J&J’s Covid-19 vaccine set to become third to US

FDA briefing documents show intriguing findings on asymptomatic prevention, though these are based on small numbers.

Trial Results

It looks like the 66% headline efficacy finding for Johnson & Johnson’s Covid-19 vaccine should be enough for its US approval. Briefing documents released by the FDA today concluded that JNJ-78436735, given as a single dose, was effective in preventing Covid-19.

However, perhaps the most intriguing finding from the detailed look at data from the Ensemble pivotal trial was related to asymptomatic infections, where a preliminary analysis found vaccine efficacy of 66%. Still, this result should be treated with caution as the number of participants included was small.

Overall, J&J’s candidate still looks a lot less impressive than Pfizer/Biontech’s Comirnaty and Moderna’s mRNA-1273, as evidenced by the cumulative incidence curve for JNJ-78436735. But, as well as being a single shot, J&J’s project has another advantage over the mRNA vaccines in that it does not need to be stored at sub-zero temperatures.

Source: FDA briefing documents

The FDA’s advisory committee is set to meet on Friday, but JNJ-78436735’s fate looks assured.

Today’s briefing documents confirmed what J&J disclosed last month: that its vaccine was 66% effective in preventing mild to moderate Covid-19 28 days after vaccination. In fact, protection began to kick in at 14 days, when incidence curves start to separate; vaccine efficacy after this time point was 67%.

J&J previously said that JNJ-78436735 provided complete protection against Covid-19 hospitalisations and death. However, while no hospitalisations occurred in the JNJ-78436735 arm at least 28 days after vaccination, there were two in the vaccine group at least 14 days after vaccination, both in participants aged 60 or over with comorbidities.

Efficacy of JNJ-78436735 in Ensemble
  Cases in active cohort Cases in placebo cohort Vaccine efficacy
Moderate to severe Covid-19* 66 193 66%
Severe Covid-19 at 28 days** 5 34 85%
Hospitalisation** 0 6 100%
Death 0 7 100%
Asymptomatic infections 18 50 66%
Moderate to severe Covid-19 in US 32 112 72%
Moderate to severe Covid-19 in South Africa 23 64 64%
Moderate to severe Covid-19 in Brazil 24 74 68%
Note: all at ≥28 days after vaccination. *Co-primary endpoint; other co-primary was moderate to severe Covid-19 after 14 days; **includes centrally confirmed cases only; Source: FDA briefing documents.

On the plus side, JNJ-78436735’s efficacy in South Africa, where the B1351 variant of Covid-19 is causing concern, looks better than the 57% figure in J&J’s interim analysis. 70% of the South Africa cases have been sequenced, and 95% of these involved the B1351 variant, the briefing documents confirm.

JNJ-78436735’s efficacy also looked good in those aged over 60, with the caveat that there were not enough patients in the 75-plus group to draw conclusions.

Upcoming readouts

J&J is also carrying out a pivotal trial of a two-dose regimen of JNJ-78436735, called Ensemble 2. Ahead of this, several other late-stage readouts for Covid-19 vaccines are due.

China’s Cansino has just confirmed earlier reports that a single dose of its candidate, Ad5-nCoV, showed 65% efficacy in a phase III study in South America, Russia and Pakistan. 

Astrazeneca is set to see data from its US phase III trial this quarter; also this quarter, Curevac will report pivotal Europe data with its mRNA vaccine candidate CVnCoV. So far, Curevac has only reported phase I results, with neutralising antibody levels with the highest dose, 12µg, in line with those observed in the sera of patients recovering from Covid-19.

Some have read those results as disappointing; in early trials, Pfizer/Biontech and Moderna both showed neutralising antibody levels exceeding those seen in convalescent sera. The studies are difficult to compare, given the different assays used, but it should not be long until it becomes apparent whether CVnCoV is as good as the mRNA frontrunners.

Selected upcoming late-stage Covid-19 vaccine readouts
Company Project Trial name/details N Trial ID Timing
Astrazeneca AZD1222 US ph3 30,000 NCT04516746 Data due Q1 2021
Curevac CVnCoV Herald, Europe ph2/3 36,500 NCT04652102 Data due Q1 2021
    Europe ph3, healthcare workers 2,500 NCT04674189 Primary completion Jun 2021
Novavax NVX-CoV2373 Prevent-19, US/Mexico ph3 30,000 NCT04611802 Data due Q2 2021
Clover/Dynavax SCB-2019 (Covid-19 S-Trimer) Europe/ROW ph2/3 22,000 NCT04672395 Interim analysis due mid-2021
Glaxo/Medicago CoVLP (coronavirus-like particle Covid-19 vaccine) US/Canada ph2/3 31,000 NCT04636697 Primary completion Dec 2021
Johnson & Johnson JNJ-78436735 Ensemble-2, US ph3 (two-dose regimen) 30,000 NCT04614948 Primary completion May 2022
Source: EvaluatePharma & company statements.

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