Treatments faltered while vaccines sped ahead
Despite vaccine development, the next few months will bring many sick people. And doctors have few drugs with which to treat them
Nearly a year into the coronavirus pandemic, as thousands of patients are dying every day in the United States and widespread vaccination is still months away, doctors have precious few drugs to fight the virus. A handful of therapies — remdesivir, monoclonal antibodies and the steroid dexamethasone — have improved the care of Covid patients, putting doctors in a better position than they were when the virus surged last spring. But these drugs are not cure-alls and they’re not for everyone, and efforts to re-purpose other drugs, or discover new ones, have not had much success.
The government poured $18.5 billion into vaccines, a strategy that resulted in at least five effective products at record-shattering speed. But its investment in drugs was far smaller, about $8.2 billion, most of which went to just a few candidates, such as monoclonal antibodies. Studies of other drugs were poorly organised. The result was that many promising drugs that could stop the disease early, called antivirals, were neglected. Their trials have stalled, either because researchers couldn’t find enough funding or enough patients to participate.
At the same time, a few drugs have received sustained investment despite disappointing results. There’s now a wealth of evidence that the malaria drugs hydroxychloroquine and chloroquine did not work against Covid. And yet there are still 179 clinical trials with 169,370 patients in which at least some are receiving the drugs, according to the Covid Registry of Off-label & New Agents at the University of Pennsylvania. And the federal government funnelled tens of millions of dollars into an expanded access program for convalescent plasma, infusing almost 100,000 Covid patients before there was any robust evidence that it worked. In January, those trials revealed that, at least for hospitalised patients, it doesn’t.
The lack of centralised coordination meant that many trials for Covid antivirals were doomed from the start — too small and poorly designed to provide useful data, according to Dr. Janet Woodcock, the acting commissioner of the Food and Drug Administration. If the government had instead set up an organised network of hospitals to carry out large trials and quickly share data, researchers would have many more answers now.
“I blame myself to some extent,” said Dr. Woodcock, who has overseen the federal government’s efforts to develop Covid drugs.
She hopes to tame the chaos with a new effort from the Biden administration. In the next couple of months, she said, the government plans to start large and well-organised trials for existing drugs that could be re-purposed to fight Covid-19. “We are actively working on that,” Dr. Woodcock said.
Brand-new antiviral drugs might also help, but only now is the National Institutes of Health putting together a major initiative to develop them, meaning they won’t be ready in time to fight the current pandemic.
“This effort will be unlikely to provide therapeutics in 2021,” Dr. Francis Collins, the head of the N.I.H., said in a statement. “If there is a Covid-24 or Covid-30 coming, we want to be prepared.” Even as the number of cases and deaths have surged around the country, the survival rate of those who are infected has improved significantly. A recent study found that by June, the mortality rates of those hospitalised had dropped to 9 percent from 17 percent at the start of the pandemic, a trend that has been echoed in other studies.
Researchers say the improvement is partly because of the steroid dexamethasone, which boosts survival rates of severely ill patients by tamping down the immune system rather than blocking the virus. Patients may also be seeking care earlier in the course of the illness.
And masks and social distancing may reduce viral exposure. When the new coronavirus emerged as a global threat in early 2020, doctors frantically tried an assortment of existing drugs. But the only way to know if they actually worked was to set up large clinical trials in which some people received placebos, and others took the drug in question.
Getting hundreds or thousands of people into such trials was a tremendous logistical challenge. In early 2020, the N.I.H. narrowed its focus to just a few promising drugs. That support led to the swift authorisation of remdesivir and monoclonal antibodies. Remdesivir, which stops viruses from replicating inside cells, can modestly shorten the time patients need to recover, but has no effect on mortality. Monoclonal antibodies, which stop the virus from entering cells, can be very potent, but only when given before people are sick enough to be hospitalised.
Hundreds of hospitals and universities began their own trials of existing drugs — already deemed safe and widely manufactured — that might also work against the coronavirus. But most of these trials were small and disorganised.
In many cases, researchers have been left on their own to set up trials without the backing of the federal government or pharmaceutical companies. In April, as New York City was in the throes of a Covid surge, Charles Mobbs, a neuroscientist at Icahn School of Medicine at Mount Sinai, heard about some intriguing work in France hinting at the effectiveness of an anti-psychotic drug.
Doctors at French psychiatric hospitals had noticed that relatively few patients became ill with Covid-19 compared with the staff members who cared for them. The researchers speculated that the drugs the patients were taking could be protecting them. One of those drugs, the anti-psychotic chlorpromazine, had been shown in laboratory experiments to prevent the coronavirus from multiplying.
The doctors tried to start a trial of chlorpromazine, but the pandemic ebbed — temporarily, it turned out — in France by the time they were ready. Dr. Mobbs then spent weeks making arrangements for a trial of his own on patients hospitalised at Mount Sinai, only to hit the same wall. “We ran out of patients,” he said.
Pharmaceutical companies are also beginning to fund some trials of repurposed drugs. A study published this week in Science found that a 24-year-old cancer drug called plitidepsin is 27 times more potent than remdesivir at halting the coronavirus in lab experiments. In October, a Spanish drug company called PharmaMar reported promising results from a small safety trial of plitidepsin. Now the company is preparing to start a late-stage trial in Spain to see if the drug works compared with a placebo. Any antivirals that may emerge in 2021 won’t save the lives already lost to Covid-19. But it’s possible that one of those drugs may work against coronavirus pandemics to come.