Confidence renewed as new COVID-19 vaccines demonstrate protection against emergent strains and efficacy with a single-dose regimen
With the emergent COVID-19 strains at the front of investors’ minds as the pandemic has evolved since the beginning of 2021, we take confidence from data reported last week by Johnson & Johnson (JNJ) and Novavax (NVAX) reinforcing the belief that multiple vaccines will be required to bring us out of lockdowns and back to normality.
On Friday 29 January, JNJ reported impressive top-line data for its global Phase III ENSEMBLE trial for a single-dose of its COVID-19 vaccine (Ad26.COV2.S), with 66% effectiveness (in 43,783 participants) in preventing molecularly confirmed moderate to severe infections 28 days after vaccination. It is particularly noteworthy that it was effective against the new emergent strains, with the relative effectiveness of 72% in the US, 66% in Latin America and 57% in South Africa. Although the headline 66% might not appear to be as impressive compared to the headline data reported by Moderna (>90%), Pfizer/BioNTech (>90%) or AstraZeneca/Oxford University (up to 90%) in November 2020, we highlight these data are for a single-dose regimen and encompass its protective effect against the emergent COVID-19 strains that were more prevalent in the Phase III ENSEMBLE trial; we should not compare apples to oranges. What is particularly impressive, in our opinion, is that these data suggest JNJ’s single-dose regimen was 100% effective in preventing hospitalisation or death due to COVID-19 after 28 days, irrespective of geography or strain. A second Phase III trial is investigating the potential additive benefit of a second dose, but it seems unlikely this will be necessary or even adopted while the pandemic is ongoing, given the apparent logistical issues two-dose vaccines are facing.
Submission of an Emergency Use Authorization (EUA) to the FDA is expected next week, with other regulatory submissions expected shortly thereafter. JNJ has guided it has capacity to manufacture and distribute c 1bn doses globally through conventional cold chains. Subject to approval, JNJ will supply 100m doses to the US by end-June (option for purchase 200m additional doses), whereas the EU has a supply agreement for 200m doses (option for 200m additional doses). Agreements are also in place to supply 30m doses to the UK (option for 22m additional doses) and 38m doses to Canada. JNJ has also committed to allocating up to 500m doses to lower income countries with delivery beginning mid-2021. It is yet to be seen if JNJ can keep up with its promised schedule.
On Thursday 28 January, NVAX reported strong efficacy for its two-dose COVID-19 vaccine (NVX-CoV2373), which also showed it was effective against the emerging strains from the UK and South Africa. The headline results came from an interim analysis of the UK Phase III trial where the vaccine achieved an impressive 89% efficacy (based on PCR-confirmed symptomatic COVID-19 in 14,049 participants), despite over 50% of cases being attributable to the now-predominant more transmissible variant found in the UK. NVAX initiated a rolling submission to UK MHRA in mid-January and, following the final analysis (expected at c.100 cases), believes its first EUA could occur in the next two or three months. NVX-CoV2373 proved slightly less effective (60%) in the Phase IIb study in South Africa, where more than 90% of the 29 confirmed cases of COVID-19 were attributable to the new variant found in the region. Although the vaccine still met its primary endpoint, efficacy was likely depressed by the increased prevalence of a variant, which is potentially more resistant to neutralising antibodies.
NVAX prudently initiated development of new constructs against the emerging strains at the start of the year and will shortly select optimal candidates for a booster and/or bivalent vaccine against the new strains. It expects these new vaccines to enter clinical testing in Q221. NVAX’s vaccine is also able to be distributed through conventional cold chains and under initial supply agreements and it has guided it has capacity to manufacture over c 2bn annualised doses once it reaches full capacity later in 2021. The UK and US have secured 60m and 100m doses respectively, due for delivery later this year, again subject to approval. The ongoing US Phase III PREVENT-19 trial has randomised more than 16k participants and expects to reach its 30k target during the first half of February.
Overall, we expect multiple vaccines will be required to bring the pandemic to an end. With different vaccines proving useful in addressing emerging strains of the virus, providing equitable access to lower-income countries and ameliorating the current supply shortages.