The consumer advocate organizations such as Public Citizen recently sent a letter to the CEO of biopharmaceutical company Gilead, as well as the nation’s top regulators urging strong collaboration to develop a drug similar to the well-known Remdesivir. While the patent for Remdesivir dated to 2014, the Gilead’s patent for GS-441524 goes back to 2009, five years earlier. Remdesivir is the only therapy in the United States that has emergency authorization targeting COVID-19; the cost hovers at $2,340 per patient for a five-day course of treatment. TrialSite reported that according to some analysts, Gilead is expecting anywhere from $1 billion up to $3 billion for its first year since the FDA decision for emergency use. But why is Public Citizen and other groups writing letters and evangelizing for GS-441524? What is this drug?
Could Gilead be preventing access to a drug that could potentially help hundreds of thousands if not millions of Americans (and others around the world) better fight COVID-19? It is their drug, their patent, and their intellectual property; what gets in the way? Could there be benefits to Gilead by going against the herd? By taking a wildly contrarian, and some could label “transcendentalist” stand behaving completely different that is expected and hence influencing the march of history?
What is GS-441524?
This antiviral drug, developed by Gilead, is described as the main plasma metabolite of the antiviral product remdesivir, which has a half-life of about 24 hours in humans. As defined in Wikipedia, the nucleoside of GS-441524 is phosphorylated. By nucleoside kinases, and then phosphorylated again by nucleoside-diphosphate kinase (NDK) to the active nucleotide triphosphate form.
Known as the “black-market drug from China,” the drug is based on research from University of California, Davis, according to an article The Atlantic. Both Remdesivir and GS-441524 were tested against feline infectious peritonitis (FIP), a lethal coronavirus disease impacting domestic cats, and widely used despite no U.S. Food and Drug Administration (FDA) approval due to Gilead’s actual refusal to license the drug for veterinary use. At least one study has revealed that GS-441524 is comparable or perhaps even more powerful than remdesivir against SARS-CoV-2 in a cell culture.
In fact, a pair of researchers out of MD Anderson posit that GS-441524 is possibly superior to remdesivir for the treatment of COVID-19.
An MD Anderson pair, Victoria Yan, a Graduate Research Assistant at MD Anderson, wrote a paper with colleague Florian Muller, PhD, Department of Cancer Systems, Imaging, suggested in their findings that “While remdesivir has garnered much hope for its moderate anti-COVID-19 effects, its parent nucleoside GS-441524, has been overlooked. Pharmacokinetic analysis of remdesivir evidences premature serum hydrolysis to GS-441524; GS-441524 is the predominant metabolite reaching the lungs. With its synthetic simplicity and in vivo efficacy in the veterinary setting” they came outright and declared “GS-441524 is superior to remdesivir for COVID-19 treatment.”
Why doesn’t Gilead License the Product?
In May writing for The Atlantic, Sarah Zhang confirmed that Gilead invented and patented GS-441524 and collaborated with UC Davis early on to study the investigational products effectiveness against FIP. Ms. Zhang outright declares in The Atlantic that the company will not license this early-stage, investigational therapy. But why on earth not? Apparently, if Zhang is correct, because of Gilead’s concern that due to similarities to remdesivir, the FDA approval process could have been put in jeopardy. Originally developed for Ebola, remdesivir didn’t work out but with the onset of COVID-19, Gilead made some “small and clever modification that makes it better at entering cells, but it and GS-441524 work in exactly the same way to inhibit viruses.
The Public Citizen Position
The Washington DC-based nonprofit group now advocates for the release of the drug into the clinical research domain or if there exists some compelling reason not to than “publicly provide evidence why it is not scientifically or medically feasible to develop this drug in parallel with this close analogue, remdesivir.” As the pandemic rages—approaching 5 million cases and presently 160,323 deaths as of this writing, not to mention economic upheaval with tens of millions out of work, America and much of the world face unprecedented conditions. If there is a drug out there that can actually work to shorten the virus infection duration or perhaps even reduce the death rate, why wouldn’t there be a “all hands on deck” to offer that drug to other researchers, should the sponsor pass. And that’s exactly what Public Citizen proposes here: why not “release permission so other researchers can pursue it.”
A Bridge to the Possible
Given the extraordinary circumstances, and assuming scientists such as Yan and Muller are correct, why wouldn’t Operation Warp Speed structure a deal with Gilead to make GS-441524 available to some generic developer, so that more people could access a compelling drug to at least help alleviate the pandemic’s impact? Well, unfortunately, it often comes down to money and profits. Public Citizen’s Dr. Michael Abrams emphasized, “It is sadly predictable that Big Pharma responds to a global pandemic by trying to bring to market only those drugs that maximize its profits” who was the lead author of the letter.
The reality is that Big Pharma (and for that matter little Pharma) must try to generate a return on investment; this necessity is built into the culture, otherwise investors don’t hold their stock, and these companies simply unravel. Given the enormous sums of money Operation Warp Speed is spending on various treatments, and the call for early state antivirals for example, why not pay Gilead to access this analogue of remdesivir, should it work?
The Portal to the Future of GS-441524
A framework for actually restructuring the horribly dysfunctional U.S. healthcare system, value based care was perhaps first introduced in a book back in 2006 authored by Michael Porter and Elizabeth Olmsted Tesiberg titled, “Redefining Health Care.” Characterized as a movement now, perhaps to some extent led by public (and some private) payers, increasingly the health care “fee for service” will morph into value-based payments. The trend, still in its infancy, starts to surface in drug pricing discussion for ultra-expensive gene therapy drugs, for example.
So what if Operation Warp Speed (OWS) could truly innovate, think out-of-the-box and structure a first-of-its-kind pandemic value-based payment model? Here is how it works. Gilead would offer to OWS an affordable license to develop GS-441524. OWS in turn would find the optimal drug development firm to take the license and develop the drug for use against COVID-19.
With tens of millions out of work and an unprecedented one quarter drop in GDP totaling 32.9 percent, American society (and many other societies) face what could become cataclysmic economic, social and political conditions should this pandemic situation not be alleviated soon. Hence, any contribution to such improvements—by beating back COVID-19—is incredibly valuable.
So assuming the product really does start working, cutting into viral infection duration times and perhaps even lowering of the death rates, the government could make multiple sizeable payments to Gilead based on the value this economical and effective drug contributed to societies. In this way, society benefits and Gilead benefits. But alas, so many are penny wise and pound foolish.
‘Money Often Counts too Much’
The theoretical payment model probably won’t get structured and in fact anyone of any importance at Gilead, or for that matter at OWS, probably doesn’t visit channels such as this one.
Back in the early to mid-19th century, while society was moving to a nascent stage for advancement, still pre-Civil War, certain “sheep-like” or herd behavior set in as overtly pious and perhaps outdated social beliefs were in many ways keeping American ingenuity, enlightenment—and importantly—economic thrust from progressing forward at the velocity and strength necessary for its unfolding historical precedent. That certain individuals decided to take contrarian positions than that of the “in crowd” of the times, ultimately helped transform that still young country to a powerhouse.
One such transformational character, Ralph Waldo Emmerson, an essayist, poet and transformational actor in his own way represented the emerging transcendentalist movement in the United States, driven by a powerful pursuit of individualism, connection to the inherent good of people and institutions, and revelatory challenger of the countervailing pressures of American society at the time. We leave the TrialSite network with an important quote of Mr. Emerson: “Money often counts too much.”