Fostemsavir-containing regimens remained generally well tolerated through 96 weeks of treatment, according to data from the BRIGHTE phase 3 trial. The trial evaluated fostemsavir in heavily treatment-experienced patients with multidrug resistant HIV-1, and for whom no viable antiretroviral therapy (ART) regimen could be determined. A subgroup analysis of week 96 outcomes from the BRIGHTE trial looking at the randomized cohort also found “remarkable efficacy with [fostemsavir] across a wide spectrum of heavily treatment-experienced patients including comparable and durable rates of virologic response in older, black and female participants compared to their counterparts.” These results were presented at the 10th IAS Conference on HIV Science, held July 21 to 24, in Mexico City, Mexico.
The BRIGHTE trial1 assigned participants into a randomized or nonrandomized cohort. Participants in both groups were heavily treatment-experienced patients who were failing a current ART regimen. Participants who did not undergo randomization had no remaining options for ART and no remaining options for treatment with a fully active approved compound. Those who underwent randomization had 1 or 2 remaining ART classes and ≥1 fully active available agent per class, but clinicians were unable to construct viable regimens for these patients from remaining agents. Both cohorts received 600 mg of open-label fostemsavir plus optimized background therapy for the duration of the study.
Overall results from the trial at week 96 found that 60% of randomly assigned patients achieved virologic suppression, which was an increase of 6% from week 48, despite continued attrition. Results also showed the mean increase in CD4 was 205 cells/μL. Among randomly assigned patients with baseline CD4 <200 cells/μL, levels increased to ≥200 in 67% and increased from <50 to ≥200 cells/μL in56%.
There were higher rates of severe adverse events and deaths reported at week 96 in the nonrandomized vs randomized participants. Overall, 38% of participants had a severe adverse reaction; 3% were drug related and 7% of participants discontinued because of adverse events. Complications of advanced AIDS and acute infection were attributed to most deaths in the trial.
A subgroup analysis based on demographic factors of the randomized cohort results2 showed that virologic responses at week 96 increased from week 48 and were comparable across most subgroups. Immunologic improvements were also comparable across all subgroups, including a mean increase of 240 cells/μL in participants with baseline CD4 counts <20 cells/μL. Further, 46% of patients with CD4 counts <20 cells/μL had a severe adverse event, whereas 27% of patients with CD4 counts ≥200 cells/μL had a severe adverse event.
Results from the overall BRIGHTE trial support continued development of fostemsavir as a potentially important treatment option for heavily treatment-experienced patients with multidrug resistant HIV. The subgroup analysis found clinically meaningful improvements in CD4 counts across all subgroups, even in those with the highest level of immunosuppression at baseline.
- Lataillade M, Lalezari J, Aberg J, et al. Week 96 safety and efficacy of the novel HIV-1 attachment inhibitor prodrug fostemsavir in heavily treatment-experienced participants infected with multi-drug resistant HIV-1 (BRIGHTE study). Presented at: 10th IAS Conference on HIV Science; July 21-24, 2019; Mexico City, MX. Abstract 3372.
2. Ackerman P, Aberg J, Molina JM, et al. A subgroup analysis of the week 96 efficacy and safety results evaluating fostemsavir in heavily treatment-experienced HIV-1 infected participants in the phase 3 BRIGHTE study: results from the randomized cohort. Presented at: 10th IAS Conference on HIV Science; July 21-24, 2019; Mexico City, MX. Abstract 4169.