Regeneron will stop placebo enrolment into a phase 3 study of its COVID-19 antibody cocktail REGEN-COV after the Independent Data Monitoring Committee (IDMC) found the treatment has ‘clear efficacy’.

The phase 3 trial is assessing the investigational treatment, which combines casirivimab with imdevimab, in outpatients with COVID-19.

In this trial, the IDMC found clear clinical efficacy on reducing the rate of hospitalisation and death with both doses of REGEN-COV (1,200mg and 2,400mg) tested in the study compared to placebo.

Following this, the IDMC has recommended halting enrolment into the placebo group, which Regeneron said it will do ‘immediately’.

From now on, the study will continue to enrol patients into both the 1,200mg and 2,400mg REGEN-COV treatment groups.

In a statement, Regeneron said that it had not yet had any access to the unblinded data that prompted the IDMC’s recommendation, including the relative treatment benefit of either REGEN-COV doses tested.

It added that it will share detailed results from the study when they are available in March 2021.

In January 2021, Regeneron announced that the antibody cocktail can be used as a passive vaccine to prevent COVID-19 in people who are at high risk of infection.

The first exploratory analysis of 400 evaluable high-risk participants in the phase 3 prevention trial found that passive vaccination with REGEN-COV resulted in 100% prevention of symptomatic COVID-19 infections.

On top of that, the cocktail led to approximately 50% lower overall rates of infection – with infections occurring with REGEN-COV therapy all being asymptomatic.

Johnson & Johnson’s (J&J) one-dose COVID-19 vaccine has received an emergency use authorisation (EUA) from the US Food and Drug Administration (FDA).

The authorisation quickly followed a positive meeting of the FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC), which unanimously backed an EUA for the jab.

Briefing documents published ahead of the VRBPAC meeting endorsed the safety and efficacy of J&J’s vaccine and reiterated its efficacy of 66.1% in a phase 3 trial.

The EUA was supported by data from the phase 3 ENSEMBLE trial, within which J&J’s vaccine demonstrated 85% efficacy against severe COVID-19 across all regions studied.

The study was conducted in eight countries across three continents, with 44% of participants enrolled in the US, 41% in Central and South America and 15% in South Africa.

Across all participants from the different geographies, the vaccine was 66.1% effective overall in preventing moderate-to-severe COVID-19, 28 days after vaccination.

In the US, the efficacy rate increased slightly to 72%, while in Latin America and South Africa the vaccine was 66% and 57% effective, respectively.

In South Africa, J&J said that 95% of the COVID-19 cases observed in the study were caused by the newly discovered B.1.351 virus variant.

In a statement, J&J said that it is expecting to deliver 100 million one-dose vaccines to the US during the first half of 2021.

A major real-world study including around 1.2 million people has found the Pfizer/BioNTech vaccine to be 94% effective following the second dose.

The research, conducted in Israel, used data from Clalit Health Services to evaluate the effectiveness of the Pfizer/BioNTech vaccine, also known as BNT162b2.

The study matched all individuals who were newly vaccinated during the period running from 20 December 2020 to 1 February 2021 to unvaccinated controls in a 1:1 ratio.

It documented outcomes including infection with severe COVID-19, symptomatic COVID-19, COVID-19-related hospitalisation, severe illness and death.

The researchers measured vaccine effectiveness for the study outcomes at days 14 to 20 after the first dose of BNT162b2, and at seven or more days after the second dose.

They found that the Pfizer/BioNTech vaccine was 57% effective at preventing symptomatic COVID-19 after the first dose, which climbed to 94% following the second dose.

After the second dose, the vaccine was also 87% effective at preventing hospitalisation and 92% effective at preventing severe disease.

The study also estimated effectiveness for the prevention of death from COVID-19 to be 72% for days 14 through 20 after the first dose.

The findings for effectiveness in preventing symptomatic COVID-19 was also consistent across all age groups, although the researchers added there could potentially be slightly lower effectiveness for people with multiple coexisting conditions.

Moderna has announced plans for the development of booster jabs of its COVID-19 vaccine against new and emerging variants of the virus.

Moderna has unveiled its strategy for booster jabs to increase the effectiveness of its authorised vaccine, mRNA-1273, in a bid to address new ‘variants of concern’.

This includes the variant first discovered in South Africa, known as B.1.351, for which Moderna has developed a variant-specific vaccine candidate – mRNA-1273.351.

Moderna announced in February that it had completed manufacturing of clinical trial material for this modified vaccine candidate, and has sent doses of the jab to the US National Institute of Health (NIH) for phase 1 testing.

The company also said that it would develop additional booster doses as part of its strategy to address new and emerging variants.

This includes a multivalent booster candidate, mRNA-1273.211, that will combine Moderna’s authorised vaccine with the mRNA-1273.351 candidate in a single vaccine.
The company will also develop a third dose of mRNA-1273 as a booster at a dose level of 50µg.

Moderna is planning to evaluate mRNA-1273.351 and mRNA-1273.211 in participants who have not received a COVID-19 vaccine and in participants in clinical studies who have had the original mRNA-1273 vaccine.

A previous study of Moderna’s mRNA-1273 vaccine found a decrease in neutralising antibodies against the B.1.351 variant.

The researchers conducting this study noted that ‘protection against the B.1.351 variant conferred by the mRNA-1273 vaccine remains to be determined’.

The US Food and Drug Administration (FDA) has issued updated guidance for companies developing vaccines, tests and therapeutics to address COVID-19 variants.

The FDA agency said that if a variant emerges in the US that is ‘moderately’ or ‘fully’ resistant to existing vaccines, it may be necessary to modify the vaccines.

In this situation, the FDA said that it expects the manufacturing information to remain generally the same for both an authorised vaccine and a modified vaccine candidate developed by the same manufacturer.

The FDA guidance also recommends that clinical data for the effectiveness of modified vaccines should be supported by clinical immunogenicity studies.

Such studies would need to compare an individual’s response to the virus variants induced by the modified vaccine to the immune response induced by the original, authorised vaccine.

The FDA has also encouraged vaccine makers to study the modified vaccine in both non-vaccinated individuals and in people who have previously been vaccinated with the original, authorised jab.

In its guidance to COVID-19 test developers, the FDA recommended that companies consider the potential for future viral genetic mutations when designing a test, as well as conducting routine monitoring to evaluate the potential impact of new/emerging variants on the performance of molecular, antigen and serology COVID-19 tests.

Finally, for therapeutics – particularly monoclonal antibodies targeting the virus – the FDA has advised drug developers to continuously monitor genomic databases for emerging COVID-19 variants and evaluate specific variants in the product target that could potentially impact its activity.

The European Union (EU) has launched a new programme to investigate COVID-19 variants.

The European Commission’s (EC) president Ursula von der Leyen told French financial newspaper Les Echos that the programme will unite health authorities and laboratories in preparing for the next generation of vaccines that could be required against new variants.

The programme, ‘HERA Incubator’, has been described as a ‘European bio-defence preparedness plan’ against COVID-19 variants and will have its own funding. It will bring together researchers, biotech companies, manufacturers, regulators and public authorities to monitor variants, as well as exchange data and cooperate on adapting vaccines, according to the EC.

The plan will focus on the detection and analysis of virus variants, while enabling the speedy regulatory approval and mass production of adapted or novel COVID-19 vaccines.
  
The EC said it will support EU countries to carry out more testing and genome sequencing by developing specialised tests for new variants.

At least €75m in EU funding will be provided to ensure countries can undertake the above measures, and also prepare for adapting vaccines and vaccine production capacity.

The EC has also announced plans to speed up the procedures for approving adapted versions of existing vaccines, in the situation that new variants are less affected by current jabs.

The Commission said it would base the framework for approving adapted COVID-19 vaccines on the framework it currently uses for the annual flu vaccine.