Ivermectin: A Covid-19 Cure, Craze, or Curse?
On August 21, 2021 the FDA took the unusual step of publishing a warning against taking a veterinary formulation of Ivermectin to combat Covid-19. What made this warning particularly strange was that Ivermectin was an award-winning drug previously approved by the FDA and used for over 50 years. More recently, it had been the subject of more than three dozen small clinical studies, several of which supported its efficacy in treating Covid-19. In addition, its use as both a prophylactic and a therapeutic against Covid-19 had been the subject of a peer-reviewed report published by The American Journal of Therapeutics and had been advocated by a small group of highly respected medical practitioners.
Was this action simply the handiwork of a government agency corrupted by political influence and beholden to the large pharmaceutical companies that were reaping billions of dollars through their sales of Covid vaccines? These thoughts were certainly being expressed by those who viewed Ivermectin as a safe, readily available and low-cost answer to the coronavirus pandemic. The truth, though, was more complicated. This story of Ivermectin has its heroes and villains and the ultimate fate of the drug as a weapon in the fight against Covid-19 remains to be determined.
When the pandemic struck, efforts to combat it took place on many fronts. Public health officials publicized what little was known about the coronavirus pathogen and encouraged sharp reductions in social interaction as a means of impeding its spread. The Trump administration mobilized the nation’s pharmaceutical companies to develop vaccines and therapeutics by offering several billion dollars towards medical research and agreeing to purchase large quantities of vaccines and medicines that could win FDA approval. The nation’s hospitals began to develop protocols for treating patients who had contracted the virus, experimenting with ventilators to fight what they perceived to be a respiratory ailment and later turning to blood thinners when it appeared that the virus was interfering with blood flow to a multitude of organs.
Medical practitioners, faced with an onslaught of Covid patients, sought to identify the symptoms plaguing their patients and drew upon their knowledge of existing pharmaceuticals to treat those symptoms. Most didn’t have the luxury of time to pursue a cure or preventative or the research facilities with which to delve into the nature or properties of the pathogen that was afflicting their patients. Theirs was the process of reasoned trial and error which the medical profession had practiced for centuries. While the resources at their disposal were limited they were permitted to prescribe previously approved pharmaceuticals usually starting with those that had proven helpful in relieving the symptoms of other viruses and respiratory diseases.
No doctor wants to experiment on a patient with an unproven drug, but extreme conditions often require extreme measures especially when a patient’s survival is at stake. Responsible medical practitioners not only drew on their knowledge and experience but also on the efforts of local research laboratories to identify substances that could destroy or impede the reproduction of the pathogen in a test tube or petri dish. Even proceeding in this manner is fraught with danger, as substances that can eradicate a pathogen in a petri dish may not do so in the human body and can also do grievous harm to the patient. In short, the cure could turn out to be worse than the disease. Proceeding under such circumstances therefore requires courage, care and dedication to their professional pledge to “do no harm.”
Among those stepping into this abyss were five critical care specialists
who had previously collaborated to address medical problems. They were
Dr. Paul Marik, Chief of Pulmonary and Critical Care Medicine at Eastern Virginia Medical School and the author of the Handbook of Evidenced Based Critical Care;
Dr. Pierre Kory, the co-author of an award-winning medical textbook entitled Point of Care Ultrasound who served as the Critical Care Service Chief at the University of Wisconsin’s hospital in Milwaukee;
Dr. G Umberto Meduri, a Professor of Medicine at the University of Tennessee Health Science Center specializing in pulmonary conditions and considered the father of non-invasive ventilation;
Dr. Jose Iglesias, a critical care physician specializing in hypertension; and
Dr. Joseph Varon, a pulmonologist leading the coronavirus unit at Houston’s United Memorial Medical Center.
This group which assembled in March 2020 to address the Covid-19 pandemic served as the core of the eleven physicians who collectively assumed the title of “The Front Line Covid-19 Critical Care Alliance” more commonly referred to as “the FLCCC Alliance”.
The group first agreed that a corticosteroid (a class of steroids that imitate hormones produced by the adrenal cortex) should be at the core of the treatment they were seeking to devise. Building on a protocol that Dr. Marik had formulated for treating sepsis, the group put together a new drug cocktail which it labeled “MATH+” which was an acronym for its principal components (methylprednisolone, ascorbic acid, thiamine and heparin). This effort, however, never produced positive results.
By mid-April of 2020 Hydroxychloroquine, a previously approved drug for treating malaria, had been seized upon by a French medical researcher as a possible cure for Covid. President Trump, eager to find a way to to fulfill his prophecy that Covid would soon disappear, quickly endorsed Hydroxychloroquine and pressured the FDA to grant it an emergency approval. Dr. Kory also spoke out in favor of Hydroxychloroquine, an action he would later come to regret as comprehensive and disciplined clinical tests soon proved that drug to be both useless in fighting Covid and potentially harmful. Thus, there remained a void in the medical profession’s arsenal for combatting Covid.
From the very start of the pandemic, there also had been suggestions that Ivermectin might prove helpful in treating and/or preventing Covid. Ivermectin seemed an unlikely prospect as it was not an anti-viral agent but rather an anti-parasitic that had been developed by Merck, the pharmaceutical giant, for treating worms and other parasites in livestock. The livestock formulation, first marketed in 1981, contained 3,000 milligrams of Ivermectin so as to be sufficiently potent to treat 1,000 pound horses and cows. A few years later Merck developed and patented a 30 milligram formulation to treat lice, round worms, scabies, and other parasites in humans.
In the spring of 2020, an Australian medical researcher observed that a large dose of Ivermectin had killed the coronavirus in a petri dish. With an effective vaccine deemed to be months, if not years, away a few small clinical trials involving Ivermectin were begun around the world. Many of these were not randomized controlled trials (or RCTs), which the FDA required to approve a new drug. This prompted to the National Institute of Health (or NIH) to recommend that medical professionals not use Ivermectin to treat Covid patients. Nevertheless, since thousands of people were dying every day from Covid, the members of the FLCCC Alliance considered trials meeting FDA standards to be a luxury. In their minds, what was needed was some positive evidence that an agent could serve as an effective weapon in combatting Covid.
By October 2020 medical professionals began to take note of the growing number of small clinical trials involving Ivermectin. Even though the Pfizer and Moderna vaccines had shown great promise in their clinical trials conducted over the summer and would soon be the subjects of applications to the FDA for emergency approval, Ivermectin offered something entirely different. It was an approved drug which meant that it could be approved quickly once its efficacy in treating Covid was established. In addition, it was very cheap—even the version approved for human consumption cost only about $0.20 per dose compared to $2,000 per dose for the Pfizer and Moderna vaccines. Since the world was confronted with a pandemic, the virus would not be contained until it was brought under control throughout the world. That was not a job for those two vaccines the costs of which were prohibitive for those living in most underdeveloped counties.
Because none of the clinical trials involving Ivermectin included anything approaching the number of patients required to conclude that a drug is efficacious, medical researchers began to perform what is referred to as meta-analyses. That is, they combined the results of all of the clinical trials they deemed credible and applied statistical methods to reach an overall conclusion. This is a very tricky undertaking as different trials are performed under differing conditions, making it difficult for a clinician doing a meta-analysis to evaluate the reliability of each study’s data, let alone combine them effectively.
Members of the medical profession were not the only ones to take notice of Ivermectin. Many who had contracted Covid were scouring the internet in a quest for a cure. These individuals were not only desperate but usually under-informed. For the most part, their doctors were reluctant to prescribe Ivermectin because it had not been approved. They were also undoubtedly influenced by the fact that the two mRNA vaccines were on the cusp of receiving FDA approval and their costs were to be borne by the U.S. government. Public health officials also showed little interest in Ivermectin believing that the new vaccines would be sufficient to curb the spread of Covid within our borders. This left little incentive for the federal government to fund clinical trials of Ivermectin as it had done for the vaccine produced by Moderna.
Ivermetin’s prospects for treating Covid got a boost in November 2020 when a clinical trial involving Ivermectin conducted by Dr. Ahmed Elgazzar of Benhi University in Egypt was published in a peer-reviewed medical journal. This was by far the largest Ivermectin trial and involved approximately 400 patients. It showed a very high rate of efficacy in treating Covid patients, and because of its size, it completely skewed the ongoing meta-analyses. It also confirmed the FLCCC Alliance’s belief that Ivermectin could be efficacious in treating Covid. Adding to their confidence was a report of a medical researcher at Liverpool University in the U.K. who relied on the clinical data forming the basis of the FLCCC Alliance’s analysis and had reached a similar conclusion.
The group immediately sought to publicize its views regarding Ivermectin’s likely efficacy. This should have been welcome news to a nation which by October 31, 2020, had already suffered the deaths of approximately 240,000 of its citizens. In early December all members of the FLCCC Alliance, clad in their white lab coats, staged a press conference in front of the United Memorial Hospital in Houston. This was followed on December 4, 2020, with the appearance of Dr. Osgood on the Michael Brooks Show (a video podcast) to bring the Alliance’s preliminary conclusions to the attention of the medical profession.
On December 8, 2020, Dr. Kory testified before the Senate’s Homeland Security and Government Affairs Committee chaired by Senator Ron Johnson, the Senate’s leading anti-vaxxer. Senator Johnson repeatedly asked for Dr. Kory’s assessment of Ivermectin’s efficacy in treating Covid, ultimately prompting Dr. Kory to provide an unqualified affirmative response. That testimony was shown multiple times on YouTube and Fox News and is reported to have been viewed by more than one million people. Even though his statements before Senator Johnson’s committee were criticized as being overly optimistic and his Senate Committee testimony was later removed from YouTube, he and the remaining members of the FLCCC Alliance continued to stand firm in their belief in Ivermectin’s likely efficacy in treating Covid.
The FLCCC Alliance’s public relations efforts, however, soon bore fruit. While the Alliance wasn’t able to convince the U.S. government or the W.H.O. to fund clinical research involving Ivermectin, it was able to convince the NIH in early January 2021 that its previous negative assessment of Ivermectin’s efficacy was unwarranted. In response, the NIH changed its guidance regarding Ivermectin as a treatment for Covid patients from “adverse” to “neutral.” The NIH still declined to “recommend” the use of Ivermectin citing what it considered was insufficient data supporting the drug’s efficacy. Armed with this concession, the Alliance put out a series of press releases encouraging doctors to prescribe Ivermectin to their Covid patients. Their message, while intended for medical practitioners, was quickly picked up by right-wing media.
About the same time the FLCCC Alliance finalized its meta-data analysis and sent it to Frontiers, an open access web platform for peer reviewed medical findings. To the Alliance’s dismay, its submission was rejected citing “a series of strong unsupported claims based on studies with insufficient statistical significance.”
What may have been even more troubling was that the Alliance’s members had become the darlings of right-wing media. Touting the Alliance’s assertions, Fox News’s talk show hosts Laura Ingraham, Sean Hannity and Tucker Carlson, as well as Senator Johnson, regularly belittled the available vaccines which by then had received emergency FDA approval. Soon, mainstream media had begun to refer to the Alliance as a “fringe right wing anti-vax group.” Their reputation was not helped when those who listened to right-wing media began to eschew the available vaccines in favor of Ivermectin. Americans were not just taking the version of Ivermectin approved by the FDA for human consumption (largely because their doctors would not prescribe it); they were taking the much stronger version produced for animals and sold in animal feed stores. They were encouraged to do so by a woman who identified herself as a “Self Sufficient Momma” who produced a YouTube video entitled “Ivermectin Horse Paste” in which she demonstrated how to pare down the Ivermectin paste produced for animals. The problem wasn’t just that the animal version was up to 100 times stronger than the formulation authorized for human consumption -- it also contained numerous impurities that were toxic for humans. The Horse Paste video shortly received 160,000 views and Ivermectin soon became a hot topic on social media where users exchanged tips for how to obtain the drug.
Despite these developments, things were looking up for the FLCCC Alliance. On June 1, 2021 Michael Capuzzo, a journalist, published an article praising Ivermectin as “The Drug That Cracked Covid.” The article was filled with praise for Dr. Marik whom Capuzzo characterized as “a world-renowned clinical researcher” and “the second-most published critical care doctor in the history of medicine with more than 500 peer-reviewed papers and books.” Capuzzo’s article was soon followed shortly thereafter by the publication in the American Journal of Therapeutics of a report with a meta-data analysis similar to that of the Alliance and characterizing Ivermectin as “showing promise.”
Then things took a turn for the worse. In late June, a medical researcher in the U.K. published a scathing critique of the Egyptian study which was the cornerstone of the meta-analyses prepared by the Alliance and the study published in the American Journal of Therapeutics. It pointed out that the Egyptian study had plagiarized a section of its report from a news article, had “cloned” data relating to 79 of its 400 patients and that its data lacked internal consistency. In short, the credibility of Egyptian study was destroyed and never should have been incorporated in a meta-analysis.
While this had to be a devastating blow to the members of the Alliance, it had no apparent impact on the public at large. Amazon, having taken note of the large number of internet searches for Ivermectin, had begun offering tubes of 3,000 milligrams of the animal formulation on its website during the summer of 2020. Its August 2020 sales of Ivermectin totaled $184,073. A year later its monthly sales had grown to $3.2 million. Similarly, weekly prescriptions of Ivermectin for human consumption jumped from an average of 3,600 before the pandemic to 88,000 in one week in August 2021. Not surprisingly, calls to the nation’s poison control centers started to skyrocket prompting a warning by Mississippi’s chief medical officer against taking Ivermectin and, ultimately, the August 21st warning of the FDA.
Clearly, this story has its heroes and villains and their identities have not been readily apparent to the casual viewers of the evening news or social media. While the FDA has steadfastly refused to grant emergency approval for the use of Ivermectin in the fight against Covid, upsetting some, its actions were wholly justified. Ever since the 1950s when thalidomide caused thousands of children to be born with serious birth defects the FDA has made it exceedingly difficult for pharmaceutical companies to obtain approvals to sell their products. In fact, it’s not uncommon that the costs of achieving FDA approval for a new drug can exceed $100 million. FDA approval of Ivermectin even on an emergency basis was made less likely by the agency’s recent experience with having unwisely bowed to President Trump’s pressure to grant emergency approval in the case of Hydroxychloroquine, which it then had to withdraw a few months later. Also, by the time that any evidence of Ivermectin’s efficacy was assembled, the Pfizer and Moderna vaccines were in the final stages of being considered by the FDA alleviating any pressure on the agency to act hastily.
Similarly, the action of the NIH in not providing a positive recommendation for Ivermectin’s use to combat Covid was amply justified. The meta-analysis submitted by the Alliance to the NIH at the beginning of this year was heavily influenced by the Egyptian clinical trial which was later demonstrated to be unreliable. Also, by the time the NIH made its determination, Regeneron’s monoclonal antibody cocktail had been used on President Trump with astonishing success. The NIH also had to be concerned about recommending the use of an unproven therapeutic when the nation’s primary goal at the time was to promote the vaccination program then being ramped up. Recommending a therapeutic might have adversely impeded the progress of that program, and later experience has revealed that this was a valid concern. To its credit, the NIH is now funding a clinical trial involving Ivermectin which is being conducted by Duke University.
Although the doctors of the FLCCC Alliance have received some harsh criticism in the mainstream media, they are neither quacks nor charlatans. Far to the contrary, their actions were not only ethical but generally commendable. In the beginning they collaborated and searched diligently to find a way of treating their Covid patients when little was known about the virus. Even after the efficacy of the Pfizer and Moderna vaccines had been established, they rightly understood that those vaccines were well beyond the economic reach of most of the world’s population and that the need for a low-cost alternative cure for Covid remained. They were therefore amply justified in their efforts to engender further research of Ivermectin’s efficacy. Their principal error was in allowing their zeal to find such a cure to blind them from the deficiencies in the data they were incorporating in their meta-analysis.
It should be understood that the Alliance’s faith in Ivermectin may yet be found to be justified. There is still an enormous need for a low-cost alternative to the very expensive vaccines which the U.S. government is currently making available to its citizens. As long as the virus remains widespread in underdeveloped countries, it can continue to mutate and threaten people all over the world, even those of us who have been given free access to the vaccines. The problem is that the costs of definitive clinical trials are large and the economic rewards for creating a drug for the world’s poor are not large. In addition, with highly effective vaccines already in existence, there could be difficulties in conducting clinical trials. Realistically, they would have to be conducted in countries in which the existing vaccines are not economically available. To be sure, there appears to be no shortage of individuals in this country willing to be treated with Ivermectin. However, there may be few doctors willing to enroll them in clinical trials in which they will receive either an unproven drug or a placebo given that there are effective drugs already available.
A story in which hundreds of Americans have had to seek help in the nation’s emergency rooms for overdoses of an unproven drug and in which millions have refused to avail themselves of government-funded, extraordinarily effective vaccines (with many dying as a result) cannot be said to be without villains. However, it should be understood that there is a clear distinction to be drawn between those who have conveyed information about a potentially promising new drug, and those who have encouraged others to take an unproven drug when alternatives that have been proven efficacious are readily available. Heading this latter group are those who have done so for their own personal or political gain, and they bear the brunt of the blame for this disaster.
For the members of the FLCCC Alliance Ivermectin has been an unmitigated curse. All of them have been castigated as quacks and charlatans and falsely accused of being right-wing anti-vaxxers. They have also been wrongly accused of having a financial motive for encouraging the use of Ivermectin. At least one of them has lost his position in the hospital where he was practicing. Such are the dangers of allowing yourself to become a pawn in a game of political chess. This is a sad story for the members of the FLCCC Alliance as well as for others who set out to make the world a better and safer place.