By The Washington Post · Christopher Rowland · BUSINESS, HEALTH, SCIENCE-ENVIRONMENT, US-GLOBAL-MARKETS
The drug, called remdesivir, had blocked the Ebola virus in laboratories and in animal experiments. But it did such a bad job extending survival in humans compared to two of the other treatments that researchers decided in August not to try it on any more patients.
Now the drug, created by pharmaceutical giant Gilead Sciences, is being tested in new clinical trials, and global health authorities deem it the most promising of possible treatments for people who are severely ill with the novel coronavirus, which causes the covid-19 disease. Because it is a "broad spectrum'' drug that has been effective against multiple viral targets in the lab and in animals, the strategy could work, experts said.
The drug's journey - from failing to prolong the lives of Ebola patients in sub-Saharan Africa just last year to being rushed into coronavirus clinical trials in China and the United States this year - symbolizes a dire lack of antiviral drugs that can fight emerging infectious threats.
As the outbreak spreads worldwide, a vaccine to prevent infection remains at least a year away. Meanwhile, there is no approved treatment to stop the virus once someone is infected, and the severe and sometimes fatal respiratory distress that afflicts a minority of patients.
The hope is that remdesivir will show better results with the coronavirus than it did with Ebola, which is from a different viral family, officials said. The first trial results could be available in April.
Gilead, the National Institutes of Health and Chinese health authorities are racing to test it on hundreds of people in controlled clinical trials, including a patient who was quarantined in Nebraska after being removed from the Diamond Princess cruise ship. Axios reported this month that Gilead acted so quickly that it did not even wait for required approval by the Food and Drug Administration before it shipped doses to China. Asked to respond, Gilead said it thinks its "limited shipments'' were made in compliance with U.S. law.
"I just hope remdesivir works, because we really need a therapeutic that can intervene in this crisis,'' said Richard Whitley, director of an NIH-funded research effort involving the world's most dangerous viruses.
Gilead did not respond directly about the drug's failure in the Ebola trial. "Covid-19 is a coronavirus that is unrelated to Ebola virus,'' the company said. "Covid-19 is associated with different symptoms, pathology, and a different course of disease.''
Invented by Gilead about a decade ago, remdesivir has been proven to stop certain viruses from replicating in lab experiments and in animals. It has been researched in academic labs in North Carolina and Tennessee with backing from federal taxpayers since 2014, as part of a $37.5 million effort by NIH to find treatments for infectious diseases.
Until Monday, when it fell in a brutal market rout, Gilead's stock price had defied the overall market decline of recent weeks, rising almost 20 percent from Feb. 21 to March 6, on hopes that the drug could provide the first treatment for covid-19.
The lack of treatment helps explain why. The stock price increased 5% on Feb. 24 alone when a top official of the World Health Organization pinned much of the world's hopes for a treatment on the drug.
"There is only one drug right now that we think may have real efficacy, and that's remdesivir," said Bruce Aylward, WHO's assistant director general. Ten days later, RBC Capital Markets gave it only a 50 percent chance of succeeding as a treatment.
The mixed signals have done little to dampen interest. There have been desperate pleas for supplies to treat patients on a "compassionate use'' basis.
Although Gilead leads the pack on treatments, large drug companies such as Merck, Johnson & Johnson and Sanofi, as well as lesser-known companies Regeneron and Moderna, are pursuing coronavirus vaccines and medications, and executives estimate that at least 40 small biotech companies are developing drugs to fight it.
Every time there is a new virus, "we get started, but we don't cross the finish line,'' Julie Gerberding, a former director of the Centers for Disease Control and Prevention who is now the executive vice president and chief patient officer at Merck, said at a news briefing in Washington last week. This time, she said, industry is committed to pushing a vaccine to cross the line for regulatory approval.
"If we don't cross it, it will be because it's scientifically hard,'' she said, "not because of the will or the investment.''
But drug companies also have been accused of not pursuing vaccines and antiviral treatments aggressively because the commercial markets for such drugs are weak.
The potential patient pool for clinical trials dries up once a new infectious outbreak subsides, so investment can be frozen in partly completed projects. And the pool of medical customers for a drug can be short-lived, if a seasonal epidemic quickly disappears, offering little chance to recoup an investment of what could be hundreds of millions of dollars.
Vaccine and treatment development tailed off after outbreaks of the earlier coronavirus cousins, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). The drug industry's lobbying arm, the Pharmaceutical Research and Manufacturers of America (PhRMA), said that at least half of its members have mobilized in various ways to fight the new coronavirus in recent weeks.
"We need to encourage as many shots on goal as possible,'' Stephen J. Ubl, PhRMA's chief executive officer, told reporters.
Government efforts to spur development have produced sporadic progress. In the nearly 20 years since the SARS outbreak, the National Institutes of Health has spent nearly $700 million on research and development efforts around coronavirus, according to a survey by the advocacy group Public Citizen, which criticized the pharmaceutical industry for a "lack of interest that has left us lagging behind.''
Every epidemic presents uncertainty for drug companies, said Amesh Adalja, a senior scholar for the Center for Health Security at Johns Hopkins University.
"You never know how long it's going to last. You never know what the market size is going to be,'' he said. "Every conversation about price is when you're in the middle of an emergency.''
Given the large degree of public financial support, debates are already flaring about how much Gilead should charge for its treatment if it ever makes it to market.
Congress and President Trump authorized up to $3 billion last week for efforts by academic researchers and drug companies to develop vaccines and treatments for coronavirus, part of an $8.3 billion emergency spending bill. The industry successfully opposed efforts by some House Democrats to attach guarantees for affordable prices for vaccines or treatments that result.
Gilead said it is too soon to discuss potential markets, in written responses to The Washington Post.
"We are focused on the potential clinical value that remdesivir may bring to patients and doing our part to respond to the coronavirus outbreak,'' the company said.
Earlier testing of remdesivir has been performed by a partnership of university academics and the National Institutes of Health called the Antiviral Drug Discovery and Development Center, coordinated by the University of Alabama at Birmingham. It is focused on finding treatments for the family of coronaviruses, as well as Ebola, Zika, dengue and chikungunya.
Gilead said it donates free drug samples for the government-funded research of remdesivir and helps design scientific studies and clinical trials. Whitley, an infectious-disease expert who leads the drug development center in Alabama, credited Gilead for staying focused on fighting viral infections despite the poor market incentives.
"Drug companies don't have an interest in emerging infectious diseases,'' he said.
The public should not be excessively discouraged by the negative Ebola results last year, Whitley added. The trial in rural areas of Congo, a conflict zone with rudimentary conditions, was complicated by the fact that remdesivir's correct dosage was unknown, he said. Also, it required a cumbersome daily IV administration, after being reconstituted from a freeze-dried form used for shipping in the uncontrolled climate conditions.
The drug has not been studied in human trials for SARS or MERS, because there are not enough patients, Gilead said.
"The number of clinical MERS infections was limited, with almost exclusive localization in the Kingdom of Saudi Arabia, and there were no SARS infections,'' the company said.
In the new coronavirus outbreak, it said, it is reviewing individual requests from physicians to provide the drug on a "compassionate use'' basis but only to patients who are hospitalized and showing "significant clinical manifestations.''