Friday27 March 2020 ★ FINANCIAL TIMES 15

FT BIG READ. MEDICAL SCIENCE

A vaccine is at least 18 months away, believe scientists. But pharmaceutical groups are now adapting

existing treatments to help slow the outbreak, amid intense political scrutiny of their work.

By Hannah Kuchler, Kana Inagaki and Sarah Neville

ible resources and financial costs when

you’ll never get repaid if the virus is suc-

cessfully contained?”

Even if a drug succeeds, there will be

political pressure to price it affordably.

Rising Pharmaceuticals, a generic

maker of chloroquine, almost doubled

the price to $7.66 per 250mg pill in the

US in January, as the coronavirus out-

break raged in China. This month, as the

crisis hit the US, it cut the priceto its

previous level.

AbbVie, maker of the HIV drug com-

bination, will allow generics makers to

manufacture the drug, relinquishing its

intellectual property claims, in a move

that should make it cheaper.

Drugmakers will need to make large

investments to increase production fast.

Kenneth Kaixin, director of the Tufts

Center for the study of drug develop-

ment, says: “You don’t want to invest a

lot in manufacturing before you know

you are going to have a drug on the mar-

ket. [Yet] you want to make sure you

can manufacture as much as needed,

perhaps hundreds of thousands of

doses.”

Once a drug is ready to sell, govern-

ments are likely to compete to put their

citizens first. Already, there are reports

that the White House tried tobuy Ger-

man vaccine maker CureVac, with Ber-

lin trying to find ways to keep it at home.

The UK has banned the “parallel

export” of threedrugs: Kaletra, chloro-

quine and hydroxychloroquine, so

wholesalers cannot buy drugs intended

for UK patients and sell them elsewhere.

Some believe the pharmaceutical

business model simply does not work

for pandemics, becausediseases will

always compete for resources with

blockbuster drugs that people take for

years.

Emergent Biosolutions takes a differ-

ent approach: it specialises in making

“rescue therapies” for unlikely events,

selling the only antidotes to smallpox,

anthrax and botulism to US and allied

governments to stockpile in case of bio-

terrorism. It is now working on an anti-

body treatment for Covid-19.

“What differentiates us from just

about any other pharma company is

that they want an immediate return,

within six to 12 months, and we take a

little bit of a longer view,” says Robert

Kramer, chief executive of thespeciality

pharmaceuticals company.

Despite the obstacles, finding drugs

that can be repurposed to help corona-

virus patients’ recovery is one of the

only hopes for their health, their fami-

lies — and ultimately, the economy.

Dennis DeBusschere, who leads Ever-

core’s portfolio strategy team, is closely

watching when medications might be

ready, because he believes they are key

to getting those people currently in lock-

down back outside to spend again. Even

if the virus continues to spread, having

medications available would take some

of the fear out of infection.

“You may want to go on vacation

again, actually go to a restaurant, to the

movies,” he says.

Additional reporting by Wang Xueqiao

From the briefing room at the White

House, President Donald Trump last

week told the watching nation that the

“beauty” of drugs like chloroquine is

they can be taken safely. But while the

drug has been approved to treat

malaria, it can cause acute poisoning.

Within days, patients in Nigeria,

Vietnam and the US were hospitalised

for overdosing on chloroquine. One

couple in Arizona imbibed the unsafe

fish food version of the compound—

and the man died.

Mr Trump, inset, has persisted,

tweeting charts from studies that

experts believe are inadequate to base

such a decision on. But a pandemic is not

fought on anecdotes. Anthony Fauci,

head of the National Institute of Allergy

and Infectious Diseases and a member

of the coronavirus task force, said

the studies were not controlled

clinical trials. “Anecdotal reports

may be true, but they are

anecdotal,” he said on March 21.

Senator Patty Murray, the

ranking Democrat on the health,

education, labour and pensions

committee, says: “It’s irresponsible for

President Trump to get ahead of the

experts on something like this with

reckless guesswork. We have to make

sure we are following the science and

getting people reliable information, not

shooting from the hip and creating new

Treatments

Trump criticised over

‘reckless guesswork’

I

t is just 14 dayssince doctors at

Northwell Health, the largest

healthcare provider in New York

City, decided to take the search for a

coronavirus rug into theird own

hands. Many of their Covid-19 patients

were not getting better — and some were

getting worse.

Two of the hospitals’ scientistscalled

their contacts at US biotech companies

Gilead nda Regeneron o offer to testt

their potential treatments: an antiviral

called remdesivir and an anti-inflam-

matory called Kevzara, developed for

Ebola and rheumatoid arthritis respec-

tively. Clinicians, researchers and regu-

lators scrambled to set up the clinical

trials, which usually take months, and

four days later, two patients took their

first doses of the experimental drugs.

“The patients were very, very sick,”

says Kevin Tracey, president of the Fein-

stein Institutes, the research arm of

Northwell Health. “After30 years of

doing research, it was one of the proud-

est days of my life to know patients were

getting treated with these drugs that

may help them.” The hospital hopes the

drugs will stop the replication of the

virus and reduce inflammation in the

lungs.

As the global pandemic spreads —

recorded cases have more than doubled

over the past week to almost 500,000,

with more than 22,000 deaths— no one

can afford to wait the 18 months it might

taketo find a vaccine. Northwell is one

of many hospitals across the globe run-

ning clinical trials on drugs that were

developed for other diseases, from

Ebola to malaria to arthritis, but which

early studies suggest could offer some

hope to Covid-19 patients.

Doctors are desperate for evidenceof

what works. In the next month, they will

learn more as some key trials in China

are due to publishpreliminary results.

Yet the desire from politiciansand

investors or a miracle cure has led to af

maelstrom of misinformation about

drugs for the virus. Just as Northwell

was dosing its first patients, President

Donald Trump said the Food and Drug

Administration had approved the anti-

malarials chloroquine and hydroxy-

chloroquine for use against Covid-19.

This turned out tobe wrong, withfatal

consequences. The FDA isjustcollect-

ing evidence n whether they work.o

Christos Kyratsous, vice-president of

research in infectious diseases at Regen-

eron,says anecdotal evidence from

China is a reason to be “optimistic” that

Kevzara, developed withSanofi, will

help Covid-19 patients suffering from

acute respiratory distress syndrome.

“The challenge now is finding the best

and quickest way to see if it is effective

in the clinic,” he adds. “That’s very, very

important, because if you can get mean-

ingful data, and if the data is positive, we

can expand access to something like

this, which is going to be life saving.”

Drug options

Scientists are investigating three main

types of drugs. The first are antivirals to

stop the virus from replicating. Treat-

ment guidelines compiled by the Chi-

nese government during the outbreak

include HIV drug combinationKaletra,

which US biotech AbbVie recently

waived its patents on so it can be made

available as a generic; antimalarials

such as chloroquine, which generic

drugmakers are gearing up to manufac-

ture at scale; and favipiravir, an anti-flu

drug from Japan’s Fujifilm.

The second category is anti-inflam-

matories that treat the lungs after the

immune system is overwhelmed.

Regeneron and Sanofi have partnered

on Kevzara, while Roche hasstarted a

trial on Actemra, approved for use on

rheumatoid arthritis in 100 countries.

The third group are antibody-based

treatments, derived either from recov-

ered Covid-19 patients or developed in

labs, to be given to the seriously ill or as a

temporary prophylactic for healthcare

workers.Eli Lilly as paired up withh

Canadian start-up AbCellera to work on

antibodies developed from one of the

first US Covid-19 patients, while Japan’s

Takeda s developing a new drugi

derived from the blood plasma of others

who have survived the virus.

Analysts are eagerly awaitingdata

from early trials into Gilead’s remdesi-

vir, an antiviral drug that the California-

based biotech developed for Ebola, but

has also been shown to work against

other coronaviruses in animal studies.

Umer Raffat, a biotech analyst at US

bank advisory firm Evercore, ays evi-s

dence could be published in the next

couple of weeks.

designed to prevent bias. A study in

China released on Tuesday found the

drug had no impact.

Early results from clinical trials in

China fuelled enthusiasm for a second

antiviral — favipiravir — after reports of

faster recovery times for patients that

took the drug. Junji Okada, president of

Fujifilm Toyama Chemical, the unit that

produces the branded version Avigan,

says the company isresponding to a

flood of inquiries from across the world.

“Our sense of mission became bigger

and bigger as it became clear that Avi-

gan may be effective,” Mr Okada says.

“We have made the preparations so that

we can increase production if needed.”

Refining the product

Antibody-based treatmentscould be

important for helping the hardest hit

and those key workers thatneed to stay

healthy. With New York City now the

centre of the crisis in the US, with almost

300 deaths, the wider state is set to start

testing plasma from recovered patients

in a trial with the seriously ill. But most

drugmakers are looking at refining the

process to create a concentrated and

purified product, or creating artificial

antibodies, often developed in mice.

Their products will have to go through

clinical trials, likely to take many

months.

AbCellera^ was working on a test

project on influenza and another coro-

navirus with the US Defense Advanced

Research Projects Agency whenCov-

id-19 emerged. It rapidly switched to

preparing itsantibody-finding platform

for the new virus. After taking blood

samples t wasi able to generate almost

6m immune cells from just one patient

for antibodies, using an AI-based plat-

form that can screen down to the indi-

vidual cell and allows them to find more

antibody-secreting cells. Researchers

have narrowed it down to the 500 most

potent against Covid-19 and partnered

with Eli Lilly for the first human trials of

the drug by July.

“Every day between now and the first

human testing is mapped out and pre-

cious,” says Daniel Skovronsky, chief

medical officer of Eli Lilly.

Takeda beganlooking at plasma-

derived therapies after they proved

effective in reducing mortality during

the outbreaks of both severe acute res-

piratory syndrome (Sars) in 2002-

and Middle East respiratory syndrome

(Mers) in 2009. But the treatment will

not be widely available — the plasma

will need to be donated by recovered

patients. It is not yet known how many

peoplecould be treated with the plasma

from a single recovered patient.

Another obstacle is that all the drugs

being tested have potentially serious

side-effects: remdesivir may cause liver

damage, Avigan can cause birth defects,

and Regeneron and Sanofi’s Kevzara

work by suppressing the immune sys-

tem — but it could potentially go too far.

Rajeev Venkayya, president of

Takeda’s vaccine business, says the

industry is facing a new challenge. “It is

unprecedented,” he says. “[But] what is

very different is the opportunity we

have with the tools and technologies

that can help us to address this in ways

that we didn’t have in the past.”

Investment focus

Drugmakers face similar challenges to

vaccine developers: by the time they

have the evidence they need, the new

virus may have disappeared. But at least

it is now clear that Covid-19 is likely to

be a longer-term problem.

“When it becomes a global health cri-

sis, it is easy for companies like us to

make decisions to invest... There is a

concern for wellbeing, patients, soci-

ety,” says Dr Skovronsky. “But when it

first emerges and there are five or 10

patients, is it worth spinning out incred-

problems for patients.”

Bruce Lewenstein, professor of

science communication at Cornell,

says hailing a drug as a sure bet too

soon had already led to a run on

chloroquine, depriving people

who need it, such as patients

with lupus, and could make it

harder to persuade people to

participate in trials for what

could turn out to be better

therapies.

“You need to have spokespeople

who are being honest and trustworthy

about what they know and about what

they don’t know,” he says. “President

Trump, clearly, deeply believes in his

own expertise and his own ability to

make judgments about many, many

different complicated things.”

“It has by far the best prospects,” Mr

Raffat says. His optimismstems from

the drug’s ability todisable the machin-

ery that helps the virus replicate, which

is similar to thatfound in Ebola, but the

early datamay not be “spectacular”, if

too many of the patientstook it too late

in the progression of their disease.

Andre Kalil, an investigator in a large,

remdesivir trial, which plans to recruit

400 patients and is sponsored by the US

National Institutes of Health, says they

are making patients take the drug

within 72 hours of diagnosis. Dr Kalil

ran a clinical trial during the 2014Ebola

outbreak. He believes they moved too

slowly to set up a trial then.

“This is a fight against time. We need

to move as fast as possible,” he says. “We

have no idea what works or does not at

this point. There are zero therapies spe-

cifically againstcoronavirus.”

Timing was also important n an earlyi

study published last week of the HIV

drug combination which was dismissed

as disappointing, though survival rates

were better whenpatients had taken the

antiviral drug earlier in the disease.

The antimalarial chloroquine does

have two clear advantages over remde-

sivir: it is a generic, so is likely to be far

cheaper; and it is a pill, when remdesivir

is delivered by an intravenous infusion,

so would probably need to be given in

hospital. Butstudies in France and

China, hailed by Mr Trump, are small

and did not follow the recommended

protocols of a randomised control trial,

‘This is a fight against

time. We need to move as

fast as possible. We have

no idea what works or

does not at this point’

The hunt for a

drug to treat

coronavirus

Northwell

Health Labs,

above, is testing

remdesivir,

developed to

treat Ebola, and

Kevzara, which

tackles

rheumatoid

arthritis, for use

againstCovid-19.

Below: anEbola

patient being

treated in the

Democratic

Republic of

Congo— FT montage

Antivirals

Drugs designed

for treatment of

Ebola, HIV, flu and

malaria. They try

to stop the

replication of

coronavirus by

interfering with

enzymes that help

it copy itself. They

are believed to be

most useful in the

earlier stages of

the disease. The

virususes the

same machinery to

copy itself as

Ebola, giving

some experts

hope that Gilead’s

Ebola drug

remdesivir may

help patients.

Drug groups to tackle Covid-

Anti-

inflammatories

Designed for

conditions such as

arthritis. Several

groups rea

investigating the

potential of IL

inhibitors, which

lowerthe

production of

inflammatory

proteins called

cytokines. They

are most useful in

the latter stages of

the disease, when

some patients

suffer from acute

respiratory

distress syndrome

whenimmune

systems become

overwhelmed.

Antibodies

Drugs derived

from Covid-

patients’ immune

response. They

reproduce the

antibodies of

patients’ immune

systems to

support people

with less robust

responses. Plasma

from recovered

patients is being

infused into the

seriously ill. But

drugmakers aimto

refine the process,

strengthening the

potency of the

antibodies or

creating artificial

ones that will be

more effective.

MARCH 27 2020 Section:Features Time: 3/202026/ - 18:41 User: alistair.hayes Page Name:BIGPAGE, Part,Page,Edition:USA , 15, 1