Johnson & Johnson said Tuesday that a large, global study showed its Covid-19 vaccine is more effective when given as a two-dose regimen, and that other data indicate the efficacy of the vaccine does not wane.
The two-dose regimen prevented 75% of moderate to severe Covid cases in all countries where it was tested — and 94% of such cases in the United States, where fewer troublesome variants of the SARS-CoV-2 virus circulated at the time the trial was underway. Importantly, the two-dose regimen was 100% effective against severe disease.
It appears J&J may use the data to argue in favor of making a booster broadly available to people who received the one-dose vaccine six months ago or more. A press release from the company did not say so explicitly, but stated J&J had submitted the data to the Food and Drug Administration and plans to submit them to other regulators and the World Health Organization.
The data could also help increase use of the vaccine in the U.S. and globally. Currently, in the U.S., it is the least-often administered of the Covid vaccines authorized or approved by the Food and Drug Administration. According to the Centers for Disease Control and Prevention, 14.6 million Americans have been inoculated with the Johnson & Johnson vaccine, compared to 67.7 million with the Moderna vaccine and 99.3 million with the Pfizer-BioNTech vaccine.
In its press release, J&J argued that available data, in aggregate, show both that the effectiveness of its single-shot vaccine does not wane and that adding a booster dose will make the vaccine more effective.
“It is critical to prioritize protecting as many people as possible against hospitalization and death given the continued spread of COVID-19 and rapidly emerging variants. A single-shot COVID-19 vaccine that is easy to use, distribute and administer that provides strong and long-lasting protection is crucial to vaccinating the global population,” Paul Stoffels, J&J’s chief scientific officer, said in a statement. “At the same time, we now have generated evidence that a booster shot further increases protection against COVID-19 and is expected to extend the duration of protection significantly.”
Like much of the vaccine data during the pandemic, summary data of the J&J two-dose study were made public in a press release, not a scientific publication. Companies feel obligated to release summary data of clinical trials immediately as a result of regulations meant to prevent insider trading, but this often means data are made public without details scientists would want to vet them.
When J&J began trials of its vaccine, developed with researcher Dan Barouch of Harvard Medical School, it said that it believed a single-dose vaccine would provide advantages in a pandemic. When results were released in January, the vaccine’s efficacy against moderate to severe disease was 66%. Although researchers cheered that benefit, it was lower than the 94% efficacy shown by both the Pfizer-BioNTech and Moderna vaccines.
The J&J vaccine rollout was bedeviled by other issues. There were supply problems. And then regulators paused the use of the vaccine for 10 days to get a clearer idea of a rare side effect, thrombosis with thrombocytopenia syndrome, that causes both bleeding and the formation of dangerous blood clots at the same time. The vaccine returned to use in April.
At the same time as it was organizing its first study, ENSEMBLE 1, Johnson & Johnson also planned a second 30,000-patient study, ENSEMBLE 2, in which volunteers would receive two doses 56 days apart. Part of the reason for the long interval is that there was some data indicating that J&J’s vaccine platform, which uses a modified virus called adenovirus, does not work as well when doses are given too close together.
In this study, there were 14 cases of moderate-to-severe Covid in the vaccine arm compared to 52 in the placebo arm (that works out to 75% efficacy) and zero cases of severe or critical Covid in the vaccine arm compared to eight in the placebo arm. In the U.S., there was one case of moderate-to-severe Covid in the vaccine arm and 14 in the placebo arm.
J&J also released further results from the ENSEMBLE 1 study of the one-dose vaccine. There were 433 cases of moderate-to-severe Covid in the vaccine arm, compared to 883 in the placebo arm — an efficacy of 53%. The efficacy against hospitalizations remained high, at 76%. (There were 16 cases in the vaccine arm and 64 in the placebo arm.)
Giving two doses instead of one increased antibody levels four- to six-fold. But the increase in antibody levels was much higher when the doses were spaced much further, and a booster was given at six months, J&J said. At six months, antibody levels increased nine-fold after one week and were 12-fold higher four weeks after the booster.
J&J also included a link to a paper, which has not been peer-reviewed, using claims from an insurance company to analyze the efficacy of the one-dose vaccine in practice in 390,000 people who received the J&J vaccine compared to 1.52 million who were matched based on age, sex, time, ZIP code, and risk factors that might predict Covid outcomes. These data showed a vaccine effectiveness of 79% for Covid-19 diagnoses and 81% for Covid-related hospitalizations. J&J argues that this shows that the efficacy of the vaccine was stable.
The data appear to set the stage for a discussion over whether the J&J vaccine should be thought of as a two-dose regimen, with the doses given six months apart. In order for that to happen, regulators will convene open meetings and much more detailed data will need to be made public.
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