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 The U.S. pharmaceutical giant, which had begun exploring a vaccine,
also wanted to produce a pill that could stop the infection from
progressing, similar to how the widely-used Tamiflu drug fights
influenza. The team scoured Pfizer’s library of molecules looking
for unused compounds to help jumpstart the process, and quickly
identified a promising candidate.
More than a year later, Pfizer has yet to embark on large-scale
human trials of a COVID-19 oral treatment - something it says it
hopes to start by July.
Pfizer and its rivals, including U.S.-based Merck & Co Inc and Swiss
pharmaceutical Roche Holding AG, are racing to produce the first
antiviral pill that people could take at early signs of the illness.
Their shared goal: filling a key treatment hole by helping people
recently-infected with coronavirus to avoid becoming seriously ill
and needing hospitalization.
But after almost 18 months of the pandemic, there is still no
easy-to-administer treatment proven to be effective against
COVID-19, the disease caused by the coronavirus. That is despite the
development of a number of effective COVID-19 vaccines, including
one from Pfizer and German partner BioNTech SE, which in December
became the first to gain authorization for use in the United States.
Pfizer’s experience underscores the challenges drugmakers face in
developing an oral treatment for the virus. Unlike a vaccine, which
needs only to trigger the body's own immune system, an effective
antiviral pill must block a virus from spreading throughout the body
while also being selective enough to avoid interfering with healthy
cells.
Testing antivirals is also difficult, drug company executives say. A
drug needs to be given early in the course of an infection, which
means finding trial participants who have recently contracted
COVID-19. Many people infected with the virus develop only mild
symptoms, but studies need to prove that a drug has a meaningful
impact on patient health.
Pfizer Chief Executive Albert Bourla has said the company could seek
emergency authorization in the United States for a COVID-19 pill as
soon as late this year.
"Right now we have very good reason to believe that we can be
successful," Bourla told an economic forum in Greece via video
conference last week.
Pfizer and its rivals say the development process has been much
faster than the several years it typically takes to produce a drug
that can be taken as a pill.
Merck and Roche recently started late-stage human trials and have
also said their drugs could be ready by later this year. Merck is
developing its drug in partnership with biotech Ridgeback
Biotherapeutics LP and Roche is working with Atea Pharmaceuticals
Inc.
Governments around the world have poured billions of dollars into
vaccine development, but Pfizer, Merck and Roche say they have not
received government funding to develop oral antivirals for the
disease.
‘HUNT FOR THE NEXT TAMIFLU’
While the rate of new COVID-19 infections is currently in retreat in
some countries, others continue to struggle with a rapid spread of
the virus. And with vaccines in short supply in many countries, much
of the world will not be vaccinated for several years. Many people
also remain reluctant to take vaccines.
Scientists forecast that COVID-19 – which has killed more than 3.5
million people globally - could become a seasonal disease similar to
influenza.
"We need a pill that can keep people out of the hospital," said Dr.
Rajesh Gandhi, a professor and infectious disease specialist at
Harvard Medical School.
Doctors have tried a number of existing oral drugs in fighting
COVID-19, but none of them have succeeded yet in rigorous clinical
testing.
Currently, the only treatments shown to help COVID-19 patients avoid
hospitalization are antibody drugs that require lengthy intravenous
infusions and work less well against variants of the coronavirus.
Pfizer and its rivals say their oral antiviral candidates could be
effective against a broad spectrum of coronavirus variants, but no
relevant data has been made public.
For patients already hospitalized with COVID-19, treatment often
involves steroids or anti-inflammatory drugs to manage symptoms of
the infection, but these medications do not target the virus itself.
The only antiviral drug approved in the United States to treat
COVID-19 is Gilead Sciences Inc’s remdesivir, which is delivered
intravenously and used only for hospitalized patients.
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 Gilead is currently testing an
inhaled form of remdesivir and is exploring
other compounds that may be effective oral
agents.
"We are all on the hunt for the next Tamiflu,"
said Gilead Chief Medical Officer Merdad Parsey.
Tamiflu is recommended for people who have had flu for no more than
two days and has been shown to shorten the duration of flu symptoms.
‘CHEMISTRY MASTERPIECE’
Pfizer’s scientists and chemists began hunting for an antiviral
treatment in January last year. They quickly zeroed in on a compound
from 2003, when the company had sought a treatment for the first
global SARS pandemic, said Charlotte Allerton, Pfizer's head of
medicine design. The compound belongs to a class
known as protease inhibitors, designed to block a key enzyme, or
protease, essential to the ability of the coronavirus to multiply.
Similar drugs are used to treat other viral infections such as HIV
and hepatitis C, both on their own and in combination with other
antivirals.
Pfizer’s scientists hit an early stumbling block. Laboratory testing
showed the drug candidate was active against the novel coronavirus,
known as SARS-CoV-2, but concentrations were not strong enough to
combat the virus in humans, Allerton said.
Pfizer continued working with the active component of that compound
to formulate a drug that could be given intravenously. But
antivirals are most useful if you catch a disease early, “and that
isn’t easy with an IV drug,” said Allerton.
In March 2020, Pfizer scientists also started designing a new
compound that could be absorbed through the stomach and taken as a
pill, which they finalized in July, according to Allerton.
Discovering a protease inhibitor that could be delivered orally was
"a bit of a chemistry masterpiece," said Pfizer Chief Scientific
Officer Mikael Dolsten.
Antivirals are more complex to develop than vaccines because they
have to target the virus after it is already replicating inside
human cells, without damaging healthy cells. COVID-19 vaccines
typically teach the human immune system to recognize and attack a
portion of the “spike” protein that is specific to the coronavirus.
A COVID pill would likely be taken for only a few days, but
drugmakers have had to move slowly to ensure safety.
TRICKY TRIALS
The Merck and Roche drug candidates use different mechanisms to
Pfizer’s, and to each other, to disrupt the replication machinery of
the virus. But the companies share similar challenges in testing.
One is ensuring a patient receives the drug soon after infection
with COVID-19. “It's all about treating as early in the disease
process as possible, when the virus is expanding," Pfizer’s Dolsten
said.
And with vaccination rates high in some regions, trials have to be
located in countries where COVID-19 is still on the rise.
In March of this year, Pfizer began early-stage human trials in the
United States of its experimental oral COVID-19 treatment, known as
PF-07321332. It followed a separate trial by the company of the
intravenous drug started last fall.
Dolsten declined to comment on how the pending late-stage trials of
either drug will be structured.
Merck’s antiviral drug candidate, called molnupiravir, recently had
a setback. The company said last month it would not pursue its use
in hospitalized patients. But Merck said it was moving the drug into
late-stage trials of a narrow group of non-hospitalized patients -
specifically those who have had symptoms for no more than five days
and with at least one risk factor for serious disease, such as
advanced age, obesity or diabetes.
Merck said it could have definitive data by September or October.
Roche and its partner Atea are also limiting participation in their
recently launched late-stage trial of their AT-527 drug to COVID-19
patients experiencing symptoms for less than five days. Atea said
final trial results are expected before the end of this year.
(Reporting by Deena Beasley; Editing by Caroline Humer and Cassell
Bryan-Low)
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