Reprinted with permission from trialsitenews.com

In the early stages of the COVID-19 pandemic, those involved in monitoring new drugs that may help inhibit the SARS-CoV-2 virus held out much hope for remdesivir, the antiviral drug developed by Gilead. But since the first studies, the results have been mixed, and the most recent World Health Organization (WHO) Solidarity trial produced yet another highly-significant piece of evidence concerning this controversial drug: In the largest trial involving remdesivir and COVID-19 to date, the drug doesn’t appear to help the sickest COVID-19 patients. Yet all along the way, U.S. federal agencies have been there, just at the right time, with a helping hand. Whether it was the unusual last-minute changes to the National Institute of Allergy and Infectious Diseases (NIAID)  sponsored ACTT endpoints, or the strong negative evidence generated from the Solidary trial, or for that matter, the mixed results that were already apparent from other studies in China, many in the scientific community grew increasingly leery of purportedly objective publicly-funded agencies such as the NIAID, part of the National Institutes of Health (NIH),  and the U.S. Food and Drug Administration (FDA).

Gilead Kept Quiet Until Deal Done  

Although FDA, the gold-standard regulatory body, has flexed its regulatory muscles when it comes to the COVID-19 investigational vaccine candidates, such as not bothering to use its Antimicrobial Drugs Advisory Committee (AMDAC) for an objective review before deciding to approve remdesivir (now called Veklury®). Meanwhile, although Gilead was aware that the Solidarity results were not looking good, its kept quiet until its nearly $1 billion deal was done with European Union deal makers. Some may consider this perfectly appropriate sharp dealing, while others may not be so generous, especially given the pandemic and its toll. Gilead critiqued the WHO’s trial design, in an attempt to pit the NIH/NIAID vs. the WHO, which is a mistake. By all appearances, Solidarity has an acceptable design, especially when considering its context: it was accomplished during the worst pandemic in a century. In the earlier days of the pandemic, TrialSite gave the benefit of the doubt to the company and federal players (regulators and research), but with the latest data points now available, the reality now unfortunately suggests that the approval was driven as much by economic and political considerations as by science and research.

Changing Endpoint, “Adaptive Study”

Most recently, Jon Cohen and Kai Kupferschmidt produced a piece for Science that offers a summary of the remdesivir story from the start of the pandemic to the present. The article raises uncomfortable and unfortunate issues, given the state of affairs with the COVID-19 pandemic. With over [10 million COVID-19 cases] and over [140,000 deaths], the US continues to represent the epicenter of the pandemic. Although India has four times the population of the US, nearly twice as many people have died in America due to COVID-19. The situation is horrific and not an appropriate time to support sharp dealing and profiteering. In TrialSite’s July 31 piece “Not a ‘Knockout Drug’ But Knocking it out of the Ballpark: Gilead Windfall as COVID-19 Sales to Hit $1 to 3 Billion in 2020,” we began expressing concerns about the relationship between federal agencies and Gilead. During the NIAID sponsored ACTT trial (NCT04280705), the sponsor (NIAID) changed the primary outcome measure (endpoint) at the conclusion of the trial  from how many people the drug kept alive on ventilators to how long it took patients to recover. Many suspect that NIAID did this to ensure the study would be successful. NIAID claimed that it simply followed the protocol—it’s an adaptive study, and in an unfolding pandemic, with so many unknowns that changes are normal. The study was blinded so those conducting the it would not have access to the data. Overall, the study found that introduction of the drug triggered a 31% reduction in duration of illness.

The New Standard of Care?

The San Jose Mercury News gave a helpful overview of some key points in an October 23 article, “Remdesivir, which will be marketed as Veklury, quickened recovery for patients hospitalized with COVID-19.” Gilead’s product was the first approved for serious cases, according to an announcement by FDA and Gilead on October 22. The announcement followed three Phase 3 trials which showed a reduction in recovery time. Critics have focused on the preceding news noted above from WHO: “Just days before the FDA authorization, the World Health Organization declared that the drug ‘has little to no effect’ on patients hospitalized with COVID-19, though its findings were not peer reviewed.” Gilead’s shares popped 4.5% following their own announcement. All of this some months after, in April, Dr. Fauci called remdesivir, “the new standard of care.” And CNBC chimed in on October 22 regarding the remdesivir announcement. They note that the drug obtained an EUA in May, allowing use for COVID-19 without formula approval. The article notes that earlier than month the “little of no effect” finding came in from WHO. Remdesivir costs $3,120 per five-day course for folks with private insurance. Gilead’s network for manufacturing remdesivir now includes over 40 companies across North America, Europe, and Asia.

 White House Announcement

The remdesivir announcement covered and broadcast for all, was delivered by Dr. Anthony Fauci in the Oval Office of the White House with POTUS. Fauci declared, “The data shows that remdesivir has a clear-cut, significant positive effect in diminishing the time to recovery.” The NIAID director went on to declare, as noted above, that remdesivir was the, “new standard of care” but also emphasized that it was “no knockout drug.” Gilead becomes the first company to deliver a blockbuster drug in such as fast period of time—in just four months the EUA was approved by FDA, opening the door to deal making. And of course, the rest is history as the drug was approved by the FDA on Oct 22 despite the fact that the overwhelmingly negative evidence produced in Solidarity was announced by WHO on October 15. Wouldn’t the FDA want to take the time to understand the Solidarity findings before pulling the trigger on permanent approval?

Regardless, by late spring and into the summer the controversy with Hydroxychloroquine unfolded, and ultimately the FDA revoked its EUA for that relatively cheap and available drug. Yet many physician-researchers still believe, if administered the correct way (e.g. early on), it can have some impact on slowing the progression of COVID-19. And let’s not forget the Ivermectin story; with the Monash lab findings, a wave of case series and observational studies through the summer produced significant data such that, if nothing else, the NIH should immediately start looking into this generic, already-approved anti-parasite drug. But to date there appears to be no interest. Why wouldn’t the NIH at least sponsor a study comparing Ivermectin to remdesivir?

Call to Action: Read Jon Cohen and Kai Kupferschmidt’s article titled “‘A very, very bad look’ for remdesivir.”

Lockwood Law

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