Gilead: Twenty-one billion reasons to discredit hydroxychloroquine (ORIGINAL ARTICLE)

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Authors
  • James M. Todaro, MD
Journal OmniJournal
Date July 23, 2020

Now primarily a marketing machine to sell drugs of dubious benefit, this industry uses its wealth and power to co-opt every institution that might stand in its way, including the U.S. Congress, the Food and Drug Administration, academic medical centers, and the medical profession itself.

- Marcia Angell, former editor-in-chief of the NEJM, The Truth About the Drug Companies

Introduction

In the history of medicine, no single drug has been so singularly attacked by the media, World Health Organization, government officials and institutional health experts as hydroxychloroquine. Approved as a “safe and cost-effective” essential medicine by the WHO, CDC and regulatory authorities across Europe, hydroxychloroquine has been prescribed to millions of patients over the past 65 years. Despite decades of known safety, hydroxychloroquine was labelled “dangerous” and a “poisonous substance” after showing promise as a therapeutic for COVID-19.

Many attribute this negative publicity to anti-Trump sentiment from mainstream media outlets including CNN, MSNBC, Washington Post, New York Times and Huffington Post. This thesis does not entirely hold up to scrutiny though. President Trump named both hydroxychloroquine and Gilead’s remdesivir as a “game changer” in his breaking March 19th press conference.

There are promising therapies produced by Gilead, and that’s remdesivir. Remdesivir. And that’s a drug used for other purposes that’s been out and has had very good results for other purposes, but it seems to have a very good result, having to do with this virus...So you have remdesivir and you have chloroquine and hydro- — hydroxychloroquine. So those are two that are out now, essentially approved for prescribed use. And I think it’s going to be very exciting. I think it could be a game changer...Very powerful. They’re very powerful.

- President Donald J. Trump, March 19th, 2020. 11:31 AM EDT [1]

At the time of the press conference, there was only in vitro evidence of remdesivir’s effectiveness against SARS-CoV-2. No clinical trial existed showing remdesivir to be effective. [2] The preliminary results from the NIH clinical trial were not available until over a month later on April 29. [3] The evidence of its efficacy primarily stemmed from a few in vitro studies that included an article published in the Nature-owned journal Cell Research. Interestingly, the Nature publication demonstrated that both remdesivir and chloroquine were effective against SARS-CoV-2, stating “remdesivir and chloroquine are highly effective in the control of 2019-nCoV infection in vitro.” [4] While there was only in vitro evidence of successes with remdesivir, there was both in vitro and clinical evidence of hydroxychloroquine’s efficacy. [5] Nevertheless, scientists, including Dr. Fauci, as well as the WHO and media outlets worldwide criticized Trump for providing false hope on the therapeutic effect of hydroxychloroquine while staying quiet about remdesivir.

The effort to undermine hydroxychloroquine appears to have begun months prior to Trump’s announcement. Chloroquine was first shown to have strong antiviral effects on SARS-CoV infection in primate cells back in the 2005 publication Chloroquine is a potent inhibitor of SARS coronavirus infection. [6] Pharmaceutical companies were likely aware that if hydroxychloroquine was shown to be effective against SARS-CoV-2 it would diminish the value of patented therapeutics or vaccines. Through lobbying efforts, regulation may have been the first step to control the availability of hydroxychloroquine.

This may have been what occurred in France. Hydroxychloroquine was available without prescription in France for years. This came to an end on January 13, 2020, when hydroxychloroquine was classified “in all its forms” as a “list II poisonous substance.” [7] After decades of widespread use, hydroxychloroquine quickly became a restricted substance in France in the earliest days of the COVID-19 pandemic. Just several weeks later, Dr. Didier Raoult in the South of France would report his landmark clinical trial demonstrating hydroxychloroquine’s efficacy against COVID-19. [5]

Why was hydroxychloroquine—a drug safely used for over half a century—aggressively labeled dangerous while a medication that proved ineffective for hepatitis C with an unknown safety profile got a pass? Herein I outline the evidence showing hydroxychloroquine to be a direct threat to Gilead’s success as well as the massive sphere of influence Gilead has over government taskforces, the World Health Organization, medical journals, academic institutions and research scientists. These organizations provided ammunition for the media’s war on doctors prescribing hydroxychloroquine.

Remdesivir vs hydroxychloroquine

Gilead’s stock rises and falls based on the successes and failures of both hydroxychloroquine and remdesivir. Immediately before Trump first announced hydroxychloroquine as a promising therapeutic for COVID-19, GILD traded at a local high of $85 per share, a price unattained since early 2018. Hours after Trump’s press conference, GILD dropped 8.7%, and then continued to plummet to $69 per share the following week—erasing $21 billion from its market cap in mere days. Immediately after Dr. Fauci announced the success of remdesivir in the NIH trial, GILD stock surged back to $85 per share. Compared to the largest pharmaceutical companies by revenue, Gilead has consistently outperformed in this pandemic with GILD gaining over 20% YTD while most of its competition struggled with losses or meager gains. This growth is almost certainly attributed to remdesivir’s promise as an effective treatment for COVID-19.

Gilead has a direct financial incentive for hydroxychloroquine to fail. Actually, based on its share price, Gilead has 21 billion reasons to discredit hydroxychloroquine. Perhaps no other company has more to gain in the immediate future from hydroxychloroquine’s failure than Gilead.

Medical journals

Medical journals have increasingly become marketing machines for big pharma. This has been openly stated by editors of even the highest impact medical journals. Back in 2003, Richard Horton, editor-in-chief of The Lancet wrote, "The business climate for most modern medical journals, whether in the for-profit or non-profit sector, is strongly pro-pharmaceutical industry…In this environment, I know that it can be difficult for editors to raise questions about the ethics and marketing tactics of pharmaceutical companies..." [8] The following year Horton again bemoaned the influence of big pharma stating, “Journals have devolved into information laundering operations for the pharmaceutical industry.” [9] Similarly, Marcia Angell, former editor of the New England Journal of Medicine, excoriated the industry in her book The Truth About the Drug Companies saying, "Now primarily a marketing machine to sell drugs of dubious benefit, this industry uses its wealth and power to co-opt every institution that might stand in its way, including the U.S. Congress, the Food and Drug Administration, academic medical centers, and the medical profession itself. (Most of its marketing efforts are focused on influencing doctors, since they must write the prescriptions.)" [10]

Although written in 2004, Marcia Angell’s comments are especially prescient in the current setting of the promotion of remdesivir over hydroxychloroquine. In marketing alone, the situation has only worsened over the past two decades. According to researchers at Dartmouth College, the US pharmaceutical industry increased total spending on marketing from $17.7 billion in 1997 to nearly $30 billion in 2016. The strategy was successful with US spending on prescription drugs ballooning from $117 billion to $329 billion during this time. [11] Advertising and sponsorships are a substantial source of revenue for most medical journals comprising up to 80% of publishing revenue for some journals. [12] Likely less publicly vocal today than over a decade ago due to growing control of big pharma, editors still secretly complain about the influence of big pharma. Just recently, Philippe Douste-Blazy, former French Minister of Health and Under-Secretary-General of the United Nations, reported a leaked conversation from a conference where editors-in-chief of both The Lancet and NEJM bemoaned big pharma’s control over publishing, “These meetings that are completely behind closed doors, only with experts. No one can record, no one is taking any pictures…but still, there was a meeting the other day of the directors of scientific journals like The Lancet, The New England Journal of Medicine…and it ended up leaked. The Lancet’s boss, Horton, said ‘Now we are not going to be able to, basically, if this continues publish any more clinical research data because the pharmaceutical companies are so financially powerful today and are able to use such methodologies, as to have us accept papers which are apparently methodologically perfect, but which, in reality, manage to conclude what they want to conclude.’”[13] The reality is that without advertising revenue, most medical journals would go bankrupt. The unfortunate downside is that the very survival of journals relies on keeping big pharma happy at the expense of scientific truths.

The Lancet may have chosen satisfying Gilead over scientific truths when it published a fraudulent study showing that hydroxychloroquine increased mortality and lethal arrythmias in COVID-19 patients.

On May 22, 2020, The Lancet published a peer-reviewed, observational study comparing hydroxychloroquine to standard therapy in 96,032 hospitalized COVID-19 patients. [14] Almost immediately afterwards, the WHO suspended all clinical trials on hydroxychloroquine because of safety concerns. [15] Dr. Fauci also commented on the dangers of hydroxychloroquine, telling CNN’s Jim Sciutto that it likely causes "adverse events with regard to cardiovascular." [16]

Independent researchers not beholden to big pharma quickly recognized the study to be predicated on a likely fraudulent dataset that included an impossible number of COVID-19 patients or deaths and an improbable number of partnerships with hospitals. Almost laughable if not for the gravity of the malfeasance, the dataset was provided by the unknown corporation Surgisphere with only five employees that included a science fiction writer and erotic model-for-hire posing as the Director of Sales. [17] Facing overwhelming evidence that the study was fraudulent, the authors retracted the study in less than two weeks from the date of publication. [18]

One could argue that the publication of this study was a mere oversight by The Lancet. That is, a study that slipped through the peer-review process. Let’s speculate for a moment, however, on what the strategy would be to publish a fraudulent study discrediting hydroxychloroquine.

Step 1. Establish plausible deniability by relying on an external corporation to provide the dataset. Surgisphere.

Step 2. Delete any digital footprint that could jeopardize the integrity of the data source. Surgisphere’s website is not included in the Internet Archives.

Step 3. Establish a track record of publications in high impact journals that would lend legitimacy to the Surgisphere dataset. The authors had just enough time to publish in NEJM the study Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19 using the Surgisphere dataset. (This study was later retracted as well.) [19]

Step 4. Select a lead author with impeccable credentials. Dr. Mandeep Mehra is a professor of medicine at Harvard Medical School, the William Harvey Distinguished Chair in Advanced Cardiovascular Medicine and the medical director of the Brigham Heart and Vascular Center in Boston. [20]

Step 5. Obfuscate the dataset as much as possible so that its integrity would be difficult to definitively invalidate. Patient data in The Lancet study was categorized by continent such that even the countries supposedly participating in the dataset were hidden.

Step 6. Publish the study in a prestigious medical journal with the comfort of knowing that it will immediately garner the support of the WHO, Dr. Fauci and influential scientists worldwide. The Lancet.

Despite all the above hypothetical steps, through the power of social media platforms such as Twitter, independent researchers were able to collaborate to quickly debunk the study.

The motivation for the above actions is admittedly still unclear. The connection between Gilead and the study authors is tenuous. What is known is that both Dr. Mehra and Dr. Sapan Desai (founder of Surgisphere) have openly praised remdesivir in various interviews and tweets. Of note though, Dr. Mehra was one of just a few experts selected to speak at a Gilead sponsored COVID-19 conference live-streamed by thousands of experts worldwide in early April. [21] Without a formal investigation into this affair, it is likely the motivation—be it attention seeking or the meddling of big pharma—will never be fully revealed.

The authors and Lancet were not the only involved parties though. The WHO suspended worldwide clinical trials on hydroxychloroquine based on this study.

World Health Organization

Gilead helps fund the WHO. Gilead Sciences provided 0.12% of the WHO’s funding for the biennium of 2018-19—more than doubling its contribution from the prior biennium. [22] This may seem like an insignificant percentage, but it’s important to note that China contributed just 0.21%, Italy 0.48% and Spain 0.06% of the WHO’s funding. With the exception of Sanofi, Gilead gave more to the WHO than any other pharmaceutical company. With remdesivir approved as a standard therapy for COVID-19, I suspect Gilead will further increase its contributions to become the largest pharmaceutical donor in the 2020-2021 biennium. While Gilead may appear philanthropic, one must wonder how ethical it is for organizations making global recommendations on therapeutics to receive substantial funding from big pharma.

This conflict of interest is suspicious considering the WHO’s dogged criticism of hydroxychloroquine while praising remdesivir. In late February 2020, WHO assistant director-general Bruce Aylward said: “There is only one drug right now that we think may have real efficacy and that’s remdesivir.” [23] This statement is peculiar because just two weeks prior on February 5, an article was published in Cell Research titled “Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV).” [4] Despite only in vitro evidence of efficacy for both medications, remdesivir was touted as a potential therapeutic while hydroxychloroquine and chloroquine were completely disregarded. It was only after grassroots investigators James Todaro, MD and Gregory Rigano published an article on chloroquine/hydroxychloroquine as a treatment for COVID-19 that caught the attention Elon Musk and President Trump did the WHO begin clinical exploration of hydroxychloroquine. [24]

Through various actions and inactions, the WHO provided little support for clinical trials on hydroxychloroquine. The WHO did nothing to dispel the myth that hydroxychloroquine was dangerous throughout April and May. We now know that the WHO was collaborating with Oxford University researchers, who were giving patients doses of hydroxychloroquine exceeding four times that of treatment courses administered by Drs. Raoult and Zelenko. [25] Surely if hydroxychloroquine was dangerous, these high doses would not have been administered with the WHO’s blessing. Nevertheless, the WHO remained quiet allowing the narrative of hydroxychloroquine’s harmful effects to grow resulting in diminishing enrollment in clinical trials.

Inaction turned into action when the WHO aggressively suspended its clinical trials of hydroxychloroquine in May 2020, after The Lancet published its fraudulent observational study. This bombshell announcement was splashed across media headlines reaching millions of patients and healthcare providers alike and deterring not just enrollment in its own SOLIDARITY trial, but also clinical trials outside the purview of the WHO. The WHO made this decision without any independent assessment of the study’s veracity. Soumya Swaminathan, chief scientist for the WHO, openly admitted the WHO’s mistake by stating, “It is [very] difficult for us to check data quality of each published paper & we trust authors to adhere to basic [standards]. HCQ restarted today after data safety committee approval.” [26] It’s very surprising that an organization such as the WHO employing over 7000 people and receiving over $2 billion annually to investigate potential therapeutics for COVID-19 issued guidance based on a study that unpaid independent researchers debunked just a few days later.

US Government

The pharmaceuticals and health products spent $295 million in lobbying efforts in the United States which places it in 1st place in money spent on lobbying. For comparison, the insurance industry and automotive industry only spent $155 million and $69 million in 2019, respectively. [27] In 2019, Gilead spent nearly $6 million in political lobbying efforts. This number is on track to reach record highs in 2020 as Gilead has spent already nearly $2.5 million on lobbying in just Q1 of 2020. [28] The money appears to be well spent. The exclusive NIH COVID-19 Treatment Guidelines Panel that informs US clinicians how to care for patients is occupied by 8-9 experts who have received financial support from Gilead. [29]

Academic medical centers and scientists

To compile all of the thousands of scientists and research institutions who have received funding from Gilead would take weeks of effort. However, it is noteworthy that some of the most vehement critics of hydroxychloroquine have conflicts of interest with Gilead. Just for example, in the New York Times feature He Was a Science Star. Then He Promoted a Questionable Cure for Covid-19, [30] all three scientists (Karine Lacombe, Christine Rouzioux, and Jean-Michel Molina) criticizing Dr. Raoult and his study are either on Gilead's advisory board and/or received funding from Gilead. [31] [32] [33] Notably, the New York Times article fails to mention these conflicts of interest.

Some other notable examples include Stanford University School of Medicine that conducted two clinical trials on remdesivir (one funded by the NIH and the other by Gilead); University of Alabama at Birmingham who received funding from the NIAID to develop remdesivir (of note, Dr. Richard Whitley, principal investigator of the $37.5 million dollar NIAID grant, is on the board of directors for Gilead).

Conclusion

Gilead’s influence over the process of clinical investigation and approval of therapeutics is undeniable. A direct threat to remdesivir, hydroxychloroquine has likely been in Gilead’s crosshairs for months.

References

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  5. 5.0 5.1 Gautret, P; Lagier, JC; Parola, P et al. (20 March 2020). "Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial". International Journal of Antimicrobial Agents. Retrieved 21 July 2020.
  6. Vincent, MJ; Bergeron, E; Benjannet, S et al. (22 Aug 2005). "Chloroquine is a potent inhibitor of SARS coronavirus infection and spread". Virology Journal. Retrieved 21 July 2020.
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  14. Mehra, MR; Desai, SS; Ruschitzka, F; Patel, AN (May 2020). Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis. Lancet. doi:10.1016/S0140-6736(20)31180-6. PMC 7255293. PMID 32450107.
  15. Guardian. (25 May 2020). "WHO halts hydroxychloroquine trial for coronavirus amid safety fears". Guardian. Retrieved 21 July 2020.
  16. Dr. Anthony Fauci. (27 May 2020). "Fauci: Science shows hydroxychloroquine is not effective as a coronavirus treatment". CNN. Retrieved 21 July 2020.
  17. Todaro, James (29 May 2020). "A Study Out of Thin Air". MedicineUncensored. Retrieved 21 July 2020. .
  18. Mehra, MR; Ruschitzka, F; Patel, AN (June 2020). Retraction—Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis. Lancet. Retrieved 21 July 2020.
  19. Mehra, MR; Desaid, SS; Kuy, S et al. (25 June 2020). "Retraction: Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19. N Engl J Med. DOI: 10.1056/NEJMoa2007621.". NEJM. Retrieved 21 July 2020.
  20. " Mandeep R. Mehra, MBBS, FACC Professional Bio ". ACC. Retrieved 21 July 2020.
  21. Redaccion Medica (6 April 2020). "Coronavirus: Gilead and Seimc train more than 8,000 professionals". Asscat Hepatitis. Retrieved 21 July 2020.
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  26. Soumya Swaminathan (4 June 2020). "We acted in the safety interests of patients in the trial, relying on the advice of our steering comm. It is v difficult for us to check data quality of each published paper & we trust authors to adhere to basic stds. HCQ restarted today after data safety committee approval". (Tweet) via Twitter
  27. Erin Duffin (4 March 2020). "Leading lobbying industries in the United States in 2019, by total lobbying spending". Statista. Retrieved 21 July 2020.
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  29. NIH (11 June 2020). "Appendix A, Table 2. COVID-19 Treatment Guidelines Panel Financial Disclosure for Companies Related to COVID-19 Treatment or Diagnostics". NIH. Retrieved 21 July 2020.
  30. Scott Sayare (12 May 2020). "He Was a Science Star. Then He Promoted a Questionable Cure for Covid-19.". New York Times. Retrieved 21 July 2020.
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  32. Cheret, A; Nembot, G; Melard, A et al. (April 2015). " Intensive five-drug antiretroviral therapy regimen versus standard triple-drug therapy during primary HIV-1 infection (OPTIPRIM-ANRS 147): a randomised, open-label, phase 3 trial". The Lancet Infectious Diseases. Retrieved 21 July 2020.
  33. Balde, A; Lang, S; Wagner, A et al. (16 Jan 2019). "Trends in the risk of myocardial infarction among HIV-1-infected individuals relative to the general population in France: Impact of gender and immune status". PLOS ONE. Retrieved 21 July 2020.

Peer Review

Gilead: Twenty-one billion reasons to discredit hydroxychloroquine peer review