AstraZeneca is on the up after announcing that its Oxford University-partnered COVID-19 vaccine candidate has shown promise in both older and younger adults.

According to a report from the Financial Times (FT), the vaccine candidate – AZD1222 – triggers protective antibodies and T cell responses in older age groups. Since the beginning of the pandemic, older adults have been identified as having a higher risk of hospitalisation and death from COVID-19 compared to younger people.

According to the US Centers for Disease Control and prevention (CDC), it can also prove more challenging to find a vaccine that is effective for older adults.

This is because older adults have more risk factors associated with developing severe symptoms from infectious diseases, and also because the immune system undergoes immunosenescence as individuals age.

Immunosenescence is the gradual deterioration of the immune system, which occurs as a natural part of ageing. This makes it harder for vaccine developers to create a shot which prompts a similar immune response between young adults and older adults.
In addition to the promising immune response in older adults, AZ also said that adverse responses were lower among the elderly, according to Reuters.

“It is encouraging to see immunogenicity responses were similar between older and younger adults and that reactogenicity was lower in older adults, where the COVID-19 disease severity is higher,” an AZ spokesman also told Reuters.

The US Food and Drug Administration (FDA) has approved Gilead’s remdesivir – now Veklury – for the treatment of hospitalised COVID-19 patients.

The full approval makes remdesivir the first and only treatment approved for COVID-19 in the US, following its earlier, limited emergency use authorisation.

Gilead’s antiviral drug scored an emergency use authorisation in May for use in patients hospitalised with a SARS-CoV-2 infection – the virus which causes COVID-19.
In the phase 3 ACTT-1 trial of remdesivir, treatment with Gilead’s drug resulted in clinically meaningful improvements across multiple outcome assessments when compared to placebo.

In the final day 29 results, remdesivir plus standard-of-care treatment were able to cut the time to clinical recovery by five days compared to placebo, with a median time to recovery of ten days with remdesivir treatment compared to 15 days in the placebo group.
According to Gilead, this result was most potent in patients who required oxygen at baseline – in this subgroup, patients receiving remdesivir achieved clinical recovery seven days faster than those in the placebo group, with a median time to recovery of 11 days for remdesivir and 18 days for placebo.

Remdesivir has been touted as a potential treatment for COVID-19 since the early days of the pandemic, with the drug recently being administered to US president Donald Trump after he tested positive for the virus earlier in October.

The US Food and Drug Administration (FDA) will not require pre-approval inspections for vaccine developers seeking emergency use authorisations (EUA), Bloomberg reports.

Typically, companies who seek approval for a drug or a vaccine are required to undergo inspections prior to authorisation from the FDA.

Jerry Weir, director of viral products at the FDA’s vaccines office, revealed that companies who submit their COVID-19 vaccine for an EUA will not have to undergo such inspections during an FDA advisory committee meeting.

Weir did add that all companies submitting a potential COVID-19 vaccine for an EUA will be required to submit complete details of their manufacturing processes and demonstrate how they have established a quality control unit.

Moderna, one of the companies at the forefront of the race to find and submit a COVID-19 vaccine for approval, has never undergone an inspection by the FDA, according to Bloomberg.

However, Moderna has partnered with Lonza to bolster its capacity for manufacturing scale-up of its mRNA-based vaccine candidate, with the contract manufacturer’s site having been inspected by the FDA several times.

Eli Lilly, which is developing antibody drug treatments for potential use against COVID-19, was issued an Official Action Indicated (OAI) notice last year after an inspection at its Branchburg, New Jersey site in the US.

Reuters reported that the FDA inspectors had discovered ‘serious quality control issues’ at the plant, finding that data had been deleted from previous manufacturing processes.
The Branchburg site is among several worldwide Lilly plants currently producing bamlanivimab, one of the company’s COVID-19 neutralising antibodies.

AstraZeneca (AZ) and Johnson & Johnson (J&J) are both set to resume their respective phase 3 COVID-19 vaccine trials following separate trial pauses.

AZ paused its phase 3 trial of its Oxford University-partnered COVID-19 vaccine candidate, AZD1222, on 6 September after a participant in the UK-based trial experienced a serious adverse event.

Although the trial has already resumed in the UK, Brazil, South Africa and Japan, the US-arm remained on pause after the Food and Drug Administration (FDA) broadened its investigation into the event.

After reviewing all of the safety data from the global trials, the FDA authorised the restart of the US arm of the trial on Friday.

In a statement, AZ said that participant illness is not uncommon in large scale vaccine trials, adding that every case must be evaluated to ensure the safety of the assessment.
The company added that it is expecting results from the late-stage trials of AZD1222 later this year, although it said this is dependent on the rate of COVID-19 infection in the communities where the clinical trials are being conducted.

In a separate announcement, J&J said that the Independent Data Safety Monitoring Board (DSMB) overseeing the pause of its phase 3 ENSEMBLE study recommended resuming trial recruitment.

In October, J&J voluntarily paused the trial after a participant in the large-scale trial developed an unexplained illness.

However, based on the information gathered to date and the input of independent experts, J&J said that it has found no evidence that its vaccine candidate caused the event.
Following consultation with the FDA, J&J is now preparing to resume the US-based trial, including submissions for approval by the Institutional Review Boards.

Eli Lilly has cut short a clinical trial of its antibody treatment bamlanivimab in hospitalised COVID-19 patients after reviewing an updated data set.

Lilly released a statement saying that no additional COVID-19 patients in the hospitalised setting will receive bamlanivimab, based on trial data suggesting that the antibody is ‘unlikely’ to help this group of patients recover.

Lilly initially paused the US National Institute of Allergy and Infectious Diseases (NIAID) partnered study earlier this month.

According to Reuters, a US National Institutes of Health (NIH) spokeswoman said the trial in question was paused when the independent data and safety monitoring board (DSMB) found that the antibody-treated group showed a different ‘clinical status’ after five days of treatment compared to the placebo arm.

In a statement regarding the original trial pause, Lilly said that the participants in the ACTIV-3 study had been infected with the novel coronavirus for a longer period of time, meaning they could have more severe symptoms when compared to patients in other trials investigating bamlanivimab.

This could result in the neutralising antibody having less benefit in hospitalised COVID-19 patients, Lilly added.

The pharma giant is investigating bamlanivimab on its own and in combination with other antibodies and antivirals across a number of additional settings, which have remained unaffected.

This includes an ongoing phase 2 study in people recently diagnosed with COVID-19 in the ambulatory setting, a phase 3 study for the prevention of COVID-19 in residents and staff at care homes and in recently diagnosed mild-to-moderate COVID-19 patients.

Regeneron has announced that it has stopped enrolment of severely ill COVID-19 patients into its antibody cocktail treatment trials based on expert recommendations.

According to Regeneron, the independent data monitoring committee (IDMC) for the REGN-COV2 antibody cocktail COVID-19 treatment trials recommended that the current hospitalised patient study be modified.

In particular, the IDMC recommended halting further enrolment of patients requiring high-flow oxygen or mechanical ventilations after identifying potential ‘safety signals’ as well as an ‘unfavourable risk/benefit profile’.

Despite this enrolment pause, the IDMC also recommended continuing enrolment of hospitalised patients requiring no or low-flow oxygen, as the risk-benefit profile remains acceptable in this cohort.

The US Food and Drug Administration (FDA) is currently evaluating REGN-COV2 for a potential emergency use authorisation, although Regeneron has only submitted the antibody cocktail under this approval process for mild-to-moderate high-risk outpatients.
Following the IDMC recommendations, Regeneron has shared the updates with the FDA as well as the independent committee monitoring the RECOVERY trial in the UK, which is also evaluating REGN-COV2 in hospitalised patients.