One of the world’s biggest vaccine proponents and strident defender of intellectual property rights is funding, directly and indirectly, large trials into cheap, off-patent, off-label COVID-19 treatments, including ivermectin.
The evidence backing ivermectin’s efficacy against Covid-19 continues to stack up, even as most health authorities refuse to approve its use. The last two months have seen the publication of three peer-reviewed meta-analyses demonstrating clear benefits. A review by Pierre Kory et al summarised findings from 18 randomized controlled treatment trials, concluding that ivermectin produced “large, statistically significant reductions in mortality, time to clinical recovery, and time to viral clearance.” Another study, led by Doctor Andrew Hill, a well-respected international medical researcher reported a 56% reduction in mortality together with favourable clinical recovery and reduced hospitalisation.
A third study, by Andrew Bryant et al, analysed the existing data from clinical trials according to conservative Cochrane meta-analysis standards — a gold-standard in science. Published in the American Journal of Therapeutics, the study found that “ivermectin prophylaxis reduced COVID-19 infection by an average 86%”. The study concluded that “large reductions in COVID-19 deaths are possible using ivermectin”, adding that “the apparent safety and low cost suggest that ivermectin is likely to have a significant impact on the SARS-CoV-2 pandemic globally.”
Still in Limbo
But national and supranational health authorities continue to drag their feet. The US Food and Drug Administration, together with the European Medicines Agency (EMA) and the World Health Organization, insist that there is still not enough good quality data to approve ivermectin as an off-label treatment against Covid. Its use, they say, should therefore be restricted to well-designed, randomised control trials.
Over 20 countries around the world, including India, Bolivia, Mexico and Slovakia, have ignored that advice and are using the medicine, to some degree or another, largely with significant success. The latest country to do so is Indonesia, which is in the grip of its biggest wave of infections to date. In most countries, however, the drug is still in limbo as their respective health authorities await the outcome of large randomised controlled trials.
The problem is that large randomised trials are prohibitively expensive, costing millions of dollars to conduct. As a result, they tend to be funded by large pharmaceutical companies seeking FDA or EMA approval for the drugs they themselves have developed. It also makes it difficult to secure new indications for generic medications that are already approved for other purposes. After all, who is willing to invest millions of dollars testing a drug that is likely to generate little, if any, financial return?
But with the world fighting a losing battle against a fast-spreading, rapidly evolving coronavirus that has sent the global economy spinning, desperate times call for desperate measures. Money has been found and mobilised. According to Hill et al, there are at least five large, placebo-controlled clinical trials on the use of ivermectin for COVID-19 currently underway.
One of them, dubbed the TOGETHER trial, is being conducted at McMaster University in Ontario, Canada. The trial has been running since last summer. The goal, according to the trial’s official website, is to “identify which repurposed therapies are most effective, in order to slow the pandemic while many countries await the delivery of vaccines.”
The trial has already tested and “dropped” hydroxychloriquine, lopinavir/ritonavir (an antiretroviral medication used in the treatment and prevention of HIV/AIDS) and metformin (an anti-diabetes medication). It is currently testing fluvoxamine (an anti-depressant), interferon-lambda (a regulator of intenstinal viruses), doxazosin (used to treat prostatic hyperplasia and hypertension) and ivermectin and will report its findings in the coming months.
There’s only one potential problem: where it gets its money.
The Together Trial has received millions in funding from three main sources: the Rainwater Foundation; Fast Grants, an American charity that provides funding for scientific research whose donors include Arnold Ventures, The Chan Zuckerberg Initiative, Jack Dorsey and Elon Musk; and last but not least, the Bill and Melinda Gates Foundation.
The Gates Foundation, as readers are no doubt aware, is one of the world’s biggest backers of vaccine research, as well as the second largest funder of the World Health Organization (WHO). It is also heavily invested in large pharmaceutical companies, including Pfizer and BioNTech, the joint manufacturers of the world’s most profitable Covid-19 vaccine, and Merck, the original manufacturer of ivermectin which has an antiviral compound, molnupiravir, in Phase 3 clinical trials for COVID-19.
As well as founding and funding the Vaccine Alliance (GAVI), the Gates Foundation is a passionate defender of pharmaceutical companies’ intellectual property rights. For months the world’s largest private foundation blocked attempts to temporarily lift coronavirus vaccine patent protections, preventing poorer countries from gaining cheaper access to COVID-19 vaccines, until it was finally forced to reverse course. As for McMaster, it is developing homegrown vaccines to fight COVID-19 in its “specialised lab and production facilities.”
In other words, an organisation that is hugely committed and invested in vaccine development is running one of the world’s largest clinical trials into one of the biggest threats facing COVID-19 vaccines: existing off-label medicines. To top it off, the trial is being part-financed by arguably the world’s biggest vaccine cheerleader whose interests are closely aligned with the world’s biggest pharmaceutical companies, some of which it is directly invested it.
The potential for conflicts of interest is huge. If a cheap, off-patent drug like ivermectin were approved for use against COVID and if it worked as effectively and as safely as most trials suggest, it would pose a direct threat to novel treatments being rolled out by pharmaceutical companies whose safety data is no match for ivermectin’s. It could also even jeopardise the emergency use authorisation granted to the COVID-19 vaccines, one of the basic conditions for which is that there are no alternative effective treatments available for the disease. As such, if ivermectin or some other promising medicine were green-lighted, the vaccines could be stripped of authorisation.
Pharmaceutical companies have a long track record of gaming the drugs trials they themselves finance and design. Unfortunately, most trials these days are industry funded. In a 2013 article for Scientific American Ben Goldacre showed how that could dramatically skew trial outcomes.
In 2010, three researchers from Harvard and Toronto found all the trials looking at five major classes of drug—antidepressants, ulcer drugs and so on—then measured two key features: were they positive, and were they funded by industry? They found over five hundred trials in total: 85 per cent of the industry-funded studies were positive, but only 50 per cent of the government funded trials were. That’s a very significant difference.
In 2007, researchers looked at every published trial that set out to explore the benefit of a statin. These are cholesterol lowering drugs which reduce your risk of having a heart attack, they are prescribed in very large quantities, and they will loom large in this book. This study found 192 trials in total, either comparing one statin against another, or comparing a statin against a different kind of treatment. Once the researchers controlled for other factors (we’ll delve into what this means later), they found that industry-funded trials were twenty times more likely to give results favoring the test drug. Again, that’s a very big difference.
We’ll do one more. In 2006, researchers looked into every trial of psychiatric drugs in four academic journals over a ten-year period, finding 542 trial outcomes in total. Industry sponsors got favorable outcomes for their own drug 78 per cent of the time, while independently funded trials only gave a positive result in 48 per cent of cases. If you were a competing drug put up against the sponsor’s drug in a trial, you were in for a pretty rough ride: you would only win a measly 28 per cent of the time
“Those who design the trials and control the data also control the outcome,” says Tess Lawrie, a British medical researcher and doctor who led the Bryant et al meta-analysis. “So this system of industry-led trials needs to be put to an end. Data from ongoing and future trials of novel COVID treatments must be independently controlled and analyzed. Anything less than full transparency cannot be trusted.”
Usually the goal of a trial is to achieve a favorable outcome for the drug under trial. This can be done through a number of means, including ignoring certain inconvenient data, using subjective outcomes or changing outcomes in the middle of the trial. In the case of the TOGETHER trial, the potential risk of bias is in the opposite direction — i.e. achieving an unfavorable outcome. This can be done by, say, setting unrealistic magnitudes of benefit, stopping the trial early, using easily recognizable placebos so people can tell the difference or giving inadequate or toxic doses.
The Gates’ Foundation position on ivermectin is not exactly clear. Most organizations tied to the foundation have largely taken an antagonistic stance to the drug — at least in its current off-patent form. GAVI, for example, recently published an article titled “Ivermectin: Why a Potential COVID Treatment Isn’t Recommended”. The article includes the totally erroneous claim that the US National Institutes of Health (NIH) does not recommend the drug. As we’ve reported before, the NIH has taken a neutral stance on IVM, neither advocating for or against its use. This is the reason why it’s possible, albeit difficult, to get ivermectin prescribed for COVID in the US, unlike most other advanced Western economies.
In a curious twist, at the same time that GAVI is publishing articles cautioning governments and doctors against using ivermectin against COVID, the Bill & Melinda Gates Foundation is quietly funding work on an injectable form of the drug. The project, developed by French biotech company Medincell, was officially announced on April 6, 2020. That was just after lab researchers in Australia had discovered that a single treatment of ivermectin could deliver a 500-fold reduction in virus cell culture after just 48 hours.
Medincell had already been studying Ivermectin in the context of malaria. According to the company’s own press release, its program “aims at developing a long-acting injectable Ivermectin formulation for several months to protect people who are not infected with Covid-19 in order to break the virus chain of transmission. Such a tool could play a decisive role in the management of Covid-19 pandemic, by enabling many people around the world, especially those most exposed and at risk, to protect themselves.”
Since Medincell uses a long-acting injectable technology to deliver the drug, it will presumably hope to secure a patent on its finished product, despite the fact that ivermectin has been off-patent for years. In April this year, the company announced that its clinical trial had confirmed the safety of administering ivermectin against COVID. Yet health authorities around the world, including the Gates-funded WHO, continue to call for more data.
Conflicts of Interest
The person leading the TOGETHER trial, Edward Mills, is a McMaster associate professor as well as the clinical trial advisor for the Gates Foundation. Asked for comment on potential conflicts of interest, Mills denied that the Gates Foundation was having any “say on the conduct of the trial” even though he himself is leading the investigation and is employed by the Gates Foundation.
Another big trial into repurposed drugs, the so-called PRINCIPLE trial, is taking place at Oxford University, which developed the AZ vaccine. Once again, the conflicts of interest are glaring.
The University of Oxford is heavily invested in the immunotherapeutics products and vaccines being developed by Vaccitech, a spin-out from the university’s Jenner Institute. It has also received hundreds of millions of pounds of funding from the Bill & Melinda Gates Foundation, including a grant for the objective of maintaining two websites that provide data regarding substandard and falsified medicines. As NC reported a few months ago, the foundation was instrumental in dissuading Oxford University from donating the rights to its coronavirus vaccine to any drugmaker, which would have made the vaccine cheaper and more accessible in poorer countries.
In a letter to the lead investigators of the PRINCIPLE trial, the Front Line COVID-19 Critical Care Alliance (FLCCC), a group of widely published critical care physicians and scholars, and the British Ivermectin Recommendation Development Group (BIRD), a U.K. based group of medical and scientific experts from more than 16 countries, questioned the ethics of the trial, given that half of the participants who are suffering from COVID will receive NO treatment. Some could end up dying — completely unnecessarily, the letter says, given “the latest research shows beyond a doubt that ivermectin is an effective treatment for COVID-19 in all stages of the disease.”
The letter also raises serious concerns about the quality of data the trial is likely to produce:
The trial intends to observe the antiviral properties of ivermectin in patients that have been showing COVID-19 symptoms for up to 15 days. It is well known that the virus naturally clears the body in 5 to 7 days. Measuring antiviral properties of a treatment when the virus may have cleared the body naturally is unlikely to be useful for providing reliable evidence or clinical guidance.
One can only hope that the concerns raised by FLCCC and BIRD’s joint letter are unfounded, and that: a) nobody dies in the trial; and b) its processes are not rigged to ensure that the findings come out negative. Such an outcome would no doubt be reported massively and uncritically by the media. That could be enough to kill off all hopes of using the medicine against COVID — at least in its cheap off-patent form — not only in the countries that aren’t using it yet but even some of those that are. The result would be many more lives needlessly lost as well as the loss of one of the potentially most important lines of defence we have against this pandemic.