No medicines are proven to treat the new coronavirus which emerged
from China late last year and has since jumped to scores of other
countries.
With little else but supportive care to check the virus’ rapid spread, doctors and scientists have launched
hundreds of trials in search of an effective therapy, testing mostly repurposed HIV or flu drugs.
Hopes are highest for remdesivir, an experimental antiviral developed
by Gilead for use against Ebola but since pressed into study for the
new coronavirus.
“There’s only one drug right now that we think may have real
efficacy. And that’s remdesivir.” said Bruce Aylward, a senior advisor
and international leader of the World Health Organization’s joint
mission to China, at a
Feb. 24 press conference.
Clinical trials are now underway in the U.S., China and, soon, other
Asian countries where high numbers of people are infected by the virus,
now named SARS-CoV-2. Preliminary results from the first of those
studies could come by April, Gilead expects.
Other drugs designed specifically to treat SARS-CoV-2 are now in
development but, for the next few months at least, much of the focus
will be on remdesivir. Here’s a primer on how it works, its potential
against the illness COVID-19, as well as why it’s no sure thing.
What kind of drug is remdesivir?
Remdesivir is designed to slow the infection of healthy cells by
blocking viral replication, checking the ability of an invading virus to
co-opt the body’s cellular machinery to reproduce itself.
In technical terms, it’s known as a nucleotide analog — meaning it
mimics a genetic building block, but with an unusual molecular group
tacked on. The thinking goes that, as the invading virus tries to
replicate itself, the drug gets in the way and stops the process.
Remdesivir emerged from work done by Gilead and U.S. government in
the mid-2010s to test compounds discovered by the biotech against
emerging viruses.
Initial animal experiments seemed to show the drug could work against Ebola, leading Gilead to start
Phase 1 testing in 2015 and
advance it into a mid-stage trial the next year.
A large Phase 3 study conducted in the Democratic Republic of the Congo, however, showed remdesivir to be
less effective in preventing deaths from the virus than two other drugs, leaving Gilead’s therapy with an uncertain future.
But the outbreak of SARS-CoV-2 made suddenly relevant a
series of experiments
in human cell cultures and mice that indicated remdesivir could have
activity against coronaviruses like MERS and, possibly, the new one now
spreading.
What evidence suggests remdesivir could treat COVID-19?
Gilead has taken pains to emphasize, when announcing new plans for
remdesivir, that it lacks human data on whether the drug actually works
to treat COVID-19.
What it does have is preclinical data showing the drug to be active
against the MERS and SARS viruses, which share enough genetic
similarities to SARS-COV-2 that researchers and the company think
remdesvir could work against it too.
Testing by National Institutes of Health researchers,
published in January,
demonstrated remdesivir prevented MERS from developing in monkeys, and
helped improve the condition of those animals that were already
infected.
“Our results, together with replication inhibition by remdesivir of a
wide range of coronaviruses in vitro and in vivo, may further indicate
utility of remdesivir against the novel coronavirus […] emerging from
Wuhan, China,” they wrote.
Most recently, an
in vitro study
conducted by scientists at the Wuhan Institute of Virology found
remdesivir and an anti-malarial called chloroquine more likely to be
effective against SARS-CoV-2 than a handful of other potential
treatments.
As remdesivir has drawn attention, many have focused on its
use in treating a Washington man
who tested positive for SARS-CoV-2 after returning from Wuhan. One week
into his hospitalization, doctors gave him remdesivir through a
compassionate use program that Gilead has been supporting.
The man’s condition began to improve the next day, sparking some
optimism about remdesivir’s benefit. But it’s not clear if the patient
had already begun to recover, as viral levels were declining before the
drug’s use.
How is remdesivir being tested now?
Early last month, doctors in Wuhan and Beijing opened two Phase 3
studies of remdesivir in coronavirus-infected patients with either
mild to moderate illness or with
severe disease. The former began enrolling on Feb. 6 and the latter a week later, on Feb. 13.
Together the trials aim to treat about 850 people and measure whether
intravenous remdesivir can improve or resolve the symptoms of COVID-19
over the course of roughly a month.
Investigators and Gilead expect results by April, which would give an
early signal of how likely the drug is to play a role in checking the
fast-spreading epidemic. Yet enrollment has not been as smooth as might
be expected. The WHO’s Aylward
noted last month
that a surge in studies of other potential treatments has made
recruiting more difficult, as have restrictions limiting who can join
the two trials.
In the U.S., a
study sponsored by the National Institutes of Allergy and Infectious Disease
recently began recruiting patients at hospitals in Nebraska and
Washington, with sites planned in Maryland and Texas. The first
participant was an American repatriated from Japan after being
quarantined on the Diamond Princess cruise ship in Yokohama harbor.
Other treatments could be added into the study in the future, which is designed to allow modifications over time.
Gilead, meanwhile, recently announced plans to start two of its own
Phase 3 studies in Asian countries where there are high numbers of
diagnosed cases. Those will enroll about 1,000 patients and begin
“within days,” Gilead CEO Daniel O’Day told reporters at a briefing in
Washington, D.C. on Thursday.
“By the time we get to the end of April, we should have a preliminary
idea of the safety and efficacy of this medicine against coronavirus,”
O’Day said.
How would remdesivir be used, if tests show a beneficial effect?
Despite the evidence suggesting remdesivir could work, it’s still an
open question whether that potential will translate into real efficacy.
There was preclinical and early clinical data suggesting the drug would
protect patients from Ebola, too, but results from that Phase 3 study
still disappointed.
“It is too early to place much confidence in the compound’s likely
activity against this virus, and even if it does prove active, we would
expect relatively modest activity in larger populations, rather than an
immediate and potent response such as could be seen with an
antibacterial,” wrote analysts at SVB Leerink in a recent note to
clients.
The drug’s dosing could also limit use, should tests show it to be
beneficial. The Phase 3 studies in China are using a 10-day course of
intravenously infused remdesivir, while Gilead is testing a 5-day course
in its trials.
Patients receiving the drug, therefore, would have to be in a
hospital and would likely need to be experiencing more serious symptoms
of COVID-19, such as pneumonia or shortness of breath.
And while remdesivir was used in hundreds of patients with Ebola, its
safety and appropriate dose have not been studied for COVID-19 as much
as typically would be the case with late-stage testing.
If remdesivir is proven, how would Gilead respond?
Gilead built up clinical supplies of remdesivir as part of its
testing the drug in Ebola, a stockpile that it is now using to provision
the studies in China.
But should those tests or trials in the U.S. and elsewhere prove
positive, Gilead will need to manufacture enormous quantities of the
drug to meet what would likely be extremely high demand from governments
and patients.
Gilead has said it is expanding its network of manufacturing partners
and has started internal production of remdesivir in preparation of
getting coronavirus data.
“We’re investing heavily in our supply chain and manufacturing such
that, should it work, we can respond immediately,” said Gilead’s O’Day.
“We’re investing tens of millions of dollars today, hundreds of
millions of dollars in the very near future to scale up manufacturing
facilities — both at Gilead and through a variety of partners — to make
this happen,” he added.
Another pressing question is remdesivir’s potential price, if proven and approved for emergency use.
Analysts at RBC Capital Markets expect Gilead would price the drug at
around $900 to $1,000 or lower per course, a cost above oral flu drugs
but below new intravenous antibiotics.
How Gilead approaches this question could be a potential flash point
between it and national governments, although the pressure of the moment
would likely factor into any decision Gilead might make.
For now, O’Day says the company hasn’t been discussing pricing in its
conversations with governments about clinical trials and compassionate
use.
“The topic of pricing comes up once you know whether the medicine works,” O’Day said.
“It’s very difficult to talk about pricing until you know what value
this medicine may or may not bring to patients and to societies,” he
said. “Having said that, we understand the public health need here and
we have to be very conscious about, should this work, how do we get this
in the hands of as many patients around the globe as fast as we can.”
https://www.biopharmadive.com/news/coronavirus-remdesivir-gilead-antiviral-drug-covid-19/573261/
