“Like previous White House briefings, this one suffered from conflicting messages from the president and his advisers,” Bloomberg News reported today. “Trump, for example, said the malaria drug chloroquine had been approved and could be given to coronavirus patients with a prescription. But an FDA spokesperson clarified mid-press conference that the drug had not been approved for use with Covid-19 patients and FDA chief Stephen Hahn added it was only for use in trials at the moment.”
This “contradicting” of the president was, in fact, not a contradiction at all. Tantalizing but very preliminary data around the world suggest drugs like Hydroxychloroquine and Remdesivir may be effective treatments for reducing the severity of the symptoms. Neither is approved by the FDA for treating patients infected with Coronavirus, but that does not mean treatment is prohibited. The use of an approved drug for an unapproved purpose is infrequent but not uncommon. There is a standard for repurposing existing molecules and, amid a global health crisis, that is a critical element of any holistic effort to stop the spread of this virus.
The FDA’s process for approving new drugs is rigorous. A drug-maker must demonstrate that it can manufacture a new drug safely and reliably in a replicable manner, a hurdle many manufacturers fail to clear. After that, it must be shown that this new drug is safe in the proposed doses and with the prescribed regimen. That’s where clinical testing comes into play; children and the elderly, men and women, the healthy and those with chronic conditions—if the drug is not safe for everyone, establishing its potential toxicities is determined through trials. Finally, a prospective new drug must be shown to be effective. Does it remedy all symptoms of a particular affliction or only some? If these three hurdles are cleared and a drug maker establishes duplicable Chemistry, Manufacturing, and Controls (CMC) standards of which the FDA approves, the drug is then considered for approval.
A repurposed drug already has a CMC and a safety profile on record with the FDA. As long as pre-approved doses and regimen haven’t changed, all that needs to be established in order to use that repurposed drug is its safety and efficacy in its new role. For COVID-19, the benefits of repurposing chloroquine are obvious—it was long ago approved for use in treating Malaria. Antiviral therapies like remdesivir, which is right now being provided to patients in places like Seattle under controlled conditions, has never been approved by the FDA for broad human use. As Dr. Hahn noted, remdesivir is being tested and prescribed for “compassionate use,” but mass distribution would require a substantial short-circuiting of the FDA’s approval process. By contrast, chloroquine in the doses already approved would encounter fewer limitations.
Hydroxychloroquine shows promise. A clinical trial of the drug in France found that the drug substantially shortened the timeline in which people who were infected suffered severe symptoms and, in combination with antibiotics, reduced complications like associated lung infections. After six days of therapy, only one-quarter of the patients who initially tested positive were still infected. What’s more, the drug is relatively inexpensive and not difficult to manufacture. “If clinical data confirm the biological results, the novel coronavirus-associated disease will have become one of the simplest and cheapest to treat and prevent among infectious respiratory diseases,” concluded the researchers who published a February 15 paper in the International Journal of Antimicrobial Agents.
But—and there’s a big “but”—even if this therapy is effective at treating this disease, it will be a long time before anyone has access to it. The FDA probably does not have time for large-scale clinical trials, but chloroquine cannot be approved for use against COVID-19 without testing a representative sample of the population. A disease that has the potential to infect a population so large that it includes almost everyone means the tested sample should be quite big. To be sure, the nation’s regulatory bodies become much less risk-averse in a crisis, and the FDA is no exception. Chloroquine might be subject to a conditional approval based on existing data that falls short of what would normally be needed for full approval, but even so, generating that data will take time. Even if “good clinical practices” are dispensed with, there still must be rigorous and standardized clinical testing in hundreds of patients. Even an expedited process will take many months before the drug reaches the point at which it can be distributed to the public.
The good news is that this process is likely already underway. Pharmaceutical manufacturers are crash-producing research and development programs around existing molecules, including chloroquine. On Wednesday, the Department of Health and Human Services officials revealed, and Bayer confirmed, that the drug-maker had donated 3 million tablets of chloroquine to begin the process. This is not even the end of the beginning of the fight against this terrible new disease, but it is a sign that the fight has begun.