[This article was updated late Monday to reflect the response of Henry Ford Health System]
The U.S. Food and Drug Administration has withdrawn its emergency use authorization for the antimalarial drug hydroxychloroquine, once seen by some — including President Trump — as a game-changing treatment for COVID-19 patients.
The decision, outlined in a 15-page document released Monday, addresses a small portion of the drug’s use. Specifically, it pulls back the availability of hydroxychloroquine sulfate, as well as chloroquine phosphate, from the Strategic National Stockpile for use among hospitalized COVID-19 patients.
But the drug still is approved for other off-label uses, and longer-term clinical trials can continue, said Dr. Robert Hyzy, a noted pulmonary and critical care specialist with the University of Michigan.
Hyzy told Bridge Monday that the drug has become so politicized that the public’s understanding of hydroxychloroquine’s effectiveness as a possible treatment for the new coronavirus has swung between two scientifically-unsupported extremes — “from ‘this drug will save me’ to ‘this drug will kill me.’”
Hyzy leads U-M in a multi-center trial launched in April and known as ORCHID, a blinded, placebo-controlled randomized clinical trial which tests hydroxychloroquine’s effectiveness against COVID-19.
Monday’s FDA announcement, he said, “reins in the willy-nilly use” of the drug that began at the height of the pandemic, which was pared following reports of disappointing results and indications the medication could pose cardiac dangers to some patients.
But it does not end scientific studies to more definitively answer questions about hydroxychloroquine’s potential to treat COVID-19, for which there is not yet a vaccine.
Henry Ford Health System confirmed Monday that it will continue its WHIP COVID-19 study, which examines hydroxychloroquine, not as a treatment, but rather as a potential preventative medication. Henry Ford's 3,000-participant trial, announced in April, relies on prescreened, healthy frontline workers and first responders.
While the study will proceed, Dr. Steven Kalkanis, chief executive officer of the Henry Ford Medical Group, told Bridge in an email late Monday that Henry Ford will stop using the medication as a treatment for COVID-19 outside of a clinical trial, despite what he characterized as positive results.
"We have analyzed our data and have seen a significantly improved outcome in a group of COVID-19 patients who received hydroxychloroquine," he wrote, adding that its data is under publication review in a peer-reviewed scientific journal.
"However," he added, "due to today's FDA action, we have suspended the use of hydroxychloroquine outside of a clinical trial. The safety and wellbeing of our patients remains our top priority and we will continue to monitor all available data regarding safety and outcomes and adjust accordingly."
Early promise, caution
Monday’s announcement was hardly surprising to those who have watched the growing body of evidence that called into question the drug’s efficacy and concerns about its safety.
Hydroxychloroquine, sold as a generic or under the brand name Plaquenil, is used to prevent or treat mosquito-carried malaria, as well as certain auto-immune diseases such as lupus and arthritis.
As Bridge reported in May, medical officials in southeast Michigan, the epicenter of the state's COVID-19 outbreak, were split over its use.
“I’m actually surprised it wasn’t withdrawn earlier,” Dr. Dennis Cunningham, medical director of infection control at McLaren Health Care, said Monday. Only a few doctors were still prescribing the drug to COVID-19 patients by the beginning of May; by Monday, McLaren had essentially abandoned its use altogether, he said.
“Not everything that works in a test tube works in real life,” Cunningham said, speaking of the nature of medical research.
In the earliest reports during the coronavirus pandemic, doctors reported that some patients appeared to recover more quickly with the drug. But the profile of hydroxychloroquine skyrocketed in March after Tesla CEO Elon Musk tweeted a reference, and President Trump lauded its potential as a game-changing medication and urged patients to give it a shot.
But scientists quickly also urged caution, and doctors began to report potentially deadly changes to the heart’s rhythm — an alarming side effect so widespread the FDA warned in April against using the drug outside of a closely-monitored hospital setting or clinical trial.
In one of the first high-profile blows to the drug’s promise, a preliminary review of COVID-19 patients at U.S. Veterans Health Administration hospitals found that those who took hydroxychloroquine had higher death rates than patients who didn’t take the drug, and that they were no less likely to end up on a ventilator.
Meanwhile, case reports grew in the FDA Adverse Event Reporting System that raised concern about health problems tied to hydroxychloroquine and related drugs. In some cases, the results were deadly. A review of several studies also raised questions about whether it might actually impair the body’s ability to fight the COVID-19 virus.”
On Monday, the FDA cited reports of “serious cardiac adverse events and other potential serious side effects” as one of the reasons to withdraw the drug.
In its letter announcing the decision, the agency concluded “it is no longer reasonable to believe that the known and potential benefits of [chloroquine phosphate and hydroxychloroquine sulfate] outweigh the known and potential risks associated with the authorized use.”