The primary analysis of Johnson & Johnson's Phase 2b HIV vaccine clinical trial known as the Imbokodo study has been stopped, after showing that the investigational vaccine regimen did not provide sufficient protection against HIV infection in a population of young women in sub-Saharan Africa who were at high risk of acquiring HIV. The vaccine was just 25% effective in preventing HIV infection over a period of two years, short of a goal of 50% efficacy, according to a statement.
Based on these results, said Johnson & Johnson, the Imbokodo study will not continue.
The studyʼs halt is another setback in efforts to control HIV, a treatable yet potentially lethal disease that afflicts almost 38 million people worldwide. About 1.5 million were infected last year. While people can live healthy lives with the virus, prevention with a vaccine still appears tantalisingly out of reach.
In parallel to the Phase 2b Imbokodo HIV vaccine trial, Janssen is sponsoring the ongoing Phase 3 Mosaico study, which is testing the safety and efficacy of a different composition of the HIV vaccine regimen among men who have sex with men (MSM) and transgender individuals. This study is being conducted in the Americas and Europe where different strains of HIV are circulating. Given these differentiating factors and after consultations with the Mosaico study independent Data and Safety Monitoring Board (DSMB), it was decided that the Mosaico study will continue at this time.
“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 Dr Paul Stoffels, chief scientific officer at Johnson & Johnson.
Regarding the Mosaico study, he said the trial is sufficiently different that it still stands a chance of success. The study enrolled a male and transgender population where the spread of HIV is less intense and transmission patterns are different. The patients receive six shots of a vaccine regime that has a slightly broader spectrum, he said.
Despite the Imbokodo study setback, Stoffels said heʼs optimistic that the limited efficacy of the vaccine can help scientists advance towards a treatment thatʼs more effective. Study participantsʼ immune responses will be analysed to better understand why some were protected and others were not, he said.
“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.”
What the Imbokodo data tell us
The Imbokodo vaccine regimen was administered to participants through four vaccination visits over one year. The primary analysis was conducted 24 months after participants received their first vaccinations. 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%.
“The high incidence of HIV among young women in sub-Saharan Africa reminds us that, despite great progress made in treatment and prevention, HIV remains a major health challenge for the region,” said Professor Glenda Gray, president and chief executive officer, South African Medical Research Council (SAMRC) and Imbokodo’s Protocol Chair. “This underscores the need to apply the knowledge that will be gained from this trial to continue to advance the pursuit of a global HIV vaccine.”
The Imbokodo study tested an investigational HIV regimen with an adenovirus vector containing four mosaic immunogens (Ad26.Mos4.HIV) at four vaccination visits over one year. The Imbokodo regimen contains a soluble protein component (Clade C gp140, adjuvanted with aluminum phosphate) which is administered at vaccination visits three and four.
The ongoing Phase 3 Mosaico study 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.
Protecting women from HIV infection “continues to be a huge global priority”, said Mitchell Warren, executive director of Avac, an HIV vaccine advocacy organisation. “Seeing that this product isnʼt going to be a viable option for women at risk is a disappointment.”
In a BusinessLIVE article, he said J&Jʼs work on an HIV vaccine has been encouraging, as it is the first major drugmaker in the field to make major progress since Merckʼs trial of a promising shot failed almost 15 years ago. The success of J&Jʼs adenovirus-based technology in its Ebola and Covid-19 vaccines also boded well, he said.