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When veteran scientist Craig Rayner saw Australian laboratory results had been published that suggested the drug ivermectin could potentially fight COVID-19, he felt a sense of dread.
The experienced drug developer was aware experiments with ivermectin had been performed. Two weeks earlier, researchers at the Monash Biomedicine Discovery Institute had sought his opinion on some laboratory tests that showed the drug could stop the SARS-Cov-2 virus from growing in cell culture.
Sydney gastroenterologist Thomas Borody has patented an ivermectin therapy for COVID-19 patients.Credit:Wolter Peeters
The results were tantalising. Ivermectin is a commonly used and inexpensive antiparasitic to treat worms in animals and lice and scabies in humans. It was March 2020. The pandemic was in its ascendancy and there was no vaccine in sight.
But although Dr Rayner agreed at the time that the results were interesting, they were nowhere close to proving ivermectin could treat COVID-19 in real life. For a start, the dose required to kill the virus in a test tube was many multiples higher than the dosage approved for human use.
He discussed the results with a colleague, Mark Sullivan, and they agreed the next step was to check if the drug had the same effect in a dose safe for humans, which they conveyed to the researchers. It was a busy time for drug developers. Their minds moved on to other things.
So they were startled to learn on April 3 that the Monash study had been published in the Antiviral Research journal and announced in a press release titled “Lab experiments show anti-parasitic drug ivermectin eliminates SARS-Cov-2 in cells in 48 hours”. Ivermectin was safe, widely used and approved by the Food and Drug Administration (FDA) in the United States, the press release said. And it could potentially be used to fight COVID-19.
No cure for coronavirus: ivermectin tablets.Credit:Bloomberg
“It was incredibly hyped,” Dr Rayner said. “I knew it was going to start a fire.”
Eighteen months later, the evidence to show ivermectin cures COVID-19 in humans remains elusive, yet the fire ignited by that preliminary data has swept the world. Demand for the drug has skyrocketed, causing shortages. Veterinarians in Romania cannot get stock to treat dogs for scabies and ranchers in South Carolina cannot get enough to worm their cattle. Hospitals everywhere have reported overdoses. And people continue to die of COVID-19 while taking ivermectin.
“It’s not the best thing for Australia to become known for in terms of its contribution to the pandemic,” Dr Rayner said. “But that’s what it is, unfortunately. It has promoted vaccine hesitancy and people are dying because they’re taking a veterinary medicine that has not been proven.”
The fire spreads
Within weeks of the Monash study being published, research efforts were diverted to ivermectin and clinical trials were registered in several countries.
In April, the American healthcare analytics company Surgisphere published a preprint (meaning it was not subjected to peer review) that purported to show a strong positive association between ivermectin and COVID-19 patient survival. Surgisphere would later be exposed for scientific fraud and the data would be retracted, but only after it had been used in studies published in the high-profile New England Journal of Medicine and The Lancet. Some countries included ivermectin in treatment guidelines. Enthusiasm for the drug continued unabated.
An Iranian study showed an 80 per cent reduction in mortality. A Lebanese study showed reduced hospitalisation. Both were later found to contain major flaws. An influential Egyptian preprint found a 90 per cent reduction in mortality for patients taking ivermectin. The website later retracted the article amid fraud claims – some patients had died before the study started, among other concerns – but it had been cited by 30 other studies in the interim and included in meta-analyses that amplified its findings. The meta-analyses continue to be quoted as proof of the drug’s efficacy.
Belief in ivermectin as a treatment for COVID-19 has taken root despite a lack of scientific evidence.Credit:Bloomberg
By November 2020, the Monash study had been referenced in 450 journals. Dr Rayner addressed a conference on COVID-19 drugs organised by the American Association of Pharmaceutical Science and cautioned against using ivermectin. “We’re hoping [it] will not become the next hydroxychloroquine,” he said.
Then, on December 8, US physician Dr Pierre Kory appeared before a US Senate committee and described ivermectin as miraculous. “If you take it, you will not get sick.”
The clip was viewed over a million times, according to the Associated Press, before YouTube took it down – which only served to raise its profile. Conservative commentators cried censorship, anti-vaccination activists co-opted the drug for their purposes and ivermectin prescriptions surged by 2400 per cent over the pre-pandemic weekly average in the United States. In South Africa, a black market developed.
Kyle Sheldrick, a medical doctor and researcher at the University of NSW, has scrutinised 29 of the most influential studies on ivermectin and found the only studies to show a statistically significant improvement in mortality have turned out to be false. But belief in ivermectin has taken root.
“Once the idea that something works is in the popular domain, winding it back is almost impossible,” Dr Sheldrick said.
More recently, large clinical trials have shown marginal to zero benefit from ivermectin in COVID-19 patients. A Cochrane review, which is considered the gold standard in analysing scientific research, found there was not enough evidence to say whether ivermectin was effective against COVID-19. The TOGETHER trial, conducted by Canada’s McMaster University and involving 9000 patients, was terminated in August because it did not demonstrate a statistical effect.
Dr Sheldrick said it should not be surprising that so many of the first trials were flawed. “A lot of these trials came out incredibly quickly,” he said. “Legitimate trials take longer than fake trials.”
Last month, Australia’s Therapeutic Goods Administration (TGA) banned the off-label prescribing of ivermectin, citing the public health risk and national shortages created by a three- to four-fold increase in prescriptions.
Monash University has moderated its original press release to highlight disclaimers about the drug’s effectiveness and added a warning against ivermectin put out by the US’s FDA.
The university said in a statement it had always been clear that ivermectin was effective at killing the virus in a lab environment and further testing and clinical trials would be needed to establish the effectiveness of the drug at levels safe for humans. It still intended to conduct these trials.
“The university remains committed to making its research results known in a timely manner,” the statement said. “It is important that significant research findings – particularly during times of global crises like COVID-19 – are shared with the broader research and medical community to enable a greater effort to solve such problems.”
Promotion Down Under
Australia has its own ivermectin evangelists, most prominently Sydney gastroenterologist Thomas Borody. Dr Borody, who developed a therapy for peptic ulcers in the 1980s, has been a driving force behind faecal transplants and treated Labor politicians including Bob Hawke and Ian Macdonald.
Last year Dr Borody announced via press release that he had discovered a “cure” for COVID-19: a triple therapy of ivermectin, zinc and doxycycline. Ivermectin has since been championed by federal politicians Craig Kelly and George Christensen. Dr Borody’s research was quoted by the plaintiffs seeking to challenge mandatory vaccination in NSW.
“The biggest thing about this is no one will make money from this,” Dr Borody told 2GB’s Chris Smith in August 2020. “So there’s no big pharma behind it. I mean, one ivermectin tablet costs $2. It’s the cheapest, fastest way – with fewest side effects – to end this pandemic.”
Smith: “So you don’t have the lobbyists for the pharmaceutical companies banging on the door of the federal health minister, for instance?”
“That’s probably why it’s not getting through.”
The Herald does not suggest Dr Borody does not genuinely believe in ivermectin as a treatment, but he does stand to profit from the drug. The drug by itself is off-patent and therefore unprofitable, but his company Topelia Australia owns the global patent rights to his triple therapy and is raising money to support clinical trials.
A US-based trial found it had a 100 per cent survival rate among moderate to severe COVID-19 patients without hospitalisation and a rapid resolution of hypoxia. But the trial had 24 patients and Dr Sheldrick has pointed out that the patients in a synthetic “control” group were older and sicker than those who took ivermectin.
Dr Borody said patents were necessary because nobody would fund the trials otherwise. He has applied for 196 patents since the 1980s, covering inventions in his specialty area of gut health and extending to treatments for autism, obsessive-compulsive disorder and Parkinson’s disease. His peptic ulcer cure, which is now widely used, was initially derided as well, he said, and more than 600 COVID-19 patients had benefited from his triple therapy. “Essentially, this works.” The results are yet to be published.
The ‘Big Pharma’ conspiracy
The claim that Big Pharma has a vested interest in preventing ivermectin from being adopted as a COVID-19 treatment is a common thread among those who promote the drug. There is little argument pharmaceutical companies have no commercial incentive to repurpose off-patent drugs. The regulatory process is expensive because authorities require high-quality evidence that medicines are safe and effective.
Glenn Begley, an international biotechnology consultant, said the regulatory process was an essential element of bringing new medicines to market, but academic research was not subjected to the same rigour. Besides, academics had a vested interest too.
Dr Glenn Begley, left, with John Brumby, the chairman of the translational research group BioCurate. Credit:Photo: Peter Casamento
In 2012, Dr Begley reviewed all the oncology drugs his company Amgen had investigated over the preceding 10 years and found 90 per cent of the projects it had pursued based on studies published in major journals were later terminated. This was because the original researchers were unable to replicate their results when Amgen asked them to repeat the experiments blind. None of those papers had been retracted, he said.
“The real purpose for academics is to get their paper published,” Dr Begley said. “You’ve just got to get published to get the next research grant.”
Ivermectin was a case in point.
“The preclinical work about ivermectin should never have been published,” Dr Begley said. “The university was aware that there were problems with this research before it was published, but it went ahead anyway. And the truth is that in the fullness of time, Australia will be embarrassed by this story.”
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