower dose groups and authorized dose-escalation to the higher dose regimens, as planned in the study protocol. The high-level results of this blinded study are expected to become available in January of 2016. Abivax is currently planning a second phase 2a study in patients with HIV, to be initiated in France, Belgium and Spain. The double-blind trial will enroll 28 patients whose disease is controlled by treatment with boostered Darunavir. Patients will be randomized 3:1 to receive daily doses of either ABX464 at the highest tolerated dose from the currently ongoing study (21 patients) or placebo (7 patients). After 4 weeks of combination treatment, all therapies will be stopped, and the time to viral load rebound will be measured and compared between groups.
- • On February 2, 2015, Abivax, a leading clinical stage biotech company developing and commercialising anti-viral compounds and human vaccines, announced that enrolment has been initiated and the first HIV positive patient dosed in a Phase IIa clinical trial of ABX464. In pre-clinical reference models of HIV, ABX464 has proven its unique ability to induce a substantial reduction in viral load that persists for weeks after treatment arrest. Such an anti-viral effect has never been observed with existing treatments. With current HIV treatments, the virus starts multiplying again as soon as the drugs are withdrawn, which typically means daily, life-long treatment for patients. Additionally, in pre-clinical tests, the HIV virus did not develop any resistance to ABX464. Pending confirmation in clinical trials, this unique mode of action and preclinical data to-date suggest that ABX464 could induce long term control of the viral load and not induce HIV mutants that are resistant to treatment. It could also be less frequently administered over a shorter period than standard treatments; providing the potential to reduce healthcare costs and offer broader access to treatment.
- The randomized, double-blind placebo-controlled clinical study, which is being conducted in Mauritius, is the first one of ABX464 in HIV patients and is designed to assess the safety and efficacy of the compound. It follows the successful completion of a Phase I clinical study in human volunteers in December 2014, which demonstrated that ABX464 was generally safe and well tolerated and had a favourable pharmacokinetic profile. For the present study, 80 treatment-naïve patients will be enrolled into ten cohorts with six patients receiving ABX464 and two participants receiving placebo in each cohort. Five doses (25, 50, 75, 100 and 150mg) and two dosing frequencies (every day and every three days) will be tested. Treatment duration is two weeks and may be extended to three. The viral load will be monitored before, during and after treatment. The study's clinical endpoints are: safety, viral load in the blood and CD4 and CD8 cell counts. The study aims to allow Abivax to narrow the dose and frequency of administration for the subsequent clinical phase IIb study development planned for the second half of 2015.
Is
general: Yes
