Leading researchers and bioethicists have signed a letter urging Pfizer to delay submitting a marketing authorisation application for its potential COVID-19 vaccine, reported Bloomberg.

The letter comes after reports that Pfizer and its partner BioNTech were expecting conclusive results from a study of their mRNA-based shot in October, raising concerns that the companies could seek regulatory approval before achieving convincing safety data.

The researchers urged Pfizer and BioNTech to delay filing the vaccine candidate with the US Food and Drug Administration (FDA) until after the companies had access to follow-up safety data.
They added that Pfizer’s clinical trial needs to monitor participants for at least another two months after they have received a second dose of the vaccine candidate, BNT162b2.

‘To be successful, the public needs to have the utmost trust in the vaccine and the science behind it,’ the letter said.

In early study results, Pfizer’s vaccine candidate elicited promising antibody levels against the SARS-CoV-2 virus, which causes COVID-19. BNT162b encodes an optimised SARS-CoV-2 full length spike glycoprotein and is also mRNA-based.

An mRNA vaccine tricks the body into producing some of the targeted viral proteins that, in turn, can be detected by the immune system, which begins to produce antibodies against them.
Pfizer is among a number of top companies that signed a pledge earlier this month promising to uphold rigorous safety and efficacy protocols during and after the clinical development of their respective candidates.

The pledge was also co-signed by the CEOs of AstraZeneca, Johnson & Johnson, Merck, Moderna and Novavax, as well as Sanofi and GlaxoSmithKline.

After the Medicines Health Regulatory Authority (MHRA) confirmed that it was safe to do so, clinical trials for the AstraZeneca/Oxford coronavirus vaccine, AZD1222, have resumed in the UK.

The pause was instituted after a patient in the UK suffered a reported side effect. Investigations were conducted to identify if the adverse reaction was linked to the vaccine.

No further medical information was disclosed by AstraZeneca or the University of Oxford, the trial sponsor, for confidentiality reasons.

However, it was reported in the New York Times that the side effect suffered by a participant in the UK trial was transverse myelitis, which can be caused by viral infections and affects the spinal cord.

The voluntary pause, placed across all global trials on 6 September, was triggered by the standard review process, which gives independent committees and international regulators time to review the safety data.

According to a release from AstraZeneca on 12 September: ‘The UK committee has concluded its investigations and recommended to the MHRA that trials in the UK are safe to resume.’

The release continued: ‘AstraZeneca is committed to the safety of trial participants and the highest standards of conduct in clinical trials. The Company will continue to work with health authorities across the world and be guided as to when other clinical trials can resume to provide the vaccine broadly, equitably and at no profit during this pandemic.’

The phase 3 trials involve some 30,000 participants in the US, as well as participants in the UK, Brazil and South Africa.

GlaxoSmithKline’s chief executive officer Emma Walmsley is ‘optimistic’ that a vaccine against COVID-19 will be widely available in 2021.

Speaking at the third annual Helen Alexander Memorial Lecture – an online event of the Confederation of British Industry (CBI) – Walmsley said she “share(s) the optimism that we will have solutions (for COVID-19) next year”.

“The challenge here is getting to the scale that is required. Lots of progress has also been made for therapeutics,” she added.

GSK is currently partnering with French pharma Sanofi on a COVID-19 vaccine project, where it is supplying an adjuvant to be used in combination with Sanofi’s recombinant protein-based vaccine candidate.

Adjuvants are particularly useful in a pandemic setting as they boost the efficacy of vaccine candidate, thereby reducing the amount needed per dose.

Vaccine developers have been moving at unprecedented speed in an effort to develop a successful vaccine targeting SARS-CoV-2, the novel coronavirus which causes COVID-19. However, this speed, while impressive given the current pandemic conditions, has raised concerns among experts, especially with regard to ensuring the safety of any potential COVID-19 vaccine.

Pfizer’s CEO Albert Bourla, along with GSK’s Walmsley, was among nine top pharma and biotech chiefs to sign a pledge promising to uphold rigorous safety and efficacy protocols for their respective vaccine candidates.

The leaders of AstraZeneca, Johnson & Johnson, Merck, Moderna, Novavax, BioNTech and Sanofi have also signed the pledge in an effort to mitigate some of the concerns around the safety and efficacy standards of their potential COVID-19 vaccines.

The EU will assume responsibility for claims over a certain amount made against AstraZeneca (AZ) relating to potential side effects from its Oxford University-partnered COVID-19 vaccine.

According to Reuters, AZ will only pay for legal costs up to a certain threshold, at which point the costs will be shouldered by European governments. It is uncertain exactly how the costs will be shared with individual European governments.

The EU liability agreement would cover legal costs and potential compensation in the rare case of serious side effects from AZ’s COVID-19 vaccine occurring.

Although it is unlikely that such an event will happen, the speed at which vaccines for the novel coronavirus – SARS-CoV-2 – are currently being developed increases the need for protection against unforeseen sideeffects.

AZ reached an agreement with the EU in August to provide 400 million doses of its vaccine candidate. The deal is to be financed with the EC’s ‘Emergency Support Instrument’, which has funds dedicated to the creation of a portfolio of potential vaccines produced by different companies.

The AZ/EU liability deal was negotiated before the Cambridge, UK-headquartered pharma company was forced to pause trials of its COVID-19 vaccine after a British participant developed neurological symptoms. Although the trials have resumed in Britain, they are still on hold in the US.

Results from a phase 1 study of Moderna’s COVID-19 vaccine candidate have shown promise in older adults, with the vaccine generating a strong immune response in this population.

The results from the study supported by the US National Institutes of Allergy and Infectious Diseases (NIAID) were published in the New England Journal of Medicine on 29 September.
The new data builds and expands on the initial results released n August detailing the efficacy of Moderna’s mRNA-1273 vaccine in 20 adults between the ages 56-71 and older.

The updated results come from an expansion of the trial which included a larger proportion of older adults, comprising 20 adults aged 56-70 years old and 20 adults aged 71 years and older.
Ten volunteers in each age group received a lower dose of the vaccine – 25 µg – and the other ten received a higher dose of 100 µg. Participants then received a second dose of the same vaccine at the same dosage a month later.

The researchers found that the mRNA-1273 vaccine was well-tolerated in this older age group, with participants exhibiting a good immune response following administration of two doses of the vaccine, and only some older volunteers experienced transient adverse events including fever and fatigue after vaccination.

“Given the increased morbidity and mortality of COVID-19 in older and elderly adults, this data gives us optimism in demonstrating mRNA-1273’s protection in this population, which is being evaluated in the phase 3 COVE study,” said Tal Zaks, chief medical officer of Moderna.

Healthy participants in the UK may be purposefully infected with the novel coronavirus in an effort to test the efficacy of possible COVID-19 vaccines.

The human ‘challenge trial’ programme would be the first of its kind to be carried out in the world, with volunteers set to be exposed to the virus and given a potential vaccine at the same time, and then closely monitored in quarantine for up to a month.

This would allow researchers to closely observe participants and gather samples while tracking the progress of the virus in real time, which would also allow for long-term follow-up.
Also, as infection is guaranteed in this type of trial, investigators would also be able to determine a vaccine’s efficacy at a faster rate than a standard phase 3 trial.

In traditional phase 3 vaccine testing, participants return to their normal day-to-day life after receiving a candidate vaccine. This usually means that only a small proportion of participants will encounter the virus, and it can take more volunteers and a longer period of time to reveal differences between the vaccine treatment and placebo groups.

According to the Financial Times, the government-funded studies could begin by January in London, with an announcement unveiling the trials set for next week.

It is hoped that the ‘challenge trials’ will be able to quickly determine how well late-stage COVID-19 vaccines work, as some of these candidates are set to complete phase 3 testing before the end of the year.

So far, 2,000 volunteers in the UK have signed up to the 1DaySooner movement, an organisation founded in April which has been petitioning for COVID-19 ‘challenge trial’ volunteers.