REGN Regeneron Pharmaceuticals Inc

By Joseph Walker, Peter Loftus and Jared S. Hopkins 

For drug companies, there is suddenly only one priority: the coronavirus.

More than 140 experimental drug treatment and vaccines for the coronavirus are in development world-wide, most in early stages but including 11 already in clinical trials, according to Informa Pharma Intelligence.

Counting drugs approved for other diseases, there are 254 clinical trials testing treatments or vaccines for the virus, many spearheaded by universities and government research agencies, with hundreds more trials planned. Researchers have squeezed timelines that usually total months into weeks or even days.

"We have never gone so fast with so many resources in such a short time frame," said Paul Stoffels, chief scientific officer of Johnson & Johnson.

Even so, for most treatments and vaccines it will be midsummer before human testing reveals whether they are safe to take, not to mention if they work. J&J is excited about a vaccine prospect but won't be able to start testing it in humans until September. Research progress that is remarkable by usual standards remains far behind the racing virus.

Health officials are warning Americans to brace for the most difficult days this week, with the number of infections in the nation's hardest hit cities expected to peak. More than 1.2 million people have been infected around the globe as of Sunday, according to data compiled by Johns Hopkins University. In the U.S., more than 9,400 people have died from Covid-19, the respiratory disease caused by the coronavirus. The White House projects the U.S. could see 100,000 to 240,000 deaths from Covid-19.

Vaccines to prevent infections and drugs to treat them can't come soon enough. Without them, health authorities have had to rely on containment measures such as travel bans and social distancing, while doctors sometimes give patients unproven agents with the hope they will work.

It usually takes years to develop a new drug treatment or vaccine. After finding prospects, researchers must tweak them to maximize their disease-fighting potency and minimize the risk of unwanted side effects. The compounds must be tested in the lab, in animals and extensively in humans. If they succeed, more time is needed to manufacture large numbers of doses.

The urgent, high-speed search is moving on three fronts. One is to get a vaccine that could provide immunity, allowing a return to normalcy.

Among the farthest along is a vaccine hatched by government researchers and Moderna Inc., a biotechnology company in Cambridge, Mass., for which safety testing in humans has begun. If this and all later clinical studies succeed, it could be ready for use as soon as early next year, researchers say.

In addition, Inovio Pharmaceuticals Inc. of Plymouth Meeting, Pa., said human trials are starting today for an experimental vaccine it is developing. Chinese company CanSino Biologics Inc. and a research arm of the Chinese military have started human testing of a potential vaccine, according to the World Health Organization. In Europe, German company CureVac AG and the University of Oxford are developing vaccines.

Scientists also are exploring whether existing drugs such as hydroxychloroquine for malaria or HIV treatments might work against the coronavirus, and some doctors are already treating patients with hydroxychloroquine. Results from two Chinese studies of Gilead Sciences Inc.'s antiviral remdesivir, previously tested in Ebola, are expected this month. Regeneron Pharmaceuticals Inc, and partner Sanofi SA are testing a rheumatoid arthritis drug against the coronavirus.

On the third front, researchers are hunting for entirely new drugs. Among these efforts, which take longer, are programs to mine the blood of recovered patients for infection-fighting soldiers known as antibodies that can be converted into drugs.

All drug and vaccine research is difficult, but tackling a virus can be especially tricky. Tweaking the immune system, as some drugs and vaccines targeting infectious diseases aim to do, risks sending the immune response into overdrive and making things even worse. It can take researchers several tries to find more powerful agents.

"I think we can find something that, at least, helps people out," said Derek Lowe, a veteran drug researcher. "Whether any of these things work well enough to get people out of their houses, that's another question. Maybe it works well enough to reduce the number of people who go on ventilators."

Johnson & Johnson said it and a division of the Department of Health and Human Services together have committed more than $1 billion of investment to co-fund vaccine research, development, and clinical testing. Other government agencies and universities are also spending on research.

Unlike the race to find cures for cancer or other diseases, there's not necessarily a big payoff at the finish. Companies haven't indicated what they might charge for medicines if they work; some have said they'll provide drugs free or at low cost. Gilead said Saturday it won't charge for 1.5 million doses it has manufactured for clinical trials and emergency uses, or any remainder if the drug is approved.

Scenes from several laboratories show the quest from the inside.

One weekend in January, Kizzmekia Corbett rushed to Building 40 on the National Institutes of Health campus in Bethesda, Md.

Dr. Corbett is a researcher at the National Institute of Allergy and Infectious Diseases, or NIAID. For years, she and colleagues have braced for a pandemic, studying bacteria and viruses that popped up around the world to gain a better understanding when a bad one finally came.

Around Jan. 10, she got a cellphone alert with a vital piece of information about a mysterious virus emerging in China. A consortium of researchers including Chinese scientists had published online the virus's genetic sequence.

That provided its molecular makeup, crucial information needed to craft a vaccine for it. The research also indicated the new virus belonged to a well-known family, the coronaviruses.

Named for the crown-like spikes protruding from their surface, coronaviruses had caused two deadly outbreaks since 2002: severe acute respiratory syndrome, or SARS, and Middle East Respiratory Syndrome, MERS.

Dr. Corbett and a colleague studied the genetic code -- seemingly endless combinations of the letters A, G, C and T, each standing for the chemicals comprising DNA. The sequence looked similar to that of the SARS virus. This meant researchers who had investigated a SARS vaccine, which didn't advance after the epidemic waned, could pursue a similar tack against the new coronavirus.

A vaccine would deliver a disabled spike protein, or the genetic instructions to make a close copy, into the human body. The payload wouldn't infect a person but would train the immune system to recognize and attack the virus. If a vaccinated person encountered the virus, antibodies would spring into action and neutralize it.

"We're lucky that this is a coronavirus because we know what to do. It would be a much worse situation" if the virus belonged to a less-studied family, said Barney Graham, deputy director of the Vaccine Research Center at NIAID.

As the virus spread in Wuhan, China, and then in other countries, U.S. government researchers searched for a partner to help design and make a vaccine. Dr. Graham reached out to one his team previously worked with, at Moderna, which is pioneering a new technology for making vaccines. It uses "messenger" RNA, genetic material that can instruct cells to make proteins able to trigger immune responses.

Like the NIH, Moderna researchers studied the new virus's genetic sequence when it was published. They, too, concluded the spike protein would be the best part to target. So did vaccine hunters at J&J, Sanofi and other companies.

By Monday, Jan. 13, the NIAID and Moderna agreed on a vaccine design. Moderna quickly made a small batch for testing. Dr. Corbett and colleagues started testing it in mice on Feb. 4. Two weeks later, initial results showed it elicited antibodies to coronavirus in the blood.

Success in mice often doesn't mean a similar result in people. Months of testing in humans would be necessary. Moderna retrofitted equipment at its manufacturing plant outside Boston, and by Feb. 25 the NIAID was ready to recruit healthy volunteers. In the past, it has usually taken many months for an experimental vaccine to start human testing after selection of a target.

One morning the following month, George Yancopoulos, chief scientific officer at Regeneron in Tarrytown, N.Y., texted his head of infectious disease research. "Good luck today," he wrote. "The world is sort of maybe depending on you ;)."

It was 8:41 a.m. on Saturday, March 14, the latest in a string of weekends consumed by the company's hunt for a medicine that could knock out the virus in someone it had infected.

Spearheading the efforts was Christos Kyratsous, drug-discovery chief for infectious diseases, who used a rapid-response platform the company had formed after the 2014 Ebola epidemic in West Africa.

His team collaborated with colleagues who tended some special mice with immune systems genetically engineered to have a human-like response to viruses. Because the mice make antibodies indistinguishable from people's, researchers working with the mice can have a compound ready to test in people in months rather than the years it takes to birth a traditional drug from scratch.

The teams had spent weeks collecting antibodies from mice exposed to the coronavirus's spike protein, in hopes that two of the antibody molecules could be combined into a drug able to stop an infection. They also gathered antibodies from the blood of recovered coronavirus patients.

Experiments to see whether these killed the virus in test tubes were being finished up that March Saturday.

"You can come now," Dr. Kyratsous texted Dr. Yancopoulos at 2:45 p.m. Dr. Yancopoulos got off a conference call and walked to the lab. As he entered the lab and saw Dr. Kyratsous smiling, he texted a colleague to bring a bottle of champagne.

Data showed they had found hundreds of antibodies that blocked the virus from entering cells. If it couldn't enter cells, it couldn't replicate. A treatment was still far away -- but now was in sight. The champagne popped open.

"My head was in a rush: 'We've got it,' " Regeneron Chief Executive Leonard Schleifer recalls thinking after his chief scientific officer gave him the details. "The world is starting to fall apart, and if we can just hold on, in that lab, in those tubes, is a cure."

Within days, Regeneron announced it would choose the best two antibodies for a drug in April and would start clinical trials by early summer. It is preparing to manufacture hundreds of thousands of doses a month by the end of the summer.

Getting the drug on the market isn't assured. Clinical trials showing the treatment is both effective and safe could take months. These are the stages where so many medicines fail even after they show promising test-tube and animal results.

Neal Browning was scrolling through his Facebook feed in early March when a friend's post caught his eye.

Mr. Browning is a network engineer at Microsoft Corp. living in the Seattle suburb of Bothell, Wash., not far from one of the country's earliest and worst coronavirus outbreaks. He also lives close to the research center doing a human study of the vaccine that Moderna and the NIAID are developing.

The research center, Kaiser Permanente Washington Health Research Institute, was urgently seeking healthy volunteers to test the experimental vaccine's safety. Mr. Browning's Facebook friend knew of the recruitment effort. After Mr. Browning expressed concern about the virus, the friend texted him details of the trial.

Many medical facilities across the U.S. are seeking people to test the safety of potential coronavirus drugs or vaccines. To make way, they are suspending trials of other medicines, clearing space for coronavirus study subjects and assigning data-entry workers, pharmacists and other staff to deal with the paperwork.

Massachusetts General Hospital, one day after agreeing to test Gilead's remdesivir, walked federal health officials through how it planned to conduct the trial. It did so by phone for safety reasons and because time was short, said Libby Hohmann, who oversees the hospital's clinical-trial effort.

That evening, Dr. Hohmann assembled about a dozen pharmacists, researchers and physicians in a conference room to parcel out trial's tasks, such as collecting blood samples and tracking patients once discharged.

To save time, they skipped typical pretrial exercises such as training the staff in showing hospital doctors and nurses the way to administer the drug. "We're sort of doing those on the fly," Dr. Hohmann said.

Since the trial began March 15, Mass General has enrolled 35 subjects. Among them is a man in his 40s who agreed to be in the study just before nurses inserted a breathing tube down his throat because of respiratory problems from the virus, Dr. Hohmann said. He is now stable, she said.

For the test of Moderna's vaccine, Mr. Browning, the Microsoft engineer, showed up at the Kaiser research institute in downtown Seattle on March 16, becoming only the second volunteer.

It had been just nine weeks since researchers selected a section of the virus's genetic sequence to target, which researchers called the shortest time by at least a month to get a vaccine into the first stage of human testing. Even so, the trial is unlikely to have preliminary results until summer, followed by more testing required that would push the vaccine's availability out about 12 to 18 months, according to the NIAID.

After his shot, Mr. Browning stayed for about an hour so the staff could make sure he didn't have any side effects. He drove home and worked that afternoon helping Microsoft configure network firewalls to accommodate a surge in employees working remotely, until the threat posed by the virus can be quashed.

(END) Dow Jones Newswires

April 06, 2020 12:26 ET (16:26 GMT)

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