Further setbacks in pursuit of COVID vaccine and ‘cure’

Matt Woodley

14/10/2020 3:13:10 PM

Two randomised controlled trials involving tens of thousands of people have been paused to investigate potential safety concerns.

Close up of vaccine vials
Johnson & Johnson said it is not yet clear whether the ill trial participant received its vaccine candidate or a placebo.

Both trials were put on hold to investigate unexpected adverse reactions during testing.
Eli Lilly, the US company conducting a late-stage testing of an experimental antibody treatment for COVID-19, announced its pause a day after pharmaceutical giant Johnson & Johnson (J&J) revealed it too had halted a phase 3 trial of its new COVID vaccine over potential safety concerns.
However, the double-blind nature of both trials means more work is needed to identify the potential issues.
Along with REGN-COV2 – a similar experimental antibody COVID treatment currently being tested – Eli Lilly’s combination therapy had been recently touted as a ‘cure’ by US President Donald Trump following promising early results.
But, in an emailed statement, Eli Lilly spokesperson Molly McCully confirmed the independent data safety monitoring board (DSMB) for the therapy’s ACTIV-3 trial had recommended a pause out of an ‘abundance of caution’.
‘[Eli] Lilly is supportive of the decision by the independent DSMB to cautiously ensure the safety of the patients participating in this study,’ she said in the statement.
The J&J trial is also being investigated by an independent DSMB. A company release said the number of serious adverse events can ‘reasonably’ be expected to increase in trials involving large numbers of participants.
‘Adverse events – illnesses, accidents, etc – even those that are serious, are an expected part of any clinical study, especially large studies,’ the release states.
‘We must respect this participant’s privacy. We’re also learning more about this participant’s illness, and it’s important to have all the facts before we share additional information.
‘Further, as many trials are placebo-controlled, it is not always immediately apparent whether a participant received a study treatment or a placebo.’
Commenting on the J&J pause, Pro-Vice Chancellor of Health Sciences at Murdoch University Professor Jeremy Nicholson said while each case has to be investigated thoroughly, it would be ‘worrying’ if it reported a neurological effect like that experienced by a participant in Oxford University and AstraZeneca’s high-profile AZD1222 candidate trial.

‘Vaccines can sometimes cause the same virus-related problems that they are meant to prevent,’ he said.
‘Worryingly, there are now multiple reports of neuropathological effects of COVID-19 of varying presentation and severity, so if it were to be a neuro side problem that would need special attention.’

However, Professor Nicholson adds it is ‘far too early’ to tell if there is a generic safety problem with respect to neurological, or other organ systems, effects of any of the new coronavirus vaccines.
‘That’s what the testing is for,’ he said. ‘This is the reason that vaccine trials take a long time, to establish the safety of the treatment when given at large scale.

‘There can be no rushed release of a drug, vaccine or antibody cocktail when the safety of millions of people is at stake – no matter what the political pressure.’
Like AZD1222 and other COVID-19 vaccine candidates, the J&J vaccine uses an adenovirus vector – a harmless virus that does not multiply in humans – to deliver the part of the SARS-CoV-2 virus protein that elicits antibodies.
Head of the Biosecurity Program at the Kirby Institute Professor Raina MacIntyre pointed out there are no existing licensed vaccines that have used such a method, and Australia should diversify its options to ensure it has enough to choose the best ones once they pass clinical trials.
‘If we focus only on one or two vaccines and they end up being non-starters or have serious side effects, we could be left out in the cold,’ she said.
‘It is best to choose several different vaccine technologies – MRNA-based, vectored, subunit etc – as each technology will have unique features and may also be associated with safety.’
Professor MacIntyre also warned that continued monitoring of vaccines after they have passed clinical trials and been licensed is vital, as adverse reactions are sometimes not identified during the testing phase.
‘This happened with the dengue vaccine, which showed no safety issue in clinical trials, but antibody-dependent enhancement occurred when it was used in a large-scale vaccination program in the Philippines, with far higher numbers of people vaccinated than in the clinical trials,’ she said.
‘The same occurred with the very first rotavirus vaccine – a very rare side effect, a bowel disorder in children, was not seen in the clinical trials, but became apparent when the US began vaccinating infants with it in the 1990s.
‘That vaccine was withdrawn and the subsequent, newer rotavirus vaccines had to undergo massive scale clinical trials [involving more than 60,000 people] to prove they did not cause that same problem.
‘So a clinical trial is not the end of the story.’
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