The World Health Organization (WHO) held a media briefing including Dr. Maria Van Kerkhove and Dr. Soumya Swaminathan to discuss the potential of ivermectin as a generic drug, demonstrating some promise as a treatment for at least mild, early-onset COVID-19. Dr. Van Kerkhove, a technical lead of this global organization’s COVID-19 response and expert in emerging diseases and zoonosis, reported that she is carefully monitoring clinical trials and noted that some of these studies, soon to conclude, may trigger WHO to carefully review, analyze and describe a recommendation in the weeks to come.
Dr. Van Kerkhove shared that they currently have data on 1,500 study patients from 11 studies but that ultimately, there could be data involving up to 7,000 patients from a total of 56 studies. Emphasizing that the underlying studies vary in quality, WHO factors that element into their ultimate recommendations. A WHO steering committee will carefully look at the updated data to consider any change in guidance. Van Kerkhove shared that this process is, in fact, expedited; however, she emphasized the incredibly comprehensive review that will ultimately be shared with the public.
TrialSite notes the WHO meta-analysis appears to differ from that of the Front Line Critical Care Alliance (FLCCC) and associated recommendations. This American-based group incorporates more of the ivermectin studies, as did initially, Dr. Andrew Hill, affiliated with University of Liverpool as well as Unitaid, a group that operates within the WHO. Hill has been an active proponent of investigating ivermectin based on the numerous clinical trial results covered in his meta-analysis. Another meta-analysis that attracts less attention, but could actually represent the most comprehensive of them all, is the work product from Dr. Tess Lawrie.
Ivermectin not Prioritized in the Solidarity Trial
WHO’s Dr. Soumya Swaminathan, Director-general of the Council of Medical Research, India, also introduced herself, starting off by saying that the low-cost, economical drug showing promise wasn’t prioritized in the Solidarity trial to date.
Now, she shared that an expert WHO committee is reviewing recommendations for this global clinical trial (the same one that found remdesivir not to be effective) and went on to talk about their comprehensive guidelines process—e.g., “…tracking all developments in the treatment, of COVID-19, the clinical trials that are going on all over the world, and we do living updates of meta-analysis…” Swaminathan described how each new trial, depending on the results of the data, can add (or not) to the evidence of a drug such as ivermectin. Ultimately, the decision is made by the “Guideline Development Group,” reports Dr. Swaminathan.
Swaminathan noted that currently, the group is looking at IL-6 inhibitors, heparin-like antithrombotic agents as well as ivermectin in the next couple of weeks, and a few other drugs. She emphasized the challenge of numerous small trials, which have the potential to show misleading results. WHO’s Director-general position is that they don’t want to make a decision that’s not scientifically valid. TrialSite notes that the WHO antithrombotic review is thanks to recently announced NIH-sponsored study results from ACTIV-4.
WHO Guideline Development Group
Who is in the WHO Guideline development group? This is the group that advised against remdesivir, based on Solidarity trial results published in the BMJ. The WHO “COVID-19 resources and guidance” page includes a link to the “COVID-19 Clinical Guidance.”
Interestingly, the document titled “COVID-19 WHO Guideline Development Group for Clinical Management of COVID-19 V3” was last updated May 2020—9 months ago, which seems like an eternity during a pandemic. For more up-to-date actions, they declare in the document to “see the website.”
In the most updated version of the guidelines, in regard to the management of “Mild COVID-19,” they share, “we recommend patients with mild COVID-19 be given symptomatic treatment such as antipyretics for fever and pain, adequate nutrition and appropriate rehydration.” The most common “antipyretics” in the USA, for example, are ibuprofen and aspirin.
Find Early Treatments: Reduce Disease Progression
The challenge here is that a growing number of doctors, researchers, and other professionals that focus on early-onset COVID-19 care have been crying out for more intensive study into possible treatments for early-onset treatment. That is treat the infection early even with mild symptoms to reduce the number that experiences disease progression in the first place.
TrialSite sums up the remdesivir story in “Not a knockout, drug but knocking it out of the ballpark,” as Gilead, from the perspective of a case study for an MBA student, demonstrated pure mastery of the business of drug development in pandemic conditions.
Remdesivir, as it turned out, unfortunately, wasn’t suitable for early-stage treatment, at least not in the current form of administration and cost. Gilead is looking into an oral dosage approach that would help (although WHO doesn’t accept ACTT-1 trial findings). But Gilead would need to lower its prices should it ever produce approved product for wide-spread, early onset use.
Remdesivir is the only FDA-approved drug in the U.S. specifically for COVID-19. From a financial standpoint, Gilead hit a home run with remdesivir, generating up to $2.7 billion in just several months. $1.9 billion worth of remdesivir was sold in Q4 alone.
Favipiravir is used in many countries, and in fact, is registered for use in Russia, India, and others for example although the true efficacy is still in question. The inclusion of Favipiravir in the WHO Solidarity trial was obviously a topic of interest, as back in October, the global health organization published a document titled “WHO R&D Blueprint COVID-19: informal consultation on the potential conclusion of Favipiravir in a clinical trial.” The “Working Group Member” chaired by Marco Cavaleri with the European Medicines Agency (EMA) suggested insufficient data for inclusion in the solidarity trial at that point.
Of course, proponents of ivermectin scream loudest for this particular type of case, and that’s exactly why regional health authorities in places such as certain states or municipalities in Brazil or India (e.g., Uttar Pradesh) embraced the generic drug for exactly that purpose. Some epidemiological data points to a positive association, but these types of reports haven’t been accepted by official health authorities or prominent non-governmental organizations.
Interestingly, although global health authorities and apex research bodies have all but left Hydroxychloroquine, the anti-malarial drug was embraced in the recent ANTICOV trial to test low-cost drugs for early-onset COVID-19 in developing nations that may not have sufficient access to vaccines.
On the pharmaceutical front, companies are working on designing antibodies and other powerful drugs to help with various stages of treatment–early treatment. Both Regeneron and Lilly’s monoclonal antibody products have evidenced that these investigational products, authorized for emergency use, can help, but they A) are difficult to administer in the context of early-onset care (e.g., ambulatory or home care use); B) are costly, although the government may subsidize the cost to the patient the provider may not defer costs associated with administration of care and C) they are authorized for those facing greater risk for hospitalization or disease progression. A UVA recently verified that Regeneron’s powerful monoclonal cocktail combination REGN-COV shows significant promise to help combat COVID-19.
AstraZeneca is developing a promising investigational product (AZD7442) originating out of Vanderbilt, including use for pre-exposure prophylaxis (PrEP), and Merck has at least two drugs (EID-2801 and MK-7110) in their pipeline (one developed via a university relationship the other acquisition) that could possibly have the potential for easy use in the future. GSK/VIR are also co-developing a drug known as VIR-7831/GSK4182136.
NIH Position on Ivermectin
Early in the New Year, members of the National Institutes of Health COVID-19 Treatment Guidelines panel met with the FLCCC along with Dr. Andrew Hill to learn more about their findings to date. Just several days later, this apex research body updated their recommendations. Although many proponents of ivermectin were disappointed (the NIH changed its recommendation from “recommend against except for research” to a new position that there is still insufficient data to recommend for, but now they also do not recommend against either. This is the change, but the apex body is consistent that additional “…Results from adequately powered, well-designed, and well-conducted clinical trials are needed to provide more specific, evidence-based guidance on the role of ivermectin for the treatment of COVID-19.” Interestingly, however, the NIH still hasn’t updated its actual rating page.