Johnson & Johnson pulls HIV vaccine trial in Africa; but pledges to continue with Phase 3 Mosaico study
The HIV vaccine candidate was developed using the same AdVac viral vector platform as the company’s COVID-19 vaccine.
The Imbokodo study was run among young women in sub-Saharan Africa at high risk of acquiring HIV. The investigational adenovirus vector vaccine vaccine was found to have a favorable safety profile with no serious adverse events; but did not meet its primary endpoint with a vaccine efficacy of only 25.2%.
The study was run by Janssen and funded by the Bill & Melinda Gates Foundation (BMGF) and the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.
“The development of a safe and effective vaccine to prevent HIV infection has proven to be a formidable scientific challenge,” said NIAID Director Anthony S. Fauci, M.D. “Although this is certainly not the study outcome for which we had hoped, we must apply the knowledge learned from the Imbokodo trial and continue our efforts to find a vaccine that will be protective against HIV.”
The vaccine in the Imbokodo study is based on “mosaic” immunogens—vaccine components designed to induce immune responses against a wide variety of global HIV strains. The vaccine candidate uses a strain of common-cold virus (adenovirus serotype 26, or Ad26) to deliver four mosaic antigens to spur an immune response.
Imbokodo, a Phase 2b proof-of-concept efficacy study of the vaccine, began in 2017, reached full enrollment in 2019 and completed vaccinations on June 30, 2020. The study enrolled approximately 2,600 young women across five countries in sub-Saharan Africa, a region where women and girls accounted for 63% of all new HIV infections in 2020. The study took place at 23 trial sites in Malawi, Mozambique, South Africa, Zambia and Zimbabwe.
The Imbokodo vaccine regimen was administered to participants through four vaccination visits over one year; with the primary analysis 24 months after the first vaccination. The study’s primary endpoint was based on the difference in number of new HIV infections between the placebo and vaccine groups from month seven (one month after the third vaccination timepoint) through month 24.
These data found that through 24 months of follow up, 63 of 1,109 participants who received placebo compared to 51 of 1,079 participants who received active vaccine acquired HIV. This analysis demonstrated a vaccine efficacy point estimate of 25.2% (95% confidence interval of -10.5% to 49.3%).
Further analysis of the Imbokodo study will continue, and the study is thought to have provided sufficient data for further immunological correlates research.
Mosaico study to continue
The Imbokodo vaccine study tested an adenovirus vector containing four mosaic immunogens (Ad26.Mos4.HIV) at four vaccination visits over one year.
The regimen contained a soluble protein component (Clade C gp140, adjuvanted with aluminum phosphate) which was administered at vaccination visits three and four.
The ongoing Phase 3 Mosaico study, however, is testing a different investigational vaccine regimen that involves the administration of a mosaic-based mixture of soluble proteins (Clade C/Mosaic gp140) at vaccination visits three and four.
Furthermore, the study is being conducted among men who have sex with men (MSM) and transgender individuals; in the Americas and Europe where different strains of HIV are circulating.
Given these differentiating factors and following consultations with the Mosaico study independent Data and Safety Monitoring Board (DSMB), it was decided that the Mosaico study will continue at this time.
Having started in 2019, the study has a target enrolment of 3,800 individuals aged 18-60. The study is expected to be completed in March 2024.
“We are extremely grateful to the women who volunteered for the Imbokodo study, and to our partners, including the people on the frontlines, all of whom are contributing every day to this enduring quest to make HIV history,” said Paul Stoffels, M.D., Vice Chairman of the Executive Committee and Chief Scientific Officer at Johnson & Johnson.
“HIV is a unique and complex virus that has long posed unprecedented challenges for vaccine development because of its ability to attack, hijack and evade the human immune system. While we are disappointed that the vaccine candidate did not provide a sufficient level of protection against HIV infection in the Imbokodo trial, the study will give us important scientific findings in the ongoing pursuit for a vaccine to prevent HIV. We continue to stand in solidarity with people living with and vulnerable to HIV, and remain committed to furthering our research against this devastating virus.”
Johnson & Johnson has been working on HIV prevention and care for 25 years, having played a role in bringing nine therapeutics to people living with HIV. It started work on a potential HIV vaccine in 2005.