Ivermectin: the rest of the story

While hospitalized, notes the article, Smith’s “condition began to decline” to the point where he was “sedated, intubated and placed on a ventilator on Aug. 1. Several subsequent serious infections left Smith with a roughly 30% chance of survival by Aug. 20 when he remained on the ventilator in a medically induced coma.”

Jeffrey Smith’s wife, Julie Smith, filed a lawsuit against the hospital Aug. 20 to compel the hospital to treat her husband with ivermectin, which costs pennies on the dollar and is available as a tablet that most consumers can take at home. One day later, the U.S. Food and Drug Administration (FDA) put out a statement on Twitter implying ivermectin was only for farm animals and stated that “using the drug ivermectin to treat COVID-19 can be dangerous and even lethal.”

You are not a horse. You are not a cow. Seriously, y'all. Stop it. https://t.co/TWb75xYEY4

— U.S. FDA (@US_FDA) August 21, 2021

Five days after that, the Centers for Disease Control (CDC) issued a health advisory, noting “Ivermectin is not authorized or approved by FDA for prevention or treatment of COVID-19” and “the National Institutes for Health (NIH) COVID-19 Treatment Guidelines Panel has also determined there are currently insufficient data to recommend ivermectin for treatment of COVID-19.”** (See information regarding the makeup of the NIH COVID-19 treatment panel at the end of this piece.)

When The Ohio Press Network (OPN) contacted the CDC for additional insight on ivermectin, a press officer repeated the advisory, which includes the above statement.

The CDC advisory also referenced a “three-fold increase” in poison control center calls about the drug, but, save for two summaries of individual cases, the CDC did not supply any actual data surrounding the numbers of calls.

Suddenly, Ohioans who’d already been prescribed ivermectin (not just for active COVID cases) found pharmacies statewide either refusing to fill the prescriptions or completely out of stock of the drug and unsure when it might become available again. But in Butler County, the temporary court order took effect, and Jeffrey Smith began receiving ivermectin.

By Sept. 6, Julie Smith and UC Health West Chester were back in court, and the hospital was awarded the right to terminate Jeffrey Smith’s ivermectin treatment.

The judge in that second case made a special note that Smith’s attorney did not use the Right to Try Act in attempting to secure permission to use the drug. President Trump signed this bill into law May 30, 2018, as “another way for patients who have been diagnosed with life-threatening diseases or conditions who have tried all approved treatment options and who are unable to participate in a clinical trial to access certain unapproved treatments,” per the FDA’s official Fact Sheet).

By then, though, Smith had already received roughly 13 days’ worth of ivermectin and his attorney, Ralph Lorigo of New York—who has filed and won multiple lawsuits compelling hospitals to administer ivermectin to patients with COVID-19 complications—was quoted as saying Jeffrey Smith had “been helped by the medication” and that “the hospital has since told Julie Smith that they’re ready to wean him off the ventilator.”

This turn of events has left many Ohioans confused and wondering whether ivermectin is actually “dangerous; “a mere “dewormer,” as government agencies and media outlets have implied; or a promising, effective and inexpensive COVID-19 treatment.

As breakthrough COVID-19 cases increase among the vaccinated both overseas and here, Ohioans need to know the full story.

HORSE DEWORMER OR MIRACLE DRUG?

Per this February 2011 article from the NIH database by Andy Crump and Satoshi Omura—the Japanese scientist who would win the Nobel Prize in 2015 for the discovery of ivermectin—ivermectin was discovered in the late 1970s and derived “solely from a single organism from Japanese soil.” It was initially used to treat animals with parasites, but in 1988 doctors began treating humans with it as well. Merck held the original patent for the drug, which expired in 1996.

Since the late 1980s, billions of people have taken the drug worldwide. Per this 2017 press release, Merck donated more than 2.8 billion treatments of MECTIZAN (ivermectin) globally to treat river blindness between 1987 and 2017. After partnering with the Bill and Melinda Gates Foundation for research in 2017, the company committed to use the same medication to treat “up to an additional 100 million people per year through 2025” for lymphatic filariasis, another parasite-borne disease which, like COVID-19, interferes with the body’s own immune response.

By 2011, 48 countries worldwide were using ivermectin to treat their citizens, note Crump and Omura. The pair calls ivermectin a “wonder drug” and “one of the greatest medical accomplishments of the 20th century.” It is “the essential mainstay of two global disease-elimination campaigns that should soon rid the world of two of its most disfiguring and devastating diseases, which blight the lives of billions of the poor and disadvantaged throughout the tropics.”

Ivermectin is also present today on the World Health Organization (WHO)’s list of essential medicines and has been used to treat other diseases globally like Zika, influenza, Ebola (per this comment in the Lancet) and Lyme disease (per author Bryan Rosner, Freedom From Lyme Disease).

“Ivermectin is used around the world for different reasons,” said Dr. Jay Bhattacharya, an epidemiologist, physician and Stanford Medical School professor, in an interview with OPN. “It’s a great drug for its intended purpose, and there’s lots of strong evidence for those purposes.” He also notes, though, that “there are two competing meta-analyses that I’m aware of, about the effects of ivermectin on treating COVID patients, and they come to opposite conclusions.” For this reason, he says, “We should have by now a high-quality study for ivermectin, but instead what we have is that it’s almost taboo to talk about these drugs or evaluate them at all.”

IS IVERMECTIN DANGEROUS?

As previously noted, Merck has treated billions of people worldwide with the drug since the late 1980s.

Per both this and this CDC document, the United States currently administers ivermectin to all refugees who enter the country from Latin America, the Carribbean, Asia, the Middle East and Africa. The U.S. has been administering this “presumptive treatment” protocol, including other drugs, to refugees since Feb. 6, 2019.

When Hamilton County Common Pleas Judge Michael Oster ruled that UC Health West Chester Hospital could not be forced to administer ivermectin to Smith, he noted, “This court is not making a decision on the effectiveness of ivermectin. Rather, the question is, ‘Has the plaintiff met her burden to be entitled to a preliminary injunction under Ohio law.’”

Crump and Omura’s article points out, “Ivermectin has continually proved to be astonishingly safe for human use. Indeed, it is such a safe drug, with minimal side effects, that it can be administered by non-medical staff and even illiterate individuals in remote rural communities.”

On Dec. 8, 2020, Dr. Pierre Kory, a pulmonary and critical care specialist, testified before the Homeland Security Committee, noting, “The safety of ivermectin is nearly unparalleled given its near nil drug interactions along with only mild and rare side effects observed in almost 40 years of use and billions of doses administered.”

HOW DO MEDICAL STUDIES AND DOCTORS WHO TREAT COVID PATIENTS USING IVERMECTIN SAY IT WORKS?

Per Kory and Dr. Paul Marik, pulmonary and critical care medicine division chief and professor of internal medicine at Eastern Virginia Medical School, “studies show that one of [ivermectin’s] several anti-viral properties is that it strongly binds to the spike protein, keeping the virus from entering the cell.”

This American Journal of Therapeutics article, which cites 84 supporting documents and/or studies and is authored by Kory, Marik and three other doctors, states that “ivermectin has potent anti-inflammatory properties with in-vitro data demonstrating profound inhibition of both cytokine production and transcription of the most potent mediator of inflammation. Ivermectin significantly diminishes viral load and protects against organ damage in multiple animal models when infected with SARS-CoV-2 or similar coronaviruses. Ivermectin prevents transmission and development of COVID-19 disease in those exposed to infected patients. Ivermectin hastens recovery and prevents deterioration in patients with mild to moderate disease treated early after symptoms. Ivermectin hastens recovery and avoidance of ICU admission and death in hospitalized patients. Ivermectin reduces mortality in critically ill patients with COVID-19. Ivermectin leads to striking reductions in case-fatality rates in regions with widespread use.”

Multiple media outlets have spoken out against Kory and Marik, including this Business Insider piece, which describe them as “fringe doctors [who] created the myth that ivermectin is a ‘miracle cure’ for COVID-19.”

IVERMECTIN & COVID-19 OBSERVATIONS

The first observational study of ivermectin for COVID-19 treatment in the world happened at four Broward Health hospitals in Florida and was titled “Use of Ivermectin Is Associated With Lower Mortality in Hospitalized Patients With Coronavirus Disease.” Observational studies investigate people already taking a drug or intervention, rather than giving it to a group representative of the population.

Explored in the March 2021 Japanese Journal of Antibiotics, the study found that “the mortality rate of 173 patients in the ivermectin group was 15.0%, which was significantly (p=0.03) superior to 25.2% of 107 patients in the control group. This result was published as a medRxiv preprint on June 6, 2020, but its value was not recognized at the time because it had not yet been peer reviewed. Following peer review, it was published without any changes in the prestigious journal Chest on Oct. 13.”

The Japanese Journal of Antibiotics goes on to note that “a total of 91 trials in 27 countries has been recorded… Furthermore, by Feb. 27, the results of 42 clinical trials, including approximately 15,000 patients (both registered and unregistered studies) have been subjected to a meta-analysis after exclusion of biasing factors. It was found the 83% showed improvements with early treatment, 51% improved during late-stage treatment, and there was an 89% prevention of onset rate noted. Since it is a meta-analysis based on 42 test results, it is estimated that the probability of this comprehensive judgment being a mistake is as low as 1 in 4 trillion.”

Today, there are active clinical trials for ivermectin as a COVID-19 treatment happening in 27 countries, including Italy, Turkey, the UK, Brazil, India, Argentina and Singapore.

IVERMECTIN’S UPHILL BATTLE

Days after Kory’s Dec. 8 testimony at a Homeland Security Committee meeting, the NIH adjusted its position on the use of ivermectin in COVID-19 treatment from “against” to “neither for nor against,” a change that Kory called an “upgrade” and that allowed U.S. physicians to begin prescribing the drug to COVID-19 patients.

On Aug. 26, 2021, the CDC issued a health alert that noted that “data from adequately sized, well designed and well conducted clinical trials are needed to provide evidence” for whether or not ivermectin works as a COVID-19 treatment.

But authors of the March 2021 Japanese Journal of Antibiotics article claim that when Japan’s Kiasoto University “asked Merck to conduct clinical trials of ivermectin for COVID-19 in Japan… the company said it had no intention of conducting clinical trials.”

In an interview with OPN, Dr. Martin Kulldorff, a member of the FDA’s Scientific Council for Drug Safety and Risk Management and biostatistician, epidemiologist and professor of medicine at Harvard Medical School, said, “The only drug on which we have some actually reliable information is remdesivir, because it’s proprietary, and the patent hasn’t expired, so there was an incentive for the pharmaceutical company to run those trials originally. But for other drugs, there is no incentive. Therefore, it falls on NIH and NIAID (National Institute of the Allergy and Infectious Diseases) to run those trials, which they never did. That was a huge mistake by the government not to quickly run a bunch of these trials for different types of treatments.”

“Now,” said Dr. Robert Malone, a virologist, immunologist and researcher who contributed to the development of mRNA vaccine technology, during an interview with Jan Jekielek on American Thought Leaders, “we’re in this odd position where we have groups of doctors who’ve developed a treatment protocol they believe works when implemented early. But they’re not being allowed to prescribe. Pharmacies are not being allowed to fill prescriptions. Physicians are not being allowed to practice what they believe to be good medicine in hospital settings.”

WHY ARE OHIOANS HAVING A HARD TIME FINDING IVERMECTIN AT LOCAL DRUG STORES?

The Ohio Board of Pharmacies’ Cameron McNamee said ivermectin “is currently permitted to be dispensed in the state” and is not on the FDA’s drug shortage lists. He also said, “with off-label prescribing of drugs, physicians are given a wide latitude in that space by federal law” and noted that “we had not put out any guidance about ivermectin prescribing until we put out the CDC health alert” against its use after receiving “a notice from the Ohio Health Department (ODH) asking us to distribute this to our licensees.”

An ODH representative noted they do not oversee the state Board of Pharmacy as both organizations are state agencies under the administration of Gov. Mike DeWine. She also noted both the FDA and CDC “have warned against the use of ivermectin to treat COVID-19.”

While no one in Ohio seems to be publicly mandating that ivermectin not be used, and while it is technically not in shortage, ivermectin is still somehow missing from, or being kept from sale at many big-box drug stores both in Ohio and nationwide.

Walgreens did not return a request for comment. A CVS representative noted the FDA’s recommendation against ivermectin for COVID-19 but also stated, “We do not have a policy that restricts our pharmacies from filling prescriptions for ivermectin” and “our pharmacists are empowered to use their professional judgment when reviewing a prescription and a prescriber’s diagnosis.”

The only clue here comes from Merck itself, ivermectin’s original patent holder and a major supplier of the drug worldwide. The pharmaceutical company released this statement on Feb. 4, 2021, stating they do not believe ivermectin is effective in treating COVID-19. Four months after that, Merck released this statement, announcing the development of Molnupiravir—in collaboration with the U.S. government. The drug is a new “investigational oral antiviral candidate for treatment of mild to moderate COVID-19.” The statement makes special note that the “U.S. government commits to purchase approximately 1.7 million courses of Molnupiravir upon issuance of Emergency Use Authorization or approval by the U.S. Food and Drug Administration.”

Per these publicly stated FDA guidelines, the FDA will only grant Emergency Use Authorization for a drug like Molnupiravir “when certain criteria are met, including if there are no adequate, approved and available alternatives.”

Also, per Harvard Medical School physicians Drs. Wendy Chen and Michelle Holmes in a 2014 New York Times op-ed, “Clinical trials are typically conducted on drugs developed by labs seeking huge profits. No one stands to make money off aspirin, which has been a generic drug since the Treaty of Versailles in 1919, and which costs less than $6 for a year’s supply.”

Regarding ivermectin, Dr. Kulldorff noted, “We are now in a situation where we don’t have solid evidence whether a particular treatment works or not. If we had conducted those thorough trials, randomized trials, then we would know for sure. We can’t blame the scientists, because normally [a scientist] writes a grant application and, half a year later, it’s reviewed. If everything goes well, after 10-12 months you’ll be funded to do a three-or-five-year project. That’s not the time scale we need for a pandemic. It’s really a mistake of the NIH and NIAID that they didn’t initiate the launch of these trials.”

Dr. Bhattacharya echoed Kulldorff’s sentiment that the federal public health agencies should have stepped up. “I think that actually is a scandal. Because ivermectin is off-patent, it’s the NIH’s job to evaluate the effectiveness of products off-patent just like it’s Gilead [Science]’s job to evaluate whether remdesivir works. The NIH has invested in one single ivermectin study, if I’m right, that is due to be done in December 2023,” continued Bhattacharya. “There should have been many more evaluations, high quality randomized evaluations, sponsored by the NIH and the NIAID.”

When asked to comment on ivermectin for this piece, Merck’s global media relations team said, “We have nothing to add beyond our statement” from Feb. 4.

IF GOVERNMENT AGENCIES AND THE DRUG MAKER AREN’T ADVOCATING FOR THE USE OF IVERMECTIN, WHO IS?

Per the Japanese Journal of Antibiotics article, when Merck refused to conduct a clinical trial of ivermectin, Kitasato University decided to conduct a doctor-initiated, clinical trial. “It was then found, somewhat surprisingly, that 14 trials were already registered on ClinicalTrials.gov by the May 25. Among them, except for two trials in the United States, all studies were conducted in developing countries with a large number of poor patients. Looking closely at the protocols of the trials in these developing countries, all of them are doctor-initiated.”

Per mRNA technology researcher Dr. Robert Malone, “Doctors who have been at the forefront of early intervention protocols—we’re coming together, we’re being brought into contact with investors, donors that are not comfortable with the current public policy and are very interested in enabling these alternate strategies and their availability.”

WHY SHOULD BOTH VACCINATED AND UNVACCINATED PEOPLE CARE ABOUT IVERMECTIN?

While President Biden blamed unvaccinated people for increased cases in his Sept. 9 speech, Malone said in the interview with Jekielick that over-administration of the vaccine itself may be to blame, noting a “universal vaccination strategy could risk the creation of a virus strain that will be able to evade the vaccine.”

Malone calls these strains “escape mutants” and notes that such “virus isolates are no longer as susceptible to the control of infection and spread provided by the immune response generated by the vaccine.” Already, he adds, “we are seeing signs of the emergence of these escape mutants.”

In short, a universal vaccination campaign—versus a targeted, or selective one—as advocated by Dr. Kulldorff, Dr. Bhattacharya, epidemiologist and Oxford University professor Dr. Sunetra Gupta; and dozens of others doctors and medical academics from places like Duke University, Tel-Aviv University, Tufts University, University of Cambridge, Baylor University, the University of Arizona and the University of Edinburgh, will likely have the tragic and unintended consequence of putting “at risk the very people who need the vaccine the most,” says Malone.

The evasive strain concept is not new (see this 2018 Quanta magazine piece titled “Vaccines Are Pushing Pathogens to Evolve”). Following that logic, it’s entirely possible that widespread administration of booster shots—which the FDA recommended against Sept. 17 and which 18 international vaccine experts, including two recently resigned FDA officials, warned against in this Sept. 13 Lancet article—may only increase the number of mutants. Kulldorff noted that vaccinations leading to mutated variants is “speculation because we don’t know whether that’s going to happen or not. But it’s not an unreasonable thing to say.”

EDITOR’S NOTE:

In a phone interview, Julie Smith’s attorney Ralph Lorigo said, since Labor Day, when the court revoked forced dispensation of ivermectin, Jeffrey Smith’s condition has been “up and down.” According to Lorigo, Julie Smith is working to withdraw her husband from UC Health West Chester Hospital and gain admittance to United Memorial Medical Center in Houston, Texas, under the care of Dr. Joseph Varon.

*Supporting information regarding remdesivir:

Gilead Science’s remdesivir, which is FDA approved to treat COVID-19, costs thousands of dollars and can only be administered in hospital. It has also been called a failure in this July 12 American Society for Microbiology article and is linked in COVID-19 patients to:

• “a 20-fold increased risk of ARF [Acute Renal Failure]” (per this 2020 study published by the American Society for Clinical Pharmacology and Therapeutics, which compared remdesivir to hydroxychloroquine and two other drugs) and

• high rates of respiratory failure, the “need for mechanical ventilation” and elevated liver enzyme levels indicative of damage or disease (per Table 3 in this study on remdesivir for COVID-19 patients, which shows that between 70% and 74% of nearly 400 COVID-19 patients who took remdesivir experienced “adverse events”).

Even the WHO recommends “against the use of remdesivir in hospitalized patients,” noting that the drug includes the “need for mechanical ventilation” and offers “no important effect on mortality.”

“On the whole, my impression from the clinical data is that remdesivir has not actually lived up to what it promised,” said Dr. Bhattacharya. “It is not a very effective treatment for hospitalized COVID patients. It is certainly not a cure. Given the weak evidence, I think it has ended up being overused. It’s led to people being hospitalized to get it who probably didn’t need to be hospitalized.”

Remdesivir was originally developed to treat Ebola but this randomized, controlled 2019 trial whose results were published in the New England Journal of Medicine shows that more than 80% of Ebola-infected study participants with a high viral load who were treated with remdesivir died. The drug was pulled from the study.

**Supporting information regarding the NIH Panel on COVID-19 Treatment Guidelines:

Per this NIH document, between May 2019 (seven months before the COVID-19 pandemic officially began) and March 2020, this panel was comprised of 50 people, 38 of whom had no financial ties to “companies related to COVID-19 treatment or diagnostics.” Seven pharmaceutical companies total were represented via financial relationships with board members and four people on this panel had ties to multiple pharmaceutical companies; Duke Associate Professor of Medicine Susanna Naggie had the most, with three.

Per this NIH document, last updated Aug. 4, 2021 (five months beyond its stated reporting period, April 1, 2020 and March 31, 2021), the panel expanded to 62 members. It still includes 38 people with no financial ties to “companies related to COVID-19 treatment or diagnostics,” but now 30 pharmaceutical companies are represented via financial relationships with board members. Of the 13 people on this panel who have ties to multiple pharmaceutical companies, infectious diseases doctor Judith Aberg has the most with 10 (on the first panel, she had two).