44 | New Scientist | 13 February 2021
There have been thousands of
randomised controlled trials of
prospective drugs for covid-19,
but so far regulatory agencies
have approved only three:
the antivirals remdesivir and
favipiravir, and the widely
used anti-inflammatory
dexamethasone (see main story).
Making sure new compounds
are safe and effective medicines
takes a long time, and the broad
strategy has been to focus on
three main kinds. This is the
progress so far.IMMUNE MODULATORS should
work by reining in the body’s
potentially dangerous overactive
immune response to covid-19, as
is the case with dexamethasone.
Tocilizumab and sarilumab,
already approved for use in
autoimmune conditions in the UK
and US, have been investigated as
treatments for covid-induced
pneumonia in 13 countries in
people over the age of 50 as part
of the REMAP-CAP trial. In January,
it was announced that the two
drugs together reduced the need
for ventilators and intensive care
treatment by a quarter.The University of Oxford’s
AVID-CC trial began in September
2020 to test adalimumab, which is
used to treat inflammatory bowel
disease and arthritis. The study was
prompted by observations that
people with covid-19 in care
homes who were already taking
adalimumab were less likely to
need hospital care. That trial is still
under way.ANTIBODIES are the body’s
defenders. When we are infected
with a pathogen, our immune
system produces these proteins,
which bind to the invader. This
alerts the rest of the immune
system to a pathogen’s presence
and prevents it from multiplying.
It had been hoped that injecting
antibodies from people who have
recovered from covid-19 might
protect those who are newly
infected, but trials of this
convalescent blood plasma
have had mixed results. The UK’s
RECOVERY Trial stopped recruiting
people to test convalescent plasma
after preliminary data showed it
wasn’t beneficial.
Single antibodies have also
been synthesised in the lab. Thesemonoclonal antibodies act like the
proteins produced by the immune
system and are being investigated
both for their ability to treat
infected people and to prevent
infection (see “Covid-19
prophylactics”, below).
The US Food and Drug
Administration has granted
emergency use authorisations
for monoclonal antibodies from
pharmaceutical firms Eli Lily and
Regeneron – and two studies
show that these drugs can cut
hospitalisations and deaths. As yet,
however, both the US National
Institutes of Health (NIH) and the
Infectious Diseases Society of
America say there isn’t enough
evidence for their routine use.
A trial investigating two
monoclonal antibodies synthesised
by biotech firm Brii Biosciences
kicked off in January to see if they
can prevent hospitalisation and
death at 28 days of infection. More
than a dozen other studies of
monoclonal antibodies are under
way globally.ANTIVIRALS work by stopping a
virus from replicating. Many early
hopes for a quick end to thepandemic were pinned on
remdesivir, developed by Gilead
Sciences to combat Ebola. Tests
had shown it was safe but not
effective against Ebola, but maybe
would work against covid-19.
In May 2020, early results of a
trial, including more than 1000
people hospitalised with covid-19,
showed that remdesivir decreased
recovery time from 15 to 10 days.
In the US, UK and EU, the drug has
been approved for hospital patients
with severe disease and its use has
become fairly routine. However,
other trials, such as the World
Health Organization’s Solidarity
Therapeutics Trial, including
11,000 adults in 30 countries,
showed no benefit to survival. The
WHO doesn’t recommend the drug
for any patient.
“We’re trying to resolve some
of these differences in data on the
NIH COVID-19 guidelines panel,”
says Clifford Lane at the US
National Institute of Allergy
and Infectious Diseases.
Antiviral drugs developed for
other diseases are also being
investigated. Influenza drug
favipiravir has been approved to
treat covid-19 in China, Italy, India
and Russia. HIV drug lopinavir-
ritonavir unfortunately hasn’t
proven successful in clinical trials.
Still, broad-spectrum antivirals
remain a goal. In August 2020, the
Corona Accelerated R&D in Europe
(CARE) consortium launched to
develop monoclonal antibodies
and broad-spectrum antivirals
over the next five years. Even if it
doesn’t find anything to help this
time, it will help us prepare for the
next emerging infectious disease,
says CARE co-leader Kumar
Saikatendu at biopharmaceutical
firm Takeda, a CARE participant.
“The expectation ultimately will
be to create not only an effective
medicine, but an affordable
medicine that can be globally
distributed, even to remote places
of Africa and Asia,” he says.Covid-19 prophylactics
Where are the medicines?
Vaccines are the best
option to prevent covid-19
infections, but they still aren’t
widely available throughout
most of the world. Even once
they have been widely rolled
out, there will be people who
can’t be vaccinated. So we
need other ways to protect
people from infection.
Early findings on
monoclonal antibodies called
casirivimab and imdevimab
from pharmaceutical firm
Regeneron have shown that
they may prevent disease inpeople living in the same
house as someone with
covid-19. Eli Lilly’s
monoclonal antibody called
bamlanivimab showed
similar benefits to nursing
home residents.
A review of other
potential prophylactic drugs
currently in trials was less
encouraging. It primarily
included existing medicines,
rather than new compounds
being developed specifically
for covid-19, but joined
the chorus of researchconcluding that the
anti-malarial drug
hydroxychloroquine makes
no difference to recovery
from covid-19, and that
there isn’t enough evidence
for other drugs.
Areas in Africa where
the anti-parasitic drug
ivermectin is widely used
have noticeably lower rates
of covid-19 infections, which
has inspired hopes that
it could be an effective
prophylactic. This is now
under investigation.