Reasons for FDA rejecting fluvoxamine as a Covid-19 drug

Covid-19 drug

Researchers who were looking at cheap generic medications hoping to find one that could work
as a Covid-19 treatment came upon a promising option that was the antidepressant
fluvoxamine.


In a large controlled, randomized trial known as Together researchers from McMaster University
compared eight different recycled drugs and concluded that the most of them, including
ivermectin which is the antiparasitic hailed by many as a Covid-19 cure miracle did not do much
to fight the disease. However, fluvoxamine was found to reduce severe cases by 30.
Fluvoxamine has shown some potential in small-scale trials in small-scale studies last year,
However, smaller-scale trials can sometimes yield poor outcomes, which is why the vast
majority of people didn’t consider fluvoxamine to be a serious option until they saw the
impressive results from the Together trial.


“This already feels different from hydroxychloroquine and company were given the high quality
of the research,” Paul Sax stated within NEJM Journal Watch, which reviews recent research.
“We might finally be onto something.” Federal regulators, however, were more skeptical, due to
the fact that the regulatory system wasn’t intended to allow for the addition of new indications to
medicines that are already accepted through the FDA without any pharmaceutical company
sponsoring them.

Another researcher who was convinced of the need for fluvoxamine, David Boulware decided to
take the matter on his own. The FDA was unsure of how to handle the submission of a drug that
needed which be approved to use for a brand new indication. Without a responsible person for
the proposal? Fine. He’d make it his own. In December of the same month, he submitted an
application for emergency use of fluvoxamine to treat Covid-19.
In many ways, it was a heartwarming story about the potential of citizen science. But it wasn’t
how it ended up.


This week, the FDA declined the application for an emergency use authorization for
fluvoxamine. The FDA’s regulators argued that the results of the Together trial were more
uncertain than they had hoped. The majority of benefits were related to a decrease in prolonged
observation in the emergency department the endpoint was quite specific to the clinical
environment of the study in Brazil and isn’t necessarily of them. They also pointed out that,
following the Together trial, other studies have been conducted to discover any evidence for the
benefits of fluvoxamine however, they haven’t generally found results that are as big.


In a rare move In an unusual move, the FDA issued an explanation of the reason for the
rejection and in the majority of cases, it’s quite sensible. However, the entire episode highlights
the flaws in the way we evaluate and approve the use of drugs.

The Game Of Drugs

For the past eight months in the meantime, for eight months, the National Institutes of Health,
which keeps a database up-to-date of research findings on treatment options for Covid-19, did
not update the fluvoxamine webpage with any information about the latest, promising research.


(The NIH states on the page the same way it did for the past year the following “There is
insufficient evidence for the COVID-19 Treatment Guidelines Panel (the Panel) to recommend
either for or against the use of fluvoxamine for the treatment of COVID-19.”)
This has frustrated researchers, particularly during the winter months when the number of cases
of omicrons began to increase and the best treatment options for Covid-19, such as Paxlovid
which is a popular treatment, were not widely accessible. Many of them informed me that with
these results that the FDA would not approve a medication that has a pharmaceutical firm
backing it. They also said that the reason fluvoxamine was not working was the most significant
benefit: it was inexpensive and popular.


To be precise, fluvoxamine has been prior to being approved by FDA for the treatment of the
obsessive-compulsive disorder (OCD). Doctors can therefore use it within any situation they
believe is appropriate and is often prescribed off-label for anxiety as well as depression. It’s also
possible to prescribe off-label to treat Covid-19, however, most doctors don’t want to make
off-label prescriptions. That’s why those who advocated for the drug asked the FDA to confirm
that fluvoxamine is also recommended for Covid-19 in the order for it could be treated for this
condition could be added to the list of applications alongside OCD. However, many experts
were skeptical

“I don’t think the FDA ever will approve it for Covid,” Eric Lenze who was co-author of
preliminary research about fluvoxamine, told me back in December. “The reason why the FDA
isn’t going to allow it to be used for Covid is precisely why it’s so effective for Covid that is, it’s
inexpensive and widely accessible. There is no way to earn profits from it, therefore there’s no
reason to pay the cost to ask the FDA to let it go through.”


“The guidelines are overly conservative in that they have not yet endorsed fluvoxamine,” Ed
Mills, one of the researchers who led the Together trial said to me in November. What is the
reason for the FDA not giving fluvoxamine the same kind of review it gives other drugs? “They
don’t know how to deal with submissions where there isn’t someone to be responsible for it,”
Mills stated. The procedure of adding an indication is typically initiated by the company that
developed the drug and their lobbyists who work together with FDA to ensure that they’re
submitting the information that the FDA is looking for approval.


The research on Fluvoxamine was largely funded by the Fast Grants which is a private
philanthropic initiative to help ensure that Covid-19 research happens and, since it is a generic
drug, nobody could profit through its approval for Covid-19. “It’s very disappointing as a scientist
to see that it’s actually not about clinical evidence, it’s about lobbying,” Mills explained to me.

The FDA’s rejection notice last week clarified their reasoning and clearly, it’s not solely about
lobbying.

It is important to recognize that the main reason to use fluvoxamine as a treatment has become
less convincing than it was when Boulware made the application. In the past, there was a major
lack of effective treatments for Covid-19 that could be administered at home instead of in a
hospital. Monoclonal antibodies, which were the initial method of treatment used in earlier
phases of the pandemic, were not effective against Omicron. Other treatments were advised for
patients who were hospitalized. There was not a single medication one was able to take on their
own if their condition was not severe enough to stop the development of serious illness.


Presently, there’s an antiviral medicine called Paxlovid. Fluvoxamine’s biggest advocates are of
the opinion that Paxlovid performs better and appears to decrease the severity of disease by
between 80 and 90 percent. While the winter of 2009 Paxlovid was in short supply but today,
there’s a plethora of doses available in the US — even though many affected Americans remain
unable to get the medication due to a shortage of primary care physicians who they can speak
to as well as a large number of physicians are unsure of the best time to prescribe the
medication.


However, Paxlovid isn’t a cure-all but it’s advantageous to have more options available in our
inventory. “There are many effective treatments available. However, not all people have access
to these therapies. They are not for everyone. Certain people are contraindicated,” Boulware
argued in response to the FDA decision to reject. “And if you go elsewhere in the world, low-
and middle-income countries, they have access to no therapeutics.” However, the fact that
Paxlovid which is a much better alternative is currently widely available, weakens the argument of fluvoxamine being available in the US even though other countries with no Paxlovid access must decide on their own.

The Covid-19 treatment we have failed to treat

The majority of the time, if you were positive for Covid-19 the recommendation from health
officials was to take nothing until the symptoms deteriorated. In the past, the official CDC
webpage on what to do if you are suffering from Covid-19 was to wear masks and wash your
hands and wipe clean surfaces so that you don’t spread the disease to people near you. If your
breathing becomes more difficult or you are showing symptoms of a severe illness such as
confusion or inability to remain awake and alert, the CDC recommends going for a hospital visit.


Recently the CDC has added a box that states that if you’re at the highest risk of developing a
severe illness, treatment may be accessible. However, for those who aren’t considered
high-risk, which includes elderly people or those suffering from medical ailments The
recommendations aren’t a complete list of treatment alternatives.


In the beginning, the absence of treatment suggestions was probably because the evidence
supporting any treatment was poor. In the early days of the pandemic, treatments such as
hydroxychloroquine were a big hit but didn’t perform. In the following years, ivermectin was
touted as a miraculous cure. (It isn’t.)
However, the absence of treatment options was the result of a system that was not very
effective in making them clear and distributing that information to the public in a confusing
manner. The fluvoxamine clinical trial as well as numerous other clinical trials of future
treatments — were funded through private philanthropy, as the processes of government were
inefficient to be relying on. NIH official recommendations pages intended to provide a summary
of the state of research in different treatments that were frequently years out of date. I posted in
December 2021 that the page for fluvoxamine was last updated in April, the year before.


And instead of FDA cooperating with researchers to create clinical trials, which the agency
could use to suggest or decline medications, researchers had created and conducted the
studies themselves. And then certain doctors were required to submit a EUA application to
request the FDA to examine the work they’d conducted.
The requirement for fluvoxamine is not as strong The evidence is not conclusive and the FDA’s
choice not to endorse the drug is quite sensible. However, in ideal circumstances, it would be
ideal that the FDA would have been involved in the process of research from the moment
fluvoxamine first began to show potential and the government could have been involved in the

design and financing of more thorough trials, instead of waiting for a proposal from a group of
citizens. The fact that evidence on fluvoxamine is not conclusive at the moment is a reason enough not
to grant a EUA however it’s also an indication of an obvious flaw in our process of evaluating
promising treatments for Covid-19. Covid-19 will remain with us for quite a while, and there are
other pandemics in the near future.

The method of developing treatment options — and also
communicating with the public about them is in need of improvement.