How Kovid-19 was searched for treatments while vaccination overtook the shed


Nearly a year into the coronavirus epidemic, as thousands of patients are dying every day in the United States and widespread vaccination is still months away, doctors have precious few medicines to fight the virus.

A handful of therapies – Remedisvir, monoclonal antibodies and the steroid dexamethasone – have improved the care of Kovid patients, putting doctors in a better position when those viruses grew last spring. But these drugs are not cure-all and they are not for everyone, and efforts to reuse other drugs or discover new ones have not had much success.

The government imposed $ 18.5 billion in vaccines, a strategy that resulted in at least five effective products coming at a record-shattering pace. But its investment in drugs was about $ 8.2 billion, most of which went to only a few candidates, such as monoclonal antibodies. Studies of other drugs were poorly organized.

As a result, many promising drugs that could prevent the disease early, called antivirals, were neglected. Their tests have stalled, either because researchers did not find enough money or enough patients to participate.

At the same time, some drugs have received continued investment despite disappointing results. There is now evidence that the malarial drugs hydroxychloroquine and chloroquine did not work against Kovid. And there are still 179 clinical trials with 169,370 patients receiving at least some medications, according to the Kovid Registry of Off-Label and New Agents at the University of Pennsylvania. And the federal government funded tens of millions of dollars in an expanded access program for the convocation, nearly 100,000 100,000 Kovid patients before there was any strong evidence that it worked. In January, those tests showed that, at least for hospitalized patients, it is not.

Acting Commissioner of Food and Drug Administration Dr. According to Janet Woodcock, the lack of centralized coordination meant that many tests for Kovid antivirals were doomed from the outset – too small and poorly designed to provide useful data. If the government had established an organized network of hospitals to carry out large tests and quickly share data, researchers would have many more answers right now.

“I blame myself to some extent,” Dr. Said Woodcock, who oversees the federal government’s efforts to develop Kovid drugs.

She hopes to end the chaos with a renewed effort by the Biden administration. In the next few months, she said, the government plans to begin large and well-organized trials for existing drugs that can be rebuilt to fight Kovid-19. “We are actively working on that,” Dr. Woodcock said.

Brand-new antiviral drugs may also help, but now only the National Institutes of Health is taking a major initiative to develop them, meaning they will not be ready in time to fight the current epidemic.

The head of NIH, Drs. “This effort will be unlikely to provide therapeutics in 2021,” Francis Collins said in a statement. “If someone is coming to Kovid-24 or Kovid-30, we want to be prepared.”

Even among all the cases and deaths that have occurred across the country, there has been a significant improvement in the survival rate of those infected. A recent study found that by June, the mortality rate of hospitalized people had fallen from 17 percent to 9 percent at the onset of the epidemic, a trend that has been echoing in other studies. Researchers say the improvement is partly due to the steroid dexamethasone, which increases the survival rate of critically ill patients by lowering the immune system rather than preventing the virus. Patients may seek care earlier during an illness. And masks and social distances can reduce viral exposure.

When the new coronovirus emerged as a global threat in early 2020, doctors attempted to eradicate current drugs. But the only way to know if they actually work is to establish large clinical trials in which some people received a placebo, and others took the drug in question.

Involving hundreds or thousands of people into such trials was a tremendous logical challenge. In early 2020, NIH narrowed its focus to just a few promising drugs. That support led to the rapid authorization of Remedisvir and monoclonal antibodies. Remedsvir, which prevents the virus from replicating inside cells, can reduce the time patients have to recover, but has no effect on mortality. Monoclonal antibodies, which prevent the virus from entering cells, can be very powerful, but only when people are ill enough to be hospitalized.

Hundreds of hospitals and universities began their trials of existing drugs – already considered safe and widely manufactured – that could also work against coroners. But most of these tests were short and cluttered.

In many cases, researchers have been left to set up trials on their own without the support of the federal government or pharmaceutical companies. In April, as New York City embraced the Kovid surge, Charles Mobbs, a neuroscientist at the Icon School of Medicine in Mount Sinai, heard of some intriguing work in France pointing to the effectiveness of an antipsychotic drug.

Doctors at French psychiatric hospitals had observed that relatively few patients became ill with Kovid-19, with staff members caring for them. Researchers speculated that the drugs the patient was taking might be safeguarded. One of those drugs, antipsychotic chlorpromazine, was shown in laboratory experiments to prevent the coronovirus from multiplying.

Doctors tried to start a trial of chlorpromazine, but the epidemic spread – temporarily, until it was ready in France. Dr. Mobbs arranged for weeks to test patients hospitalized in Mount Sinai, only to hit the same wall. “We ran out of patients,” he said.

If Dr. If doctors like mobs can tap into a nationwide network in hospitals, they will be able to find enough patients to run their tests quickly. Those networks exist, but they were not opened to drug-repurchase efforts.

Many scientists suspect that the best time to fight coronavirus is early in an infection, when the virus is multiplying quickly. But it is particularly difficult to recruit trial volunteers who are not in the hospital. Researchers have found a way to properly track people after testing them positive, and to get test drugs delivered to them.

At the University of Kentucky, researchers began such a test in May to test a drug called camostat, which is commonly used to treat inflammation of the pancreas. Scientists thought that it could also serve as a Kovid-19 antiviral because it destroys a protein that the virus relies on to infect human cells. Because camostat comes in a pill form rather than an infusion, it would be especially useful to people like trial volunteers, many of whom lived in remote rural areas.

But researchers have tried to recruit enough participants over the last eight months. He has had trouble finding patients who have recently received a Kovid diagnosis, especially with the unexpected rise and fall of cases.

“It has essentially been a source of delay for all tests around the world,” Dr. Said James Porterfield, an infectious disease physician at the University of Kentucky College of Medicine. Who is leading the trial.

While Drs. While doctors such as Porterfield have struggled to study on their own, some drugs have become sensitized, praised as a treatment-aide despite the lack of evidence.

The first considered panacea was hydroxychloroquine, a drug developed for malaria. Television pundits claim that it had medical powers as President Trump. Instead of starting a large, well-designed test in many hospitals, doctors began a swarm of smaller tests.

“There was no coordination, and no centralized leadership,” said Ilban Schwartz, an infectious disease specialist at the University of Alberta.

Nevertheless, the FDA gave the drug an emergency approval for those hospitalized with Kovid. When large clinical trials finally started producing results, it was discovered that the drug offered no benefit – and could even do harm. The agency withdrew its authorization in June.

Many scientists were left out, looking at the waste of all precious time and resources.

Dr. of the University of Birmingham Michael Sag wrote in the New England Journal of Medicine in November, “The clear, unambiguous and compelling lesson from the hydroxychloroquine story for the medical community and the public is that science and politics do not mix.”

Now there is strong evidence that it works before another drug is becoming popular: the parasite-killing compound ivermectin. Senator Ron Johnson, a Republican from Wisconsin who opted out of hydroxychloroquine in April, held a hearing in December, where Drs. Pierre Corey testified about ivermectin. Dr. Corey, at the time a pulmonary and critical care specialist at Aurora St. Luke’s Medical Center in Milwaukee, called it “effectively a ‘miracle drug against Kovid-19”. So far there are no published results from large-scale clinical trials to support such claims, only small, suggestive ones.

Even if the federal government had established a centralized testing network, as it is now trying to do, scientists would still have encountered some unavoidable obstacles. It takes time to carefully conduct experiments to discover promising drugs and then to confirm that they are indeed worth further investigation.

“In drug development, we are used to 10- to 15-year runways,” said Sumit, a virologist at the Sanford Burnham Prebys Medical Discovery Institute in La Jolla, California. Chanda said.

In February, Dr. Chanda and his colleagues began a different kind of search for the Kovid-19 antiviral. They examined a library of 13,000 drugs, mixing each drug with cells and coronaviruses to see if they prevented infection.

Some drugs proved promising. Researchers tested one of them – a cheap leprosy pill called clofazimine – over several months, used in human lung tissue and hamsters. Clofazimine fights the virus in animals if they acquire it soon after being infected.

Now, almost a year after starting his research, Drs. Chanda is hoping she can find the funding for the hardest part of the drug test: large and randomized clinical trials that can cost millions of dollars. To complete this phase efficiently, researchers almost always need the support of a large company or the federal government, or both – as happened with large clinical trials for new coronavirus virus vaccines.

It is unclear which drug candidates the Biden administration’s new drug-testing effort would support. But if the trials begin within the next few months, it is possible that they may reveal useful data by the end of the year.

Pharmaceutical companies are also funding some trials of reconstituted drugs. A study published in Science this week found that a 24-year-old cancer drug, called plitidepsin, is 27 times more potent than Remedisvir to inhibit coronovirus in laboratory experiments. In October, a Spanish pharmaceutical company called PharmaSpar reported promising results from a small safety test of plitidepsin. Now the company is preparing to start a late-stage trial in Spain to see if the drug works compared to a placebo.

Pharma giant Merck is conducting a large, late-stage test on a pill called molanupirvir, originally developed by Ridgeback Biotherapeutics for influenza, shown to cure fermentation of Kovid-19 has gone. The first results of the trial may be revealed in early March.

Experts are particularly keen to look at this data because molanupirvir may be effective in treating more than just Kovid-19. In April, scientists discovered that the drug could also treat mice infected with other coronaviruses that cause SARS and MERS.

Any antiviral that can emerge in 2021 will not save the already lost lives of Kovid-19. But it is possible that one of those drugs may work against a coronovirus epidemic.

Noah Weiland and Katie Thomas contributed reporting.

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