Why Isn’t Ivermectin Being Widely Researched and Utilized?

Why Isn’t Ivermectin Being Widely Researched and Utilized

On November 13, a scientific review manuscript was posted to OSF, a medical pre-print server by Pierre Kory, MD, of the Front Line COVID-19 Critical Care Alliance (FLCCC). On November 3, TrialSite reported on the inclusion of the drug in the Alliance’s I-MASK+ protocol; the new manuscript comprehensively reviews the entirety of the emerging evidence from recent publications in journals, pre-print servers, and randomized trial results posted on clinicaltrials.gov. The FLCCC was created in March by Professor Paul Marik, MD, in order to continuously analyze the quickly-evolving science and clinical data for the purpose of creating COVID-19 treatment protocols. The corresponding author for the review is Pierre Kory, MD, MPA, an Associate Professor of Medicine at St. Luke’s Aurora Medical Center. 

While Other Drugs Have Failed, Ivermectin Studies are Now Showing Consistent and Substantial Benefits

The Alliance writes that, to date, much of the research being conducted and the care being given has been plagued by the use of medicines at, “inappropriate time points during this now well-described multi-phase disease.” And at this point, due to either trial design errors or lack of efficacy, negative study results including the SOLIDARITY trial have almost eliminated any role for remdesivir, hydroxychloroquine, lopinavir/ritonavir, interferon, convalescent plasma, tocilizumab, or monoclonal antibody therapy, especially in later phases of the disease. In the face of these failures, “the FLCCC recently discovered that ivermectin, an anti-parasitic medicine, has highly potent real-world, anti-viral, and anti-inflammatory properties against SARS-CoV-2 and COVID-19.” They reached this opinion via a review of a wide range of studies, including many randomized and observational studies. FLCCC found repeated and substantial improvements in outcomes when ivermectin is utilized both as a prophylactic and in treatment for mild, moderate, and even severe COVID-19 cases.  

Long List of Reasons

The FLCC expert panel reached consensus in advising that ivermectin should be “systematically and globally” used for both prevention and treatment of COVID-19 based on 11 factors, including: invitro studies over the past decade that show ivermectin slows or stops replication of many viruses, ivermectin inhibits SARS-CoV-2 replication in infected cell cultures, and it is a potent anti-inflammatory shown to inhibit cytokine production. The clinical data shows that it stops transmission in those exposed to patients with COVID-19, it quickens recovery and stops deterioration in those with mild to moderate disease who were treated early after symptoms, and it reduces ICU admission and death in hospitalized patients, even among those already critically ill. Finally, in several epidemiologic analyses, “striking reductions in case-fatality rates can be measured in regions with widespread use,” and it is proven safe with over billions of uses in history while being very low-cost.

Offering a compelling, comprehensive summary of evidence, scientific rational and a call to action, Dr. Pierre Kory recently participated in a Grand rounds, describing the accumulating case for ivermectin to the Associazone Naso Sano Provider ECM, a Rome-based international association of ENT physicians. 

NIH Says NO to Ivermectin; World Expert Urges Caution

Not everyone in the medical community agrees that ivermectin should be used widely, however the FLCCC recommendation relies on previously unavailable evidence. In its last ivermectin update from August 27, NIH’s COVID-19 Treatment Guidelines Panel recommended, “against the use of ivermectin for the treatment of COVID-19, except in a clinical trial.” They argue that pharmacokinetic and pharmacodynamic studies suggest that doses up to 100 times that approved for humans would be needed to be comparable to levels shown to have in vitro effects and that clinical data are limited. Also on August 27, MedPage Today weighed in on ivermectin. They cite Carlos Chaccour, MD, PhD of the Barcelona Institute for Global Health (ISGlobal), who studies ivermectin in the treatment of tropical diseases. “The pandemic creates a sense of urgency and we tend to cut some corners, and that can be okay, but you don’t cut all corners,” offered the doctor. “There needs to be scientific rigor. People may say, ‘What do you have to lose? It’s a safe drug,’ but no drug is free from side effects,” he said. The article notes that ivermectin can lead to GI side effects or skin rashes and that in rare cases it is neurotoxic; also, RCT’s are needed before wide use of ivermectin should be allowed.  

Dr. Chaccour presented on the TrialSite News Podcast and was generally approving of the TrialSite original documentary on the use of ivermectin in Peru.  

Since the last interviews and engagement with Chaccour, mounting evidence from both observational and randomized controlled studies pointing to the efficacy of ivermectin as some form of treatment for COVID-19 becomes ever harder to ignore.

Avoiding the Hydroxychloroquine Mistake

According to Matthew Spinelli, MD, of the University of California, San Francisco, the positive evidence, to the degree it is anecdotal, is “difficult to interpret given that most patients who are infected will get better on their own, and the clinical manifestations are so variable for COVID-19.” Another doctor urging caution is Zeno Bisoffi, MD, PhD, of the University of Verona, Italy. “There were some results from observational studies claiming that [hydroxychloroquine] worked, but in fact they were small studies with very heavy methodological flaws,” Bisoffi said. “Nevertheless, they were cited everywhere, so most clinicians around the world were using hydroxychloroquine with no evidence—-This is a mistake we want to avoid with ivermectin.

Q&A: Moral Hazard of Ivermectin; Low Cost Not a Factor

Turning back to ISGlobal and Dr. Chaccour, he penned a “Q&A” on ivermectin and COVID-19 on August 8. In it, he argues that the state of the evidence is “equipoise,” meaning that “there is a reasonable doubt of whether a drug might be of use or not. Testing of ivermectin against SARS-CoV-2 in clinical trials is warranted.” Key issues include the dose question as well as whether the drug might harm folks in proinflammatory states. Per Chaccour, “Given the absence of reasonable evidence that ivermectin has any efficacy against SARS-CoV-2, the risk-benefit analysis dictates that we should be prudent, i.e. evaluate the efficacy (and safety in this context) before taking ivermectin to the population level.” He also argues that there may be a “moral hazard” to ivermectin if people using it feel “safe” and quit using face masks, etc. Regarding whether big pharma may be wary of the low-cost of ivermectin, Chaccour argues that given the market size for a COVID-19 product, i.e. billions of people, adequate incentives exist for even a “cheap” drug.  

Dr. Chaccour makes an important point here:  a generic pharmaceutical company could potentially generate significant revenues based on a commercial, regulatory approved, version of ivermectin. There most certainly will be a large market for a low cost, widely available option targeting COVID-19 alongside vaccines and advanced therapies, such as monoclonal antibodies should they ultimately become proven safe and effective.

Is Ivermectin Too Good?

On balance, the arguments against thoughtful use of ivermectin outside of trials are unconvincing. The issue of whether a dangerous dose would be needed to fight COVID-19 is somewhat moot, in that many doctors around the world are using safe dose levels every day and seeing results. Moreover a number of studies have been completed, pointing to positive findings.  And the implication that this is an “all or nothing” situation is not quite true. In between the scenarios of  every COVID-19 patient  being given ivermectin and the other extreme of strictly limiting the drug to RCT’s, there is much room for a wide variety of clinical and research strategies. If some doctors use ivermectin and some don’t, this will provide ongoing data to inform us down the road. From TrialSite’s perspective, the FLCCC makes a rational argument. 

Why is ivermectin not being more widely studied and utilized? The most likely and most defensible reason is that it is due to the ignorance of the large and rapidly emerging amounts of recent data showing efficacy that was compiled by the FLCCC.   

Another possibility is that a major benefit, the drug’s cheapness, has inhibited the commercial ecosystem from honing in on this promising medicine. Although here, TrialSite suggests that a substantial market opportunity for a generics healthcare venture in fact does exist. Or perhaps just as troubling, research hubris–a kind of investigational elitism–could serve as a rampart against the accumulating evidence produced by universities and health systems in both low and middle-income countries (LMICs), as well as from the clinic in wealthy countries (such as the United States and Australia). That is, only an elite faction associated with national research agencies, regulators and top academic medical centers–and pharmaceutical companies, can produce the answer to the COVID-19 pandemic crisis. Regardless, it is tragic given the COVID-19 death toll to date. 

Call to Action: Make sure to read Dr. Kory’s latest manuscript.  Also view Dr. Kory’s Grand rounds to the Associazone Naso Sano Provider ECM. Send TrialSite your comments.

Responses

  1. I am confused by the NIH’s incorrect idea that you would need very high doing of ivermectin to get therapeutic benefit – this is clearly not true – ivermectin partitions really well to the lung and is stable there for more than 30 days in large animal studies. The false idea seems to come from serum measurements, which of course are not as relevant as lung. A UK group modelled conventional human dosing based on the animal data would give 10 times the required dose (peer-reviewed, published in good journal*) – how or why did NIH get this so wrong ?

    DAJ

    U. Arshad, H. Pertinez, H. Box, L. Tatham, R.K.R. Rajoli, P. Curley, M. Neary,
    J. Sharp, N.J. Liptrott, A. Valentijn, C. David, S.P. Rannard, P.M. O’Neill,
    G. Aljayyoussi, S.H. Pennington, S.A. Ward, A. Hill, D.J. Back, S.H. Khoo,
    P.G. Bray, G.A. Biagini, A. Owen, Prioritisation of anti-SARS-cov-2 drug
    repurposing opportunities based on plasma and target site concentrations
    derived from their established human pharmacokinetics, Clin. Pharmacol.
    Ther. (2020), https://doi.org/10.1002/cpt.1909.

  2. TSN has done a fantastic job following the evidence for Ivermectin and informing your viewers!

    Dr. Marik, Dr. Kory and the rest of the FLCCC Alliance are heroes in the Medical Industry! Researching, developing and educating the masses on outpatient treatment for Covid-19 is not their responsibility. These excellent CC physicians are dealing with massive caseloads of critically ill Covid-19 patients on a daily basis. In their “free” time they are performing the work that the NIH and FDA should be funding and spearheading. They were pioneers in the early realization and use of systemic steroids for critical Covid-19 patients. If only the WHO and the rest of the world would have listened hundreds of thousands of lives would have been saved. The world can’t let this happen again regarding outpatient therapeutics! Their clinical protocols must be disseminated immediately. Download the forward their I-MASK+ protocol to everyone you know. https://covid19criticalcare.com/wp-content/uploads/2020/11/FLCCC-IVERMECTIN-Protocol.pdf

    At first symptoms this protocol should be discussed with a patient’s primary care physician. If they are unwilling to treat the patient then use the list in the following link to select a doctor who is willing to treat outpatients: https://www.exstnc.com/

    Covid-19 is treatable but it’s critical to start treatment as soon as possible after symptom onset. This is a call to action for everyone to help get the word out!

  3. Please be aware that Dr. Chaccour’s “Q&A” was a blatant attempt and carefully worded work to discredit ivermectin.
    Why he is doing this is a mystery to me. The question arises…who paid him to write the “Q&A on ivermectin”?
    He does not say it doesn’t work… he says it mightn’t work.
    He attempts to say that people might use the veterinary drug which “might be dangerous”. Really ?
    He says it’s got “dangerous side effects”… no it hasn’t, it’s got far less than hydroxychloroquine or remdesivir.
    He attempts to say it hasn’t been approved by TGA or FDA etc. (Actually it has been approved by the Australian TGA… for other diseases and can, in Australia, be prescribed off-label)
    He says too you’d need too much dose-rate and kill the patient… untrue, ask Dr Borody or Dr. Marik who have a very effective triple-protocol sorted out… especially with zinc turbo-ing it.
    He says it needs trialling more for safety… hell, it’s been used over four billion times worldwide.
    It seems to protect whole populations prophylactically where they already use it for other diseases.
    He also tries to simplify a complex problem by stating that more needs to be done.
    You bet there is… and most of it by more professional people not bent by some other agenda.

    1. I agree on your observations regarding Dr. Chaccour’s comments. I’ve also been wondering why he’s been so conservative on the topic. Early on it made sense since the Monash in vitro study used extremely high concentrations that can’t be achieved in tissue. However, we’re so much further along now with sound, repeated clinical evidence of efficacy using very safe dosages. My guess is that he continues to be very cautious and overly conservative because he’s running an RCT and he was behind the curve on this subject. That’s not an excuse by any means but it’s just my opinion of what might explain his continued cautionary comments. Considering the very high safety margin of IVM, which he knows as well as anyone, it’s very disappointing to see his responses at this stage.

      1. The high concentration used in the Monash in vitro study has been a huge detriment to further investigation by Western medicine. Dr Wagstaff herself commented that the Vero cell line, while it expresses ACE2, does not express interferon alpha or beta. The most potent action of Ivermectin is the way it works in concert with the immune system and inhibits the SARS-CoV-2 virus ability to disable interferon pathways, something that the Vero cell monolayer cannot reproduce. The dose-too-high argument does not take these factors into account, and we see efficacy even with the standard safe 200mcg/kg doses.

        Here is the link for reference: https://www.reddit.com/r/ivermectin/comments/iks00x/ivermectin_docks_to_the_sarscov2_spike/g3oh18x/

      2. You are probably correct Paul Elkins… Dr. Chaccour was very much behind the times but as you explain, he’s running an RCT and wants the results to be news maybe.

        I’m no doctor but commonsense demands that an RCT is not required for ivermectin.

        Dr. David Scheim says it all here… BUT you have to be patient enough to want to know what it’s really about;

        https://www.youtube.com/watch?v=4h2nO4wMRis

        It is 35minutes or slightly more but absolutely revealing.

  4. Dr. Marik and the FLCCC Alliance are heroes in the Medical Industry! Researching, developing and educating the masses on outpatient treatment for Covid-19 is not their responsibility. These excellent CC physicians are dealing with massive caseloads of critically ill Covid-19 patients on a daily basis. In their “free” time they are performing the work that the NIH and FDA should be funding and spearheading. They were pioneers in the early realization and use of systemic steroids for critical Covid-19 patients. If only the WHO and the rest of the world would have listened hundreds of thousands of lives would have been saved. The world can’t let this happen again regarding outpatient therapeutics! Their clinical protocols must be disseminated immediately. Download the forward their I-MASK+ protocol to everyone you know. https://covid19criticalcare.com/wp-content/uploads/2020/11/FLCCC-IVERMECTIN-Protocol.pdf

    At first symptoms this protocol should be discussed with a patient’s primary care physician. If they are unwilling to treat the patient then use the list in the following link to select a doctor who is willing to treat outpatients: https://www.exstnc.com/

    Covid-19 is treatable but it’s critical to start treatment as soon as possible after symptom onset. This is a call to action for everyone to help get the word out!

  5. Me cago 10 veces en los expertos que niegan el uso de ivermectina. Mi hijo tomó dos dosis de 3mg. Y desaparecieron los sintomas. Siguio con amoxicilina y ácido clavulánico para la neumonía. Eso fue el 6 de abril del 2020.

  6. Me cago 10 veces en los expertos que niegan el uso de ivermectina. Mi hijo tomó dos dosis de 3mg. Y desaparecieron los sintomas. Siguio con amoxicilina y ácido clavulánico para la neumonía.