Human trials of Oxford’s vaccine are still on hold in the US over safety concerns, two weeks after they were first paused.
AstraZeneca, the drug giant which owns the rights to the experimental jab, stopped global trials on September 8 because a British volunteer was hospitalised.
Leaked documents claimed the patient, a 37-year-old woman, developed ‘transverse myelitis’ — inflammation around the spinal cord, typically triggered by viruses but a potential side effect of other vaccines.
Doctors restarted trials in the UK five days later on September 12 after it was deemed safe to do so by an independent safety review committee and the UK regulator, the Medicines and Healthcare Products Regulatory Agency. They have also continued in Brazil, India and South Africa.
But regulators in the US have yet to resume the experiments over the incident, and are understood to be ‘highly concerned’ the jab may cause adverse reactions.
The FDA and the National Institutes of Health (NIH) are seeking to determine what caused the reaction, such as whether it was the vaccine, an underlying medical condition or another unknown factor.
It comes after President Donald Trump accused the FDA — with no evidence — of trying to delay a coronavirus vaccine until after the election for political purposes.
Trump reportedly wants to bypass normal US regulatory standards to fast-track Oxford’s vaccine for use in America by October — ahead of the presidential election in November.
Dr Anthony Fauci, director of the NIH, last week claimed that it is ‘just a matter of time’ before the trial resumes in the US, offering hope the vaccine will be back on track to become one of the first approved.
Uncertainty remains about what happened to the unnamed woman, who received the first dose of the experimental vaccine in June and the second in August.
AstraZeneca has repeatedly refused to confirm the diagnosis of transverse myelitis. It also insists there is no proof that the vaccine was to blame for the woman’s symptoms, which are believed to have now subsided.
Doctors restarted trials of Oxford’s vaccine in the UK on Saturday, September 12. They have also continued in Brazil, India and South Africa. But regulators in the US have yet to resume the experiments over the incident amid reports they are ‘highly concerned’ the jab may cause adverse reactions. Pictured: AstraZeneca facility in Waltham, Massachusetts
AstraZeneca, the drug giant which owns the rights to the experimental jab, stopped global trials on September 8 because a British volunteer was hospitalised. Pictured: A volunteer gets a jab in South Africa
Dr Anthony Fauci, director of the NIH, told CNN Tuesday that it is ‘just a matter of time’ before the trial resumes in the US
It’s the second time the trial has been paused. The first time, in July, was not publicly revealed until recently.
The trial was restarted after it was determined the volunteer had an ‘undiagnosed case of multiple sclerosis’, a condition that can cause the same neurological reaction as transverse myelitis, which was deemed to be unrelated to the vaccine.
AstraZeneca did not explain how that conclusion was reached – or why it waited more than a month to mention it publicly – and the details of the MHRA’s decision to restart trials again have not been revealed.
A statement said: ‘AstraZeneca and the University of Oxford, as the trial sponsor, cannot disclose further medical information.’
WHAT HAPPENED TO THE BRITISH VOLUNTEER?
There have been several reports about the woman’s state of health since AstraZeneca first announced trials were being paused on September 8.
The drug giant announced studies in the UK, US, South Africa and Brazil had been paused indefinitely while it investigated whether the patient’s illness was connected to the vaccine.
No details about the patient suffering the potential side-effect, or the nature of the reaction, were given in the initial statement, which said: ‘In large trials illnesses will happen by chance but must be independently reviewed to check this carefully.’
Medical news site Stat first reported the pause in the study, while The New York Times quoted a source saying a trial volunteer had transverse myelitis.
Amid rife suspicion, on September 9, Stat News reported AstraZeneca’s CEO, Pascal Soriot, told investors in a conference call that the trial was stopped because the woman had symptoms consistent with transverse myelitis.
Later that day, AstraZeneca said the media reports were ‘incorrect’, and that Mr Soriot had ‘stated that there is no final diagnosis and that there will not be one until more tests are carried out’.
A leaked AstraZeneca report seen by CNN gave details about the 37-year-old woman. The document, which is labelled an ‘initial report’, was sent to doctors running the clinical trials to warn them of the hospitalised British patient.
It described how the study participant ‘had trouble walking, weakness and pain in her arms, and other symptoms’.
Fourteen days after receiving her second dose of the vaccine in late August, the woman ‘experienced confirmed transverse myelitis’, the report allegedly says.
On September 2, while running, the study participant ‘had a trip (not fall) with a jolt.’ The report notes that she did not have any obvious injury to her cervical spine.
The next day, the woman had symptoms including difficulty walking, pain and weakness in her arms, pain and reduced sensation in her torso, a headache and reduced ability to use her hands.
She was hospitalised on September 5, several days prior to the SUSAR sent to doctors, and medical news website Stat said she was due to be discharged on September 9 – a discharge date was never officially confirmed.
The AstraZeneca report mentions twice that the woman was diagnosed with ‘confirmed’ transverse myelitis – which is in contrast to the company’s claims last week that the condition was yet to be confirmed.
The cover sheet on the report, allegedly sent by a contractor hired by AstraZeneca, also described her illness as ‘confirmed’ transverse myelitis.
A neurologist who saw the woman said her case ‘suggested the symptoms were consistent with the diagnosis of transverse myelitis’ and that she had no past history of neurological symptoms or significant illnesses.
But at another point, the report claimed to highlight there was ‘limited information concerning the subject’s relevant medical history.’
The neurologist said the woman’s symptoms started to get better quite rapid ‘considering her illness started only four days ago’.
‘Her symptoms were improving. Her strength and dexterity in her hands was getting better,’ the report said.
Physicians diagnose transverse myelitis by performing a thorough neurological examination. They use tests, such as an MRI and lumbar puncture, to rule out any other problems, such as an injury.
In response to the article in CNN, AstraZeneca said it contained ‘inaccuracies including the diagnosis, which is based on preliminary findings’. But it refused to reveal what they were.
British academics have been confident the decision was the right one.
Peter Openshaw, a professor of experimental medicine, Imperial College London, said: ‘It was right to suspend the trial to allow investigation. The restarting of the trial shows that the event was judged not to be vaccine related.
‘This is excellent news because the Oxford vaccine is one of the most promising. Inevitably with such a large trial there will be times when safety issues arise.’
But US experts have not been as supportive, calling for further details on the MHRA’s decision.
Dr Paul Offit, a professor at the University of Pennsylvania and a member of the FDA’s advisory committee on vaccines, told the New York Times it was unclear how AstraZeneca – or the UK regulators – determined the woman’s case of transverse myelitis was not related to the vaccine.
Mark Slifka, a vaccine expert at Oregon Health and Science University, said: ‘If there are two cases, then this starts to look like a dangerous pattern. If a third case of neurological disease pops up in the vaccine group, then this vaccine may be done.’
Dr Peter Jay Hotez, a virologist with Baylor College of Medicine in Houston, Texas, criticised statements released by UK regulators, who he said had failed to supply a clear rationale for resuming their trials.
‘Tell us why you came to that decision,’ he was reported as saying.
Dr Hotez also told the New York Times: ‘The communication around it has been horrible and unacceptable. This is not how the American people should be hearing about this.’
Professor Scott Lucas, of the department of political science and international studies at University of Birmingham, said it’s likely the US have not picked things back up due to lack of communication.
He told MailOnline: ‘I don’t think that it’s necessarily the US is stricter than the UK. I think both have fairly rigorous regulatory systems. I think it is a question of communication and of what happened to US officials, so the US has moved more slowly.’
The US Food and Drug Administration (FDA), the main drug regulator and American equivalent of the MHRA, has not commented but is reported to be requesting further data on the two adverse reactions from AstraZeneca, The Telegraph reported.
It will come as a blow to President Trump, who has previously slammed the FDA for ‘making it very difficult for drug companies to get people in order to test the vaccines and therapeutics’.
He wrote in a Tweet: ‘Obviously, they are hoping to delay the answer until after November 3rd. Must focus on speed, and saving lives!’
Trump reportedly wants to give Oxford and AstraZeneca’s vaccine emergency use authorisation, allowing it to be rolled out in the US without meeting full regulatory approval, before the election, according to the Financial Times which cited unnamed sources.
A representative for the Department of Health and Human Services said suggestions that the FDA would do this are ‘absolutely false’.
Professor Lucas said there was a ‘danger’ of falling into the ‘trap set by Trump’ – which is to believe any issues of safety and efficacy have been triggered to stop him winning the election.
‘The safety and efficacy process is to protect us,’ he said.
‘The more that politics tries to exploit our fear and concern, it could undermine the effort against Covid-19 because it could scupper vaccine trials.’
‘Trump’s only motive here is to get re-elected and to get a vaccine shown as effective before November 3. If it ended up killing a lot of people after November 3, it’s irresponsible and you’ve scared people to think any vaccine will cause that effect.
‘Certain politicians have tried to push aside the scientific advice, and once you do that, it has very serious effects. Yes, this trial has had two adverse cases and that must be seriously considered. There must be communication, but that is to safeguard the scientific process and it must not manipulated by politics.’
A ‘participant information sheet’ on Oxford’s website, updated on September 11, gave further clues into the situation.
It said: ‘In the current trial we have undertaken safety reviews when volunteers in the trials of ChAdOx1 nCoV-19 developed unexplained neurological symptoms including changed sensation or limb weakness, and have paused the study while a safety review took place.
‘After independent review, these illnesses were either considered unlikely to be associated with the vaccine or there was insufficient evidence to say for certain that the illnesses were or were not related to the vaccine.’
It did not mention transverse myelitis despite the reports of diagnosis. However, it did say Guillain-Barré syndrome could occur.
Guillain-Barré syndrome and transverse myelitis are closely related conditions, both causing inflammation of the spinal cord.
It said: ‘Reactions in the nervous system are also extremely rare, but can include an illness called Guillain-Barré syndrome, a condition in which people can develop severe weakness and can be fatal.’
Concerns around neurological side-effects are especially sensitive in the US after an emergency influenza vaccine in 1976 caused 450 cases of Guillain-Barré syndrome – a rare neurological disorder which has also been linked to the Zika vaccine.
Dr Avindra Nath, clinical director of the National Institute of Neurological Disorders and Stroke at the NIH, told Kaiser Health News: ‘The highest levels of NIH are very concerned.
‘Everyone’s hopes are on a vaccine, and if you have a major complication the whole thing could get derailed.’
Regulators want to test tissue or blood samples from the British patient and compare them to samples from other volunteers, Kaiser Health News reported.
This will be to see if they generated any antibodies from the immunization that also attack the brain or spinal cord tissue.
If scientists ascertain the vaccine caused the volunteer to suffer transverse myelitis, the arm may be permanently paused.
Dr William Schaffner, a professor of preventive medicine and infectious diseases at the Vanderbilt University Medical Center in Nashville, told DailyMail.com that it’s unclear whether the experimental vaccine or the placebo caused this side effect, but the longer the investigation, the more suspicion builds.
It comes after President Donald Trump accused the FDA — with no evidence — of trying to delay a coronavirus vaccine until after the election for political purposes
‘I would have thought if this patient received the placebo, this would have been a really brief assessment: ‘Oh well, this is a placebo. Can’t have anything to do with the vaccine. Open the trial again,” he said.
‘But the longer this goes on, the longer the suspicion that the patient had received the vaccine becomes more evident because this is exactly the kind of aberrant immune response that would be a concern for any vaccine, and this one in particular.’
However, Dr Anthony Fauci, director of the National Institutes of Health (NIH), which is conducting an investigation into the trial pause, said it was ‘just a matter of time’ before the US arm continues.
He added that he considered the participant’s illness a ‘one-off’ at this point, and that ‘it would be unusual to completely stop a trial on the basis of one single adverse event’.
‘You have to be extra special careful and watch out to see if it happens again, and then if it does, it becomes an entirely different situation,’ he told CNN last Tuesday.
In a tweet last week, Dr Eric Topol asked pharmaceutical companies running coronavirus vaccine clinical trials to be more open about their work.
‘The [Covid-19] vaccine companies haven’t been transparent; the stakes are big,’ wrote Topol, executive vice president of Scripps Research in California.
On Saturday, following calls for greater transparency and questions were raised about safety, AstraZeneca released a 111-page trial blueprint which gave closer details about its trial protocols and how it will calculate if the vaccine works.
It says that the goal is to develop a vaccine with 50 per cent effectiveness, as mandated by the FDA.
When the vaccine will be found 50 per cent effective, it will apply to the government for early release of the vaccine for emergency use.
There will have to be 150 people ill with confirmed coronavirus among participants who were vaccinated or received placebo shots.
The larger number of people who get sick with the virus, the stronger the data is to say whether or not people with the vaccine were prevented from caching it.
But a safety board will perform an early analysis after there have been just 75 cases, perhaps giving it enough data to apply for an early emergency use licence.