Gilead is a great American company, and it’s a great global company. Its drugs have had substantial impact on people’s lives. Compared to what was a death sentence a couple decades ago, now those with HIV and even AIDS can live a normal life. Gilead’s HIV/AIDS drugs have brought in a lot of money such as Genvoya, Truvada, Odefsey, and others. With nearly $23 billion in sales, its takes home nearly $7 billion in profits. Its market capitalization, at a share price of $74.57 per share, is nearly $94.7 billion. Sitting on $21 billion in cash, it must continue to develop and innovate in the world R&D market. The company is not a stranger to controversy. In fact, most recently the Donald Trump White House and Gilead locked horns over a patent that the government argues should be its intellectual property. With nearly 12,000 employees at their San Francisco Peninsula headquarters, the company generates a lot of wealth for the region and beyond along with saving a lot of lives.
The Wuhan Pandemic
An extremely dangerous virus emerged in Wuhan, China, toward the end of 2019 and took the name SARS-CoV-2, the virus behind COVID-19. As TrialSite News has disclosed, the Chinese government likely knew about the novel coronavirus contagion starting in November, if not even earlier. Under this theory, China commenced a systematic, comprehensive and some would argue, repressive campaign to contain the pathogen internally, while playing naive externally. Hence why so many infected people were able to fly out of the country to Europe, the U.S. and elsewhere. By December, U.S. intelligence sources were directing information to the White House, but not much action occurred in response at that point in time. Paranoia was still high that the “Deep State” was out to get the controversial president. That remdesivir was identified as a possible candidate treatment against the new and terrifying SARS-CoV-2 was apparent when the Wuhan Institute of Virology apparently attempted to file a patent covering remdesivir in China.
Early Research that Points to Remdesivir Potential
In early January, Gilead got right to work testing remdesivir against the novel coronavirus, as they had records revealing that the drug may be active against severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) in animal models. As those were comparable, it made sense to commence an intense and systematic study of this investigational treatment against the novel coronavirus. By January 31, China and Gilead announced they would test the investigational Ebola drug on the novel coronavirus.
Negative Data Points
Randomized controlled trials were not going well for remdesivir as the pandemic spread and horrifically intensified. For example, as the pandemic spun out of control during the period between February and March, a clinical trial in China investigating remdesivir led to the conclusion that the antiviral was not effective in reducing the time for improvement from COVID-19 or in helping to reduce mortality. Additionally, patients experienced a number of adverse events requiring Chinese research sponsors and investigators to terminate the remdesivir clinical trials.
In these studies, 237 patients were enrolled and randomly assigned to a treatment group (158 to remdesivir and 79 to placebo). Remdesivir use led to no material clinical improvement. However, patients receiving remdesivir had a faster time to clinical improvement than those receiving placebo, among patients with symptom duration of 10 days or less. Interestingly, adverse events were reported in 102 (66%) of the remdesivir recipients versus 50 (64%) of 78 placebo residents. The study team halted the remdesivir study early.
Out of Favor in the East, but Rises in the West
There was an exact correlation with the fall of remdesivir in the East and the rise in the West. That remdesivir became a popular investigational candidate targeting COVID-19 was an understatement, despite the failings in China. By March 18, the World Health Organization (WHO) launched a clinical trial that included remdesivir treatment. And more studies commenced. Also, lots of excitement existed around hydroxychloroquine, but it seemed as soon as Trump promoted the drug, it actually never received its fair chance.
The Controversial Trial Moves
The U.S. National Institutes of Health led an international, multi-center, placebo controlled double-blind randomized controlled study, and preliminary data suggested that remdesivir is effective in reducing the COVID-19 recovery time from 15 to 11 days in people with hospitalized COVID-19. Dr. Anthony Fauci’s National Institute of Allergy and Infectious Diseases (NIAID) sponsored this critical study that made a controversial decision to change the primary endpoint measures just weeks before the conclusion of the study. So today, the primary endpoint reads, “Time to recovery.” NIAID arguably “changed the goalpost.”
They had their rational for this, but nonetheless this study was the basis for Emergency Use Authorization (and soon a European approval). Although a few days in reduction of sick time is something, studies of Avigan (favipiravir) appear to do better. For that matter, observational studies of Ivermectin possibly do twice as good, such as in an observational study in Broward County Health where it actually reduced mortality. This is a measure that Remdesivir was originally supposed to meet. In at least two completed studies in Bangladesh, the anti-parasite drug performed arguably better than remdesivir. Regardless, by April 29th the ACTT trial results led to the NIAID announcing that remdesivir was superior to a placebo in reducing time to recovery for people hospitalized with advanced COVID-19 with lung involvement.
New England Journal of Medicine Position
The study results were published in the New England Journal of Medicine nearly a month later. Although NIAID, under Doctor Fauci’s direct watch, moved the goalpost of the study (again a controversial move) the study results posited in NEJM that “given high mortality despite use of remdesivir, it is clear that treatment with an antiviral drug alone is not likely to be sufficient.” Since deaths occurred while patients with COVID-19 were on remdesivir doses, the authors were arguably both deceptive and clear:
“However, given high mortality despite the use of remdesivir, it is clear that treatment with an antiviral drug alone is not likely to be sufficient. Future strategies should evaluate antiviral agents in combination with other therapeutic approaches or combinations of antiviral agents to continue to improve patient outcomes in COVID- 19.”
It was odd that the authors didn’t single out remdesivir, but included “all” antivirals. Perhaps evidence of the pharma-complex that TrialSite News suspects operates as a “system” at work? Even though a Chinese study published in The Lancet at the same time showed lackluster results with remdesivir, the University of Edinburgh Medical School’s John David Norrie came to the rescue by ridiculing said Chinese critique as “underpowered due to a lack of significant results” and an insufficient basis for any conclusions as the study was ended early.
Remdesivir Gets a U.S. Government Pass: Great Viral Marketing
Because the most powerful federal government in the world (e.g. Dr. Fauci and NIAID and the FDA) made its case, remdesivir was the drug of choice now despite the facts that it did nothing to help mortality rates, study goal posts were changed, and Chinese studies were questioning any value.
But there were a few days of sick time reduced, and NIAID agreed that something was better than nothing. Hence, moving forward all placebo patients in the ACTT Trial would receive remdesivir, and a great shift from “investigational” to “accepted” occurred.
Gilead couldn’t have asked for a better outcome given the questionable performance of the drug. The marketing brand was given the greenlight, and a powerful one at that with worldwide implications.
By April 2020, many in the government—industry—academia circles were hot on remdesivir as the most promising COVID-19 treatment.
The World Health Organization (WHO Solidarity Trial) included the antiviral drug as one of four major investigational treatments, as did the European Discovery Trial. And why not? It was given the full green light by the U.S. Government. By May 1, the FDA issued an Emergency Use Authorization for remdesivir for hospitalized COVID-19 patients, stating that it is “reasonable to believe” that known and potential benefits of remdesivir outweigh its known and potential risks, in some targeted populations hospitalized with severe COVID-19. Yet the government’s argument seemed just as much tautology as truth to some critically minded thinkers. As of May, there was absolutely no evidence that remdesivir reduced mortality in patients with COVID-19 in any way, as examined by researchers from the University of Oxford and The Centre for Evidence-based Medicine.
And Europe Follows the Leader
European and American drug development culture intertwine and interlock in a myriad of complex ways. Many multinational companies have subsidies in one or the other continent; the researchers and executives work together, attend the same conferences and regulators frequently converse and talk and parties from both continents sit on industry standards and harmonization committees. Of course, with the Trump election the traditional political ties were considerably strained at least in some regards, and in fact, vaccine nationalistic urges increasingly manifested in various press releases of various countries.
Yet, by April 2020, the European Medicines Agency (EMA) conducted a ‘rolling review’’ on remdesivir data. By April 3, a compassionate use review progressed with greenlight for compassionate use in Europe.
By early June, the European Committee for Medicinal products for Human Use (CHMP) commenced evaluation of remdesivir in earnest for a conditional marketing authorization after Gilead submitted the application.
As June 25 arrived, Europe followed the NIAID and FDA lead granting conditional marketing authorization for remdesivir, as a treatment of SARS-CoV-2 in adults and adolescents from 12 years of age with pneumonia who require supplemental oxygen. The Europeans appeared to box the parameters in a little more than the traditional allies on the other side of the Pond.
What is the main reasons Europe followed along? Well, in their own words, “The assessment of the dossier has now concluded with today’s recommendation,” which is mainly based on data from study NIAID-ACTT-1 sponsored by the U.S. National Institute of Allergy and Infectious Diseases (NIAID), plus supporting data from other studies on remdesivir. In Europe, the brand name would be Veklury.
India, Pakistan and Elsewhere
In India, the Hindustan Times were turning into promoters for remdesivir. As it turned out, the news organization is owned by the Bhartia family of industrialists. The Bhartia clan also happens to own Jubilant Life Sciences, which conveniently just secured a license from Gilead to manufacture and distribute remdesivir to 127 middle-and-low-middle nations, including India.
That the wealthy family would leverage various assets and holdings to cross promote assets isn’t too much of a surprise: its just the overt and obvious scale of the operation, including some of the claims in various Indian media outlets, that could shock some seeking at least the perception of commercial constraint.
As was discussed in critical publication News Laundry, it appeared that press owned by Bharti declared all things wonderful and possible about the drug while a more critical point of view states the drug was represented by “one disappointing clinical trial after another.”
Gilead leveraged the U.S. NIAID-driven “approval” thanks to that last minute goal post move approved by Fauci, secured acceptance in Europe and embarked on an intense deal making run in India in a Third World monetization push leading to deals with Dr. Reddy’s Labs, Cipla Ltd., Hetero Labs, Ltd., and Mylan. In Egypt, Gilead inked a remdesivir deal with Eva Pharma, while in Pakistan they licensed the manufacturing rights to Ferozsons.
By April, as regulatory approval was feeling imminent, Gilead committed its 1.5 million (what it estimated to be 140,000 treatment courses for patients) at no cost. As of this writing, the U.S. has 2.6 million cases alone with 128,437 deaths. And with remdesivir, the only approved drug for COVID-19 in the U.S. (again despite the fact the drugs like favipiravir are generic and approved in Russia, China and India—and the U.S. DOD invested $138+ million into that drug for a coronavirus like pandemic condition), the current donations by Gilead cover less than 10% of U.S. cases hence there will be ample room and time for monetization of remdesivir.
And time seemed to be on Gilead’s side because no competition could breakthrough thus far: that favipiravir was doing very well with approvals in major countries (Russia, China and India) got no real press in America; the hydroxychloroquine mishaps were unfortunate as the drug did show some potential if administered at the early stages and to the right patients but all vacated hope when Trump called it a “Game Changer.”
The Ivermectin story will take time to gain momentum in American and European demographics (if ever). But in the meantime, the “complex” of industry, government and academic interests show no intellectual curiosity whatsoever.
Hence, a certain protective zone has been established for Gilead monetization if it plays its cards right. According to the Kaiser Family Foundation (KFF), by June 10 the company still had not set the drug price or made it commercially available. As a large amount of severe to critical cases of COVID-19 remain older adults (now more young people are now getting infected in the South and West), there is both optimism about the drug’s possible benefits and concern about the price tag should it go high. The argument goes that the fiscal health of hospitals and the Medicare program itself could be at risk. Remdesivir would fall under Part A of Medicare, which pays for inpatient care because the drug was administered on an inpatient basis in clinical trials.
The ICER Estimates
The Institute for Clinical and Economic Review (ICER) is an independent drug pricing group not always loved by drug companies nor their lobbyists. KFF reports the ballpark pricing estimates from ICER range from $10 (cost of production) to around $4,500 per treatment, a price established to capture the value of the drug’s clinical improvements. Recently, ICER slightly updated the fights higher.
Prior to Gilead declaring a price, they stated it will not charge as much as $30,000 or $40,000. Frankly not that comforting, knowing Gilead’s aggressive business DNA. It will be difficult for health systems to purchase in bulk discount because there aren’t any real competing products on the market. Again, in India, Russia and China, generic favipiravir has been approved and it would appear in studies it performs comparably well if not better than remdesivir.
The Diagnosis Related Group (DRG) that CMS has told hospitals to use for COVID-19 patients reimburses at about $16,000 on average post a provisional 20% increase in inpatient reimbursement for COVID-19. For the average severely ill patient required to be on a ventilator for over four days, the reimbursement average comes out to $48,000, reports KFF.
Does the Recent Dexamethasone News Impact?
As TrialSite News recently reported, the University of Oxford was able to showcase the successful use of low-cost dexamethasone in a significantly sized COVID-19 clinical trial could impact the remdesivir price. Why? Well, if a low cost steroid can save a life, that is something that remdesivir cannot do. Hence, if the benefits of the study are proven as evidence in a peer-reviewed journal and therefore qualify it as the standard of care then remdesivir could be cut down to around $2,520 to $2,800, reported ICER.
Gilead Names it Price!
Well, just as of this writing, Gilead established a price point. Developed world public payers, such as U.S. Medicaid and the Department of Veterans Affairs, will pay $2,340 per treatment for a five-day course. Private insurers pay 33% more at $3,120 while developing world buyers secure discounts via deals Gilead inked with generic producers. Even at the now declared $2,340 price per treatment for public sector and $3,120 for private sector payers, about 10% of the existing market could represent remdesivir sales targets in the United States approaching $1 billion. Factor in sales in Europe and monetization in India and all the other countries, Gilead is doing deals in. Gilead is looking at far over $1+ billion per year while this nasty pathogen hangs around. Assuming competition is at bay.
CEO Daniel O’Day reported to STAT, “At this price its significantly below the value it brings to patients and to society. There is no doubt of that in my mind.” Well, there is doubt in the TrialSite Network! Frankly, Mr. O’Day can’t be picked on here. He is simply trying to do his job to drive shareholder value up. And to his credit, he kept the pricing to the lower end of the ICER suggested pricing spectrum. Gilead is behaving actually very well. The faults go with what is the “complex” or system of interests that systematically impedes competition and hence reduces choice, and demand and supply dynamics. And frankly with a population that for the most part doesn’t want to bother with topics as dull and tedious as drug choice and pricing.
Some Competition & Health Relief Best Come Soon
Americans are in for trouble. They don’t currently have a health care system that ensures the vast majority of people remain solvent. For example, in Seattle, one man’s fight with COVID-19 in the hospitals cost him $1.1 million. In New York, Janet Mendez started receiving a lot of bills from Mount Sinai Morningside hospital where she nearly lost her life to COVID-19. She now is buried with a price tag of $401,885.57. Grace Thomas in Denver, Colorado, also escaped with her life but now bills accumulate. Article after article warned prospective COVID-19 patients that if you do not have health insurance than you may owe at least $70,000 if not more.
Well there are a lot of people with no health insurance, in fact as much as 44 million in America. Assume 5% of them become ill and need some form of hospitalization say at $50,000, and we are looking at staggering numbers of debt here.
Remdesivir will fit into this business milieu. And if it couldn’t get any more timely for many normal folks, the Trump administration sought recently to strike down the rest of the ACA, meaning up to 20 million more Americans would lose health insurance. Keeping politics aside, as this author is by no means in agreement with the ACA, why this move would happen in the midst of pandemic this author can’t be sure? So to wrap all this up, TrialSite News cannot over emphasize enough the importance of true competition for COVID-19 treatments. This will help reduce financial burden during this historically unprecedented time of crisis.