Trials of Oxford University’s coronavirus vaccine could be allowed to restart just days after a British volunteer was rushed to hospital with suspected swelling in their spinal cord.
UK drug giant AstraZeneca, which owns the rights to the vaccine, announced that all studies of the jab had been paused indefinitely while it investigates whether the patient’s side-effect is connected to the vaccine.
It is understood the female volunteer showed symptoms of transverse myelitis (TM), a rare inflammatory condition that affects the spinal cord.
This means no one else will be given the vaccine until the investigation has been completed.
However, health industry website Stat reported that a woman was suspected to have TM but the diagnosis was not confirmed, and she was on course to be discharged from hospital as early as last night.
Astrazeneca boss Pascal Soriot said the stop on trials was a ‘temporary pause’ and said that an independent committee of experts would investigate.
Trials of Oxford University’s coronavirus vaccine could be allowed to restart within days after a British volunteer was rushed to hospital with suspected swelling in their spinal cord. Pictured: Jacob Serrano, 23, who lost seven relatives to Covid-19, was the first American to take part in the trial
‘This is a routine action which has to happen whenever there is a potentially unexplained illness in one of the trials . . . in large clinical trials, illnesses will happen by chance and must be independently reviewed,’ a spokesman told The Times.
TM can be caused by viral infections, leading to pain, muscle weakness and numbness.
Ian Jones, professor of virology at the University of Reading, said: ‘It’s inflammation of nervous tissue which can be caused by a number of agents, one of which is viruses.
‘The stoppage might be because the symptoms are plausibly linked to the vaccine, although it could be something else.’
Trials for AstraZeneca’s shot are underway in the US, UK, Australia, Brazil (pictured) and other nations. Phase 3 testing will now be paused while safety data is reviewed
The condition is treatable with steroids, and patients usually recover from TM within weeks of first symptoms.
The development is a worrying blow to worldwide hopes for a jab being ready by Christmas because the Oxford vaccine was considered by many – including the World Health Organization – to be the frontrunner.
Health Secretary Matt Hancock said the pause to the Oxford vaccine trial is not necessarily a setback and that trials of the jab were put on hold over summer when a patient fell ill.
He told Sky News: ‘It is obviously a challenge to this particular vaccine. It’s not actually the first time it has happened to the Oxford vaccine and it’s a standard process in clinical trials.’
Asked if it will push back the roll-out of the vaccine, Mr Hancock said: ‘Not necessarily – it depends on what they find when they do the investigation. There was a pause earlier in the summer and that was resolved without a problem.’
AstraZeneca’s candidate vaccine, known as AZD1222, is in phase 3 trials – the final stage before safety and efficacy data can be submitted to regulators. Pictured: A Brazilian volunteer receiving the Oxford vaccine, July 24
Professor Terry Nolan from the University of Melbourne, said it was entirely plausible the volunteer had suffered transverse myelitis (TM) as a direct result of the vaccine.
The exact cause of TM is unknown, but it has been reported to occur after infections and vaccinations.
WHAT IS TRANSVERSE MYELITIS? HOW DISORDER CAUSES INFLAMMATION OF THE SPINAL CORD AND CAN LEAD TO PARALYSIS
The term myelitis refers to inflammation of the spinal cord, transverse refers to the pattern of changes in sensation.
Transverse myelitis is the broad name of the disease, and there are various sub-types.
Causes of the condition include infections, sometimes caused by bacteria in raw foods, immune system disorders, and other disorders that may damage or destroy myelin, the fatty white insulating substance that covers nerve cell fibers.
Inflammation within the spinal cord interrupts communications between nerve fibers in the spinal cord and the rest of the body, affecting sensation and nerve signaling below the injury.
That can lead to paralysis.
Condition can affect people of any age, gender, or race. It does not appear to be genetic or run in families.
Some people recover from transverse myelitis with minor or no long-term problems, but most suffer permanent impairments that affect their ability to perform ordinary tasks of daily living.
There is no cure for the disease.
Medical news site Stat first reported the pause in the study and said the possible side-effect occurred in a testing volunteer in Britain, who was expected to recover.
The vaccine, developed by Oxford University, is being tested in thousands of people in Britain and the US, and in smaller study groups in Brazil and South America.
Jacob Serrano, 23, who lost seven relatives to Covid-19, was the first American to take part in the trial.
He said: ‘I’d rather have us one step closer, no matter what it takes.’
An AstraZeneca spokeswoman said the pause is part of a standard review process which occurs in trial if there is a ‘potentially unexplained illness’ reported in any trial subject, and that the subject’s illness could also be coincidental.
‘As part of the ongoing randomised, controlled global trials of the Oxford coronavirus vaccine, our standard review process was triggered and we voluntarily paused vaccination to allow review of safety data by an independent committee,’ the spokeswoman said in a statement.
‘This is a routine action which has to happen whenever there is a potentially unexplained illness in one of the trials, while it is investigated, ensuring we maintain the integrity of the trials.
‘In large trials illnesses will happen by chance but must be independently reviewed to check this carefully.
‘We are working to expedite the review of the single event to minimise any potential impact on the trial timeline. We are committed to the safety of our participants and the highest standards of conduct in our trials.’
No details about the patient suffering the potential side-effect, or the nature of the reaction, were given.
Temporary holds of large medical studies are not uncommon, and looking into any unexpected reactions is a mandatory part of safety testing. It was not immediately clear how long AstraZeneca’s pause would last.
Two other vaccines are in huge, final-stage tests in the United States, one made by Moderna Inc and the other by Pfizer and Germany’s BioNTech.
Stats reported a total of nine vaccine candidates in late stage, or phase 3, trials, with AstraZeneca’s the first trial known to have been put on hold.
Despite some figures, such as US President Donald Trump, insisting a vaccine will be ready in a matter of months, Oxford University has said a vaccine might not be ready before 2022.
The university stressed that clinical trials have to be conducted with the utmost care.
‘It takes time to develop safe and effective vaccines – usually five to 10 years on average. Despite promising reports about potential coronavirus vaccines being developed worldwide, it could still take an estimated 12-18 months to develop one,’ a document on the university’s website, dated August 25, reads.
WHICH COUNTRIES HAVE ORDERED OXFORD’S VACCINE ALREADY?
The UK is the host of research and development efforts of the vaccine, which has been developed by researchers in Oxford and will be manufactured by AstraZeneca, a company based in Cambridge.
The British Government has ordered 100million doses of the jab and has already started manufacturing them so they’re ready to go if and when clinical trials are successful. The price paid has not been disclosed.
The US Government has ordered 100million doses of the vaccine and contributed $1.2billion (£910m) to the research and development of the jab.
European Union (EU)
The European Commission has agreed a deal for 300million doses of the vaccine if its clinical trials work, with the option to buy a further 100million. The deal has been made on behalf of countries in the EU. The amount of money spent is unknown.
Australia has confirmed it ordered enough doses of the vaccine to give one to its entire population of 25million people. It is not clear how many doses the nation has ordered. The UK – with a population of 66m but an order of 100m – ordered more than it needs.
One company in China has agreed a deal with AstraZeneca to make at least 100million doses of the vaccine.
Shenzhen Kangtai Biological Products, based in the city of Shenzhen, will increase capacity to 200m per year by the end of 2021.
A Russian company, R-Pharm, also has a deal to produce and distribute the vaccine, but it is unclear how many it will make or what it will pay to AstraZeneca.
Brazilian officials have set aside $360million (£274m) for at least 100million doses of the vaccine. Brazil is currently in one of the worst Covid-19 crises in the world with more than 3.6million official cases so far and 114,000 deaths.
‘It is essential that clinical trials are conducted with great care to ensure the safety of the participants and to fully establish the safety profile of the new products.
‘Safety is overseen closely during the trials both by the national regulator with a requirement of safety reporting placed on investigators throughout the trial, and inspections of the trial processes and procedures by the regulator, and an independent safety monitoring committee who reviews safety actively during the conduct of the clinical trial.
‘When an application for use of the vaccine is made to a regulator, they will fully assess the safety and efficacy data from the trials and use that to inform on their decision about potential use.’
Development of the AstraZeneca vaccine and eight others in phase 3 trials is being closely watched in the hopes they can stem the coronavirus pandemic that has killed more than 894,000 people worldwide, including nearly 190,000 Americans, and cost tens of millions their jobs.
It comes after vaccine developers – including AstraZeneca – pledged not to cut corners on safety and efficacy testing, despite US President Trump’s urgent push for the Food and Drug Administration (FDA) to give emergency approval to a vaccine ahead of the November 3 election.
‘As part of the ongoing randomised, controlled global trials of the Oxford coronavirus vaccine, our standard review process was triggered and we voluntarily paused vaccination to allow review of safety data by an independent committee,’ an AstraZeneca spokesperson told DailyMail.com.
‘This is a routine action which has to happen whenever there is a potentially unexplained illness in one of the trials, while it is investigated, ensuring we maintain the integrity of the trials.
‘In large trials, illnesses will happen by chance but must be independently reviewed to check this carefully. We are working to expedite the review of the single event to minimise any potential impact on the trial timeline. We are committed to the safety of our participants and the highest standards of conduct in our trials.’
AstraZeneca’s candidate vaccine, known as AZD1222, is in phase 3 trials – the final stage before safety and efficacy data can be submitted to regulators for approval – at dozens of sites across the US, and around the world.
Along with Pfizer, and Moderna, AstraZeneca and its partner Oxford University had hoped to know whether the shot worked and was safe by year-end.
Mr Hancock said on Monday the UK’s ‘best-case scenario’ was to get the vaccine to the most-vulnerable patients within months, a timeframe that now appears less likely to be met.
‘We have got 30 million doses already contracted with AstraZeneca,’ he said on UK radio station LBC.
‘In fact they are starting to manufacture those doses already, ahead of approval, so that should approval come through – and it’s still not certain but it is looking up – should that approval come through then we are ready to roll out.
‘The best-case scenario is that happens this year. I think more likely is the early part of next year – in the first few months of next year is the most likely.
‘But we’ve also bought vaccine ahead of it getting approved from a whole different series of international vaccines as well.’
More than 50,000 people worldwide had been taking part in ‘phase 3’ studies to see whether the Oxford jab can actually prevent people getting infected with Covid-19.
In these tests the vaccine is being given to tens of thousands of people in real-world environments to see if it stops them from catching Covid-19 in the community.
While trial holds to review safety data are not necessarily damning, the pause on AstraZeneca’s trial may very well delay the highly-anticipated results and completion of one of the fastest vaccine development pipelines in human history.
The jab was expected at the end of 2020 but its creators have had to temper expectations after community transmission began to fizzle out in Britain and stall crucial trials needed to seal its approval. It was called ChAdOx1 nCoV-19 before Oxford teamed up with AstraZeneca to manufacture it
Shares for AstraZeneca plummeted by eight percent in after-hours trading
Market confidence in the pharmaceutical giant took a hit as soon as reports of the trial hold emerged.
Shares for AstraZeneca plummeted by eight percent in after-hours trading.
President Donald Trump has hinted that he thinks a vaccine could be ready before a ‘special date’ – likely the November 3 election
The company is in now in mitigation mode to try to stay as close to its trial completion date as possible.
AstraZeneca is ‘working to expedite the review of the single event to minimize any potential impact on the trial timeline,’ the spokesperson told Stat News.
Disconcerting though any signs that could suggest potential flaws in a leading vaccine for the disease that’s killed nearly 190,000 Americans is, the move to pause a trial over safety concerns may be reassuring to some.
Hours before the trial was temporarily halted, AstraZeneca and eight other companies working on COVID-19 vaccines signed a pledge to prioritize safety of their shots over speedy development.
They promised to ‘uphold the integrity of the scientific process as they work towards potential global regulatory filings and approvals of the first COVID-19 vaccine.’
The pledge was made in response to growing concerns that governments would press firms and research institutions to rush a vaccine through trials and approval processes in an effort to bolster political capital and restore normalcy amid the pandemic.
Last week, the US Centers for Disease Control and Prevention (CDC) sent instructions to state health departments to prepare for the potential arrival of one of two coronavirus vaccines by the end of October.
Subsequently, President Trump hinted at the hopeful possibility that a vaccine could be ready before a ‘special date,’ prompting speculation that he was referring to the November 3 presidential election – just days after the end-of-October potential finish line in the CDC guidance.
Health officials like infectious disease expert Dr Anthony Fauci, US Surgeon General Dr Jerome Adams and Trump’s own vaccine czar Dr Moncef Slaoui were all quick to assure the American public that it was possible, but unlikely, that a shot would be ready by then, and that the FDA would pay no mind to the date, but only the data, to determine when a vaccine is ready for distribution.
Pfizer, however, confirmed that it hoped to have sufficient trial data to know whether its shot was safe and effective by late October, and would submit for FDA approval ‘immediately’ afterwards.
Most experts and observers speculate that the two unnamed shots referenced in the CDC guidance were Moderna’s and Pfizer’s, not AstraZeneca.
The trial hold casts even further doubt over the possibility that the firm’s vaccine will be the first ready for the US market.
Operation Warp Speed, the Trump administration’s effort to speed vaccine development, primarily by contributing funding to private companies working on shots, announced that AstraZeneca would be awarded up to $1.2 billion in funding for its vaccine development in May.
The US has inked a deal with AstraZeneca for 300 million doses of its shot – if the vaccine is greenlit as safe and effective by the FDA – and had set its sights on an approval date as early as October, which seems increasingly improbable.
WHICH VACCINES HAVE THE UK SECURED DEALS FOR?
1. GlaxoSmithKline and Sanofi Pasteur: 60million doses
The Government revealed on July 29 it had signed a deal with pharmaceutical giants GlaxoSmithKline (GSK) and Sanofi Pasteur
If the vaccine proves successful, the UK could begin to vaccinate priority groups, such as frontline health and social care workers and those at increased risk from coronavirus, as early as the first half of next year, the Department for Business, Energy & Industrial Strategy (BEIS) said.
Human clinical studies of the vaccine will begin in September followed by a phase 3 study in December.
The vaccine is based on the existing technology used to produce Sanofi’s seasonal flu vaccine. Genetic material from the surface protein of the SARS-CoV-2 virus is inserted into insect cells – the basis of Sanofi’s influenza product – and then injected to provoke an immune response in a human patient.
2. AstraZeneca (manufacturing University of Oxford’s): 100million
AstraZeneca, which is working in partnership with Oxford University, is already manufacturing the experimental vaccine after a deal was struck on May 17.
Professor Sarah Gilbert, who is leading the Oxford team, is confident the jab could be ready for the most vulnerable people by the end of the year.
Her comments came after the results from the first phase, published in The Lancet on July 20, showed promise.
The team have genetically engineered a virus to look like the coronavirus – to have the same spike proteins on the outside – but be unable to cause any infection inside a person. This virus, weakened by genetic engineering, is a type of virus called an adenovirus, the same as those which cause common colds, that has been taken from chimpanzees.
3. BioNTech/Pfizer: 30million
US drug giant Pfizer – most famous for making Viagra – and German firm BioNTech were revealed to have secured a deal with the UK Government on July 20.
It reported positive results from the ongoing phase 2/3 clinical trial of one called BNT162b1 on July 1. The company is still running phase 2 trials at the moment.
Pfizer’s vaccine is one called an mRNA vaccine, which do not directly inject bits of the virus into the body but send genetic material.
mRNA vaccines programme the body to produce parts of the virus itself by injecting the body with a molecule that tells disease-fighting cells what to build. The immune system then learns how to fight it.
4. Valneva: 60million
The Government has given Valneva — whose vaccine is understood to be in the preclinical stages of development — an undisclosed amount of money to expand its factory in Livingston, Scotland.
While the Government revealed a 60million dose deal on July 20, the company said it had reached agreement in principle with the UK government to provide up to 100million doses.
Valneva’s jab is an inactivated whole virus vaccine, meaning it injects a damaged version of the coronavirus itself into the body.
The virus has been destroyed in a way that makes it unable to cause infection, but the body still recognises it as a dangerous intruder and therefore mounts an immune response which it can remember in case of a real Covid-19 infection.
5. Janssen (Johnson & Johnson): 30million
The Government has agreed to buy 30million doses of a vaccine made by Janssen if it works.
Officials have agreed to help the company in its development of the jab by part-funding a global clinical trial. The first in-human trials of Janssen’s jab began in mid-July and are being done on adults over the age of 18 in the US and Belgium.
The jab is named Ad26.COV2-S, recombinant, and is a type of jab called a viral vector recombinant vaccine.
Proteins that appear on the outside of the coronavirus are reproduced in a lab and then injected into the body to stimulate an immune reaction.
The ‘Ad’ part of the vaccine’s name means it works using an adenovirus – a virus best known for causing the common cold – as a vehicle to transport the coronavirus genetics into the body.
6. Novavax: 60million
Britain has ordered 60million doses of a vaccine being developed by the US-based company Novavax. It will help to fund late-stage clinical trials in the UK and also boost plans to manufacture the vaccine in Britain.
Novavax’s jab, named NVX-CoV2373, showed positive results in early clinical trials.
It produced an immune response in 100 per cent of people who received it, the company said, and was safe and ‘generally well-tolerated’.
Novavax’s candidate is also a recombinant vaccine and transports the spike proteins found on the outside of the coronavirus into the body in order to provoke the immune system.
7. Imperial College London: Unknown quantity
Imperial College London scientists are working on Britain’s second home-grown hope for a jab. The candidate is slightly behind Oxford’s vaccine in terms of its progress through clinical trials, but is still a major player.
The UK Government is understood to have agreed to buy the vaccine if it works but details of a deal have not yet been publicised.
Imperial’s jab is currently in second-phase human trials after early tests showed it appeared to be safe.
Imperial College London will try to deliver genetic material (RNA) from the coronavirus which programs cells inside the patient’s body to recreate the spike proteins. It will transport the RNA inside liquid droplets injected into the bloodstream.