A common selective serotonin reuptake inhibitor and σ-1 receptor agonist, mounting data indicates that fluvoxamine prevents clinical deterioration in outpatients with acute COVID-19. This finding is based on the peer reviewed published results from a clinical trial involving 152 study participants who were confirmed with SARS-CoV-2-based symptoms within 7 days of study participation. Led by Dr. Eric Lenze and a team from Washington University School of Medicine in St. Louis, the study results indicate yet another important opportunity for a repurposed therapy targeting COVID-19. Although the investigators acknowledge that broader determination of clinical efficacy would require more research, the team was able to demonstrate in this study a statistically significant difference in the fluvoxamine group versus the placebo over 15 days. While the U.S. government continues to invest billions into vaccines and novel therapeutics for COVID-19, data such as this should be triggering considerable activity, including the inclusion of fluvoxamine in the ACTIV-2 study as an example. TrialSite’s Daniel O’Connor was also able to connect with prominent fluvoxamine supporter and sponsor Steve Kirsch for an informative dialogue about the potential of this therapeutic option currently half-way through a Phase 3 clinical trial called Stop Covid 2. Mr. Kirsch has committed his own money, time and brain power to an endeavor that should be supported by federal research institutions using American taxpayer-originated financing.
What is Fluvoxamine?
Traditionally marketed under the trade name of Luvox (and others), this antidepressant falls into the category of treatment known as selective serotonin reuptake inhibitor (SSRI). It is primarily used for the treatment of obsessive compulsive disorder (OCD) as well anxiety disorders, panic disorders and other conditions involving the central nervous system. The trade name was discontinued in the United States. Generic versions are produced by Abbott and Teva.
The drug has been around for decades now—it was first developed by a unit of Solvay Pharmaceuticals, a Belgium-based pharmaceutical company that was acquired by U.S.-based Abbott Laboratories in 2010. One of the very first SSRIs, it has been widely prescribed for decades now.
Interestingly, despite notable research centering on this CNS-focused drug in COVID-19 cases, the Wikipedia entry is silent on the topic.
According to UptoDate, “ limited data suggests that fluvoxamine may reduce progression to severe disease in early, mild COVID-19” but declares “high-quality evidence is lacking.”
Preclinical & Observational Views
A handful of preclinical and observational studies identified positive association of fluvoxamine and reduced impact of COVID-19. There are reports of observations at University of California, San Francisco, Stanford, and institutions in both Germany and France have reported possible significance.
For example, in France the largest hospital system in Europe called Assistance Publique-Hospitaux de Paris (AP-HP) collaborated with INSERM in what’s called the “HP COVID CDR Initiative.” In this multicenter observational retrospective study involving 545 adult patients with a mental disorder hospitalized with severe COVID, investigators found a positive association with the drug and positive impact. After multiple sensitivity and exploratory analyses, the result suggested some potential positive impacts of the drug in COVID-19 patients. Of course, the authors acknowledged the need for double-blind, controlled randomized studies of these medications for COVID-19.
In the meantime, it was reported in Germany that scientists at the Universities of Würzburg and Münster found that the acid sphingomyelinase (ASM) inhibitor known as fluoxetine possibly inhibits COVID-19 viral replication in cell cultures while German scientists noted that fluvoxamine “also an ASM inhibitor approved for depression, has a high affinity for the signal-1 receptor (S1R)” as well.
This means that elements within these molecules help regulate the production of cytokines during immune response. They found that in preclinical tests, the anti depression drug reduced cytokine production typical of severe sepsis, hence boosting survival. Of course, a cytokine storm in severe COVID-19 cases represents a potentially deadly direction.
In yet another real world-based observation covered on a CBS 60 Minutes episode, a real world treatment regimen led by Dr. David Seftel found a positive impact associated with fluvoxamine among the employees at a San Francisco Bay Area race track.
TrialSite took an initial look at emerging fluvoxamine human trials first at the University of Virginia School of Medicine, which was then followed by a significant study sponsored by Washington University School of Medicine in St. Louis.
The progress associated with this potentially repurposed drug hasn’t escaped notice; again, the mainstream press in the form of CBS’ 60 Minutes did an interview including Angela Reiersen, MD, a child psychiatrist with WUSM St. Louis and co-author of the study recently published in Journal of the American Medical Association (JAMA) as well as drug development philanthropist Steve Kirsch.
TrialSite hosted Dr. Eric Lenze, principal investigator of the Washington University School of Medicine fluvoxamine study, on the TrialSite Podcast series. TrialSite uncovered accumulating data that the drug exhibits considerable potential as one treatment option.
The promise of this therapy to reduce COVID-19 gained momentum with the support of philanthropist funding. Again, Steve Kirsch, an MIT-trained computer science and electrical engineer-turned successful technology entrepreneur helped raise the funds to support the fluvoxamine clinical development pipeline targeting COVID-19 via his COVID-19 Early Treatment Fund (CETF).
While Kirsch spends his own money to help society, TrialSite emphasized that the public National Institutes of Health (NIH)-backed ACTIV program (Accelerating COVID-19 Therapeutic Interventions and Vaccines)—spends to date over $15 billion targeting vaccines and novel therapies—this public-private partnership should also include repurposed therapies, such as fluvoxamine, in its research portfolio.
But that hasn’t happened, and its taken the active investment of Kirsch—his savings, time and brain power—to find treatments for early onset COVID-19 that not only work but that are economical, for the betterment of society. The NIH/ACTIV program appears heavily swayed by industry and rigid and seemingly detached academic thinking while the pragmatic, successful Kirsch seeks faster results that can potentially contribute to treating more people at a lower price point.
A One-Sided View of Ethics
TrialSite learned from Kirsch himself recently that “ethics” were under question despite the fact that he is giving his time, effort and money to identify economical treatments for the public. In a piece published by MedPageToday, University of Pennsylvania Perelman School of Medicine Steven Joffe, MD, MPH, and chief of medical ethics declared on some of Mr. Kirsch’s statements in blogs that the tech entrepreneur turned non-profit drug development sponsor “leapfrogs” evidence, essentially crossing an ethical line by declaring that the drug is effective.
TrialSite notes that throughout the United States, during the pandemic, various media have been touting investigational monoclonal antibodies, even before emergency use authorization. It has been quite common for local research centers via regional media affiliates to announce that the drug that former President Trump took (e.g. Regeneron or Lilly’s monoclonal antibody) was available to help care for COVID-19 patients in various studies (TrialSite can point to a number of examples for anyone interested). Such announcements cross ethical lines as they hint on advertising by healthcare-focused firms and organizations.
However, there was and hasn’t been any real ethical outcry by Mr. Joffe or others when the investigational drug is owned and funded by pharmaceutical companies. Those companies are gunning for major pecuniary gain.
Yet in the case of Mr. Kirsch, he continues to pour his own money into major research in a bid to establish definitive efficacy. Moreover, Kirsch has issued a $1 million award for anyone that can successfully demonstrate the existing evidence doesn’t present a compelling case. Thus far, no one has stepped forward to claim the award. Perhaps they cannot prove that Mr. Kirsch is incorrect?
Typically ethical challenges are truly relevant when the parties have financial-based conflicts of interest—which is often. Merck, for example, completely denounced their own product ivermectin and the mounting evidence of positive clinical efficacy, declaring there is no evidence for research efficacy targeting COVID-19. Of course, based on over 50 positive clinical trials, this claim was patently false and disrespects investigators’ efforts around the world.
Of course, Merck had a financial interest to not only completely refute dozens of study results but also actually claim safety threat possibility with their own drug—one they gave away to hundreds of millions in the tropics. Just prior to Merck’s claims, they spent $425 million to acquire a biotech working on a therapeutics venture. The following month, the New Jersey-based pharma accepted $356 million of taxpayer money to develop this same drug. This raises eyebrows yet no academic ethics chiefs say anything about ethics.
In an interview with Steve Kirsch, he did share with TrialSite that this ethics officer was open to changing his position with Kirsch should the data conclusively prove him (Kirsch) correct.
Discussion with Steve Kirsch
TrialSite’s founder Daniel O’Connor was able to catch up with Steve Kirsch. Thanking him for personally financing an important potential repurposed therapy, Kirsch reported first on the growing censorship in the usual social media channels, from Medium to YouTube and Facebook. That’s right: the top social media sites are punishing a man that’s committed huge amounts of his own personal savings to progress therapies for the public—truly a disturbing development, but unfortunately not a surprising one as TrialSite becomes the target for censorship by social media for simply declaring facts.
An unwavering advocate for public health, Kirsch’s commitment and drive for the people’s benefit is easily apparent in pursuing his goal for helping people avoid Long COVID and death. He posits that there is just enough data, based on risk-reward analysis, to use the drug off-label with informed physicians and of course consenting patients.
Because of his role in financing fluvoxamine research, Mr. Kirsch has discussions across the country and beyond, from Europe to India. He accounts that physicians he knows have treated hundreds of patients with no hospitalizations. He told TrialSite’s O’Connor that Dr. George Fareed has treated thousands of patients with both fluvoxamine and ivermectin, and the only hospitalizations occur when patients are treated too late in the diseases’ lifecycle (e.g. days after onset of symptoms).
Based on the accumulation of observational and clinical data, Kirsch suggests serious consideration of off label use given the severity of the situation—with 570,000+ deaths in America alone.
O’Connor and Kirsch both agreed that an online conference focusing on repurposed therapeutic approaches to COVID-19 cases—including trial status updates and public debates with representatives from the National Institutes of Health (NIH) and the Food and Drug Administration (FDA)—would be a positive and healthy contribution to the public knowledge at this point in the pandemic.
Mr. Kirsch told TrialSite that the treatment has been used for nearly four decades and is very safe if used at current regulatory indicated dosage. He noted that a lower dose is used to treat COVID-19 in off-label scenarios, and that based on the data thus far, the probabilities are too high to ignore—he implores to physicians around the nation to at least learn more about what’s going on with fluvoxamine as well as ivermectin.
Recently Published Trial Site Results
Based on the Phase 2 Stop Covid study (NCT04342663), WUSM St. Louis investigators reported recently in JAMA that those patients with early onset COVID-19 symptoms have a lower likelihood of clinical deterioration over 15 days. While the study size was limited—with a brief study follow up period, nonetheless the results certainly indicated statistically significant results.
Phase 3 Stop COVID 2 Study
TrialSite reported recently that the University of Utah now participates in a COVID-19 focused fluvoxamine study. In fact, the Stop COVID 2 Phase 3 pivotal clinical trial, (NCT04668950) led by WUSM St. Louis targets 1,100 participants to use the treatment for early course COVID-19 infection and prevent more serious complications, such as shortness of breath. This fully-remote study has been designed to help individuals take advantage of the learnings thus far—that statistically, in smaller studies, Fluvoxamine shows some benefit. This is a big deal, and if this study can generate efficacious results over the next months, the implications are significant. This study’s collaborators include McGill University and Kirsch’s COVID-19 Early Treatment Fund.
Call to Action: TrialSite posits the importance of federal dollars backing the fluvoxamine research based on the promising data and the growing demand for low cost treatments for early onset COVID-19 cases, representing 90% of the total cases. Interested in supporting this effort? Donate to the COVID-19 Early Treatment Fund. Also check out TrialSite Opinion Editorial as Mr. Kirsch will soon be a featured author.