With no proven treatment for the coronavirus, and infections in New York topping 30,000, health experts say the Food and Drug Administration has moved with uncommon speed to authorize New York’s sweeping plan to distribute the drugs through hospital networks.
Planning for such a complex initiative would ordinarily take up to nine months, those experts say. In New York, the U.S. epicenter of the covid-19 pandemic, that timeline has been compressed into three days.
The effort has raised concerns among health experts about safety risks — including the danger of fatal heart arrhythmia and vision loss associated with the drugs — and of raising false hopes in the American public. But Trump’s direct intervention into complex medical issues, as well as New York Gov. Andrew M. Cuomo’s embrace of the strategy, has generated popular excitement about the drugs.
The attention by political leaders also has contributed to runs on supply and hoarding, which New York and other states have tried to block with executive orders restricting prescriptions.
New York will use three medications — hydroxychloroquine and chloroquine in combination with the antibiotic azithromycin — contributed by the Federal Emergency Management Agency and Amneal Pharmaceuticals, the state said. The first wave of patients will receive hydroxychloroquine and azithromycin.
Launching such a plan “is something that normally would have been done in six to nine months and we’re doing it in three or four days,” a New York state health official, who spoke on the condition of anonymity to discuss evolving plans candidly, said in an interview Wednesday.
Patient outcomes from the experiment will be gathered electronically and contribute to an “observational” trial being coordinated by the government, the official said. In an observational trial, which is considered less rigorous than a controlled trial comparing a treatment with a placebo, researchers see if a therapy is safe and effective by gathering and comparing the results in a large database.
In addition to mortality and overall recovery, the study will measure patients’ overall viral load, duration on a ventilator and number of days in the hospital.
The FDA would not comment on any aspects of the massive New York experimental effort, citing its own confidentiality rules.
Ground-level hospital administrators are scrambling to set up the reporting programs so outcome data from patients treated with the drugs can be reported back to the state and federal authorities.
“I have never seen anything like this. It is amazing how the country and everybody can pull together and come up with quick, innovative ways to try to attack it,” said Onisis Stefas, chief pharmacy officer for Northwell Health, which has 22 hospitals in New York and has already been using the anti-malarial drugs to treat patients on a “compassionate-use” basis.
“Everybody’s questioning it, and that’s why these studies need to be done to confirm it,” he said. “There aren’t a lot of other options out there.”
The initiative is freighted with equal parts hope and politics, which some health-care officials and states suggest are eclipsing science.
Nevada, via executive order, this week banned prescriptions of the drugs for the coronavirus until the results of rigorous clinical trials are known.
“We must deal with facts, not fiction,” Nevada’s chief state medical officer, Ishan Azzam, said. Nevada is among states trying to stop runs and hoarding that have depleted supply for people who need the treatments for established uses, including lupus patients. New York’s Cuomo in an executive order has also limited new prescriptions of the anti-malarial drugs to patients with previously approved FDA conditions and to coronavirus patients participating in state-sponsored experiments.
Despite some tantalizing early results, there is scant published evidence that the two anti-malarial drugs will have a benefit for coronavirus patients. More rigorous controlled clinical trials are being conducted in the United States, including in New York and Minnesota, and around the world to prove whether the drugs will work. Anthony S. Fauci, head of the National Institute of Allergy and Infectious Diseases, has repeatedly cautioned, from the same White House lectern as Trump, that indications of benefit so far are anecdotal.
But in the absence of viable alternatives, there has been a global rush to try the drugs. Doctors and hospitals have virtually wiped out U.S. supplies by prescribing them “off label."
The low-cost generic pills have been on the market for decades for malaria, lupus and rheumatoid arthritis. Many experts have said they believe they are relatively safe, although hydroxychloroquine can cause dangerous heart problems and some specialists recommend electrocardiogram screening tests, especially when used in combination with azithromycin. The Mayo Clinic issued a warning Wednesday that doctors need to determine which patients are at risk of potentially fatal arrhythmia before they prescribe the drugs.
“Correctly identifying which patients are most susceptible to this unwanted, tragic side effect and knowing how to safely use these medications is important in neutralizing this threat,” said Michael J. Ackerman, a Mayo Clinic genetic cardiologist. The drugs also can cause permanent eye damage called retinopathy that can lead to vision loss and blindness.
The FDA’s quick action on large-scale observational trials was spurred by Trump’s sudden interest in the anti-malarial drugs. As Fauci and others urged caution, Rep. Mark Meadows (R-N.C.), Trump’s incoming chief of staff, contacted a family doctor in Upstate New York who claims to have used them to successfully treat hundreds of suspected covid-19 cases.
Vladimir “Zev” Zelenko, a doctor in Monroe, N.Y., said in an interview that he was contacted by Meadows after posting an unsolicited video message to Trump on Facebook in which he told the president: “Please advise the country that they should be taking this medication."
The doctor also published an open letter on Google Docs to fellow medics outlining a treatment plan of recommended doses, which was picked up by conservative media.
Zelenko said that over one call and several text messages, Meadows was “very kind and receptive,” and told him his treatment plan was being evaluated at high levels. A person close to Meadows, who like others spoke on the condition of anonymity to candidly discuss internal deliberations, confirmed the two had been in touch this week about the drugs, and said White House experts were evaluating the plan.
Another official said Trump saw Zelenko’s treatment plan on television and flagged it in the White House.
Sean Hannity, the Fox News host and informal Trump adviser, read from Zelenko’s open letter during a telephone conversation with Vice President Pence that aired on his prime-time show Monday evening. Rudolph W. Giuliani, the president’s personal attorney, championed Zelenko’s treatment plan on Twitter the following morning.
Since the start of the coronavirus outbreak, Zelenko, 46, has shared material on Facebook suggesting that the virus may have been deliberately developed by China as a population control device and that its threat was exaggerated by Democrats.
Zelenko acknowledged the drugs could have side effects. “They’re not candy,” he said. “However, this is an unprecedented health crisis, the world’s under attack, this is battlefield medicine.”
Supporters of using anti-malarial drugs against the coronavirus have cited several published studies using small patient groups in France, Japan and China. Some other, equally small analysis, has suggested there is no benefit.
But within a matter of days after Trump expressed his support for the drugs last week, Cuomo announced Sunday that 70,000 doses of hydroxychloroquine and up to 750,000 doses of chloroquine are in the pipeline for New York’s patients.
“There’s a good basis to believe they could work,” Cuomo said Sunday.
Although the scale and urgency of New York’s efforts are new, trying unproven drugs on patients who otherwise might die is common in American health care for cancer and many other ailments including rare diseases. The FDA has the power to grant such “compassionate-use” permission, both on an individual basis and under blanket protocols for larger populations, specialists said.
Drug manufacturer Gilead Sciences has said it is working with the FDA to develop a new, broader program of compassionate use for its experimental antiviral drug remdesivir. If successful, the broader program will allow doctors to get the drug for severely ill coronavirus patients without having to seek individual permission from the company and FDA for each patient.
“On this scale, I think it is unprecedented. I have never seen anything like this,” said Dianne Bourque, a lawyer specializing in FDA rules at the firm Mintz. “We are seeing an explosion of compassionate-use requests and I think that’s a factor of many of our clients trying desperately to find anything that works for desperately ill people right now.
“People are throwing everything at this,” she said.
The FDA is working quickly to accommodate such requests, Bourque added, including issuing compassionate-use approval over the past weekend.
The FDA is clearly reacting to pressure from Trump and the general public, who are clamoring for some sort of treatment, said Alison Bateman-House, a professor of population health at New York University and a specialist in compassionate-use programs. She said the FDA is doing the best it can to balance competing interests in a time of crisis.
“It is very dangerous to take your medical advice from someone who does not actually practice medicine,” she said of Trump’s boosterism statements about the anti-malarial drugs at the White House. Yet, she said, there is some reason to believe the treatments could have a beneficial effect, so large-scale compassionate-use trials could be appropriate.
“The FDA is caught between saying it wants good science, and good processes, and what evidence-based medicine requires,” she said, “and this is what our bosses, the people and the president are telling us they want.
“Sometimes safeguarding the public health … is not what the public wants at a given moment,” Bateman-House said. “They want unfettered access.”