White House Hypes Chloroquine, A Drug Currently In Shortage, As Coronavirus Treatment Hope
Executive Summary
Efficacy trials are under way and one supplier already has said it would restart production to meet the anticipated demand.
The White House and US Food and Drug Administration are ramping up research on an old anti-malarial drug, currently in short supply and carrying a potentially concerning safety profile, as a possible treatment for coronavirus.
President Trump directed the FDA to consider hydroxychloroquine sulfate, which is marketed by Bayer AG as Plaquenil, along with chloroquine phosphate, as potential treatments for coronavirus. FDA Commissioner Stephen Hahn said the agency wants to determine whether “an expanded use approach to that could be done to see if that benefits patients.”
“We want to do that in the setting of a clinical trial, a large pragmatic clinical trial, to actually gather that information and answer the question that needs to be asked and answered,” Hahn said during a 19 March White House Coronavirus Task Force briefing.
Plaquenil is approved for treatment of uncomplicated malaria, acute and chronic rheumatoid arthritis, as well as chronic discoid and systemic lupus erythematosus. But there have been reports that the product has improved symptoms in some coronavirus patients. (Also see "AnGes Takes DNA Vaccine Tack As It Enters Virus R&D Fray" - Scrip, 16 Mar, 2020.) Both Plaquenil and chloroquine phosphate are available in generic formulations.
The FDA said in a statement issued after the briefing that government agencies and academic centers are working to determine whether chloroquine can be used to treat patients with mild-to-moderate coronavirus “to potentially reduce the duration of symptoms, as well as viral shedding, which can help prevent the spread of the disease.” Efficacy studies are underway, the agency added.
A trial expected to begin in May, sponsored by the University of Oxford, is looking at chloroquine in prevention of coronavirus disease in the health care setting is listed in Clinicaltrials.gov. The study has not started recruiting and is expected to be completed in May of 2022. Another study testing combinations of chloroquine with several other drugs in coronavirus started on 15 March. Sponsor Rajavithi Hospital in Bangkok also is not yet recruiting, but expects the study to be completed by 30 November, according to the online database.
Hahn made clear during the briefing that the agency will need data to determine the correct dose and appropriate patients should chloroquine be shown as effective. He also would not speculate about a timeline for when the product could be approved for coronavirus use.
“The president has asked us to expedite this,” he said. “We want to make sure that this is done well and right for the American people.”
Emergency Use Authorization Possible?
Trump was excited about the prospect of deploying the drug as a potential coronavirus treatment, in part because it is already approved and its safety profile is well established. At one point during the briefing he suggested incorrectly that the product already had been approved as a coronavirus treatment.
Trump also highlighted the development of Gilead Sciences Inc.’s nucleotide analogue remdesivir during the briefing, adding, incorrectly, that it was approved and then very close to approval for use against coronavirus. (See sidebar.)
The FDA could grant an emergency use authorization (EUA) for chloroquine to allow more widespread access to the product should the studies appear promising.
Attorney Jeffrey Shapiro, a director at Hyman, Phelps and McNamara, said during a 19 March Food and Drug Law Institute webinar on coronavirus issues that the FDA still would have to determine the risk-benefit profile for coronavirus patients before approving the use.
“Even if you’re taking a known malarial drug and using it for this new unapproved use, there may be different risks than there are when you’re taking it for its labeled use as a malarial drug,” Shapiro said. “So that all has to be assessed by FDA and so the EUA application really needs to address this issue, provide information about what are the benefits, the risks, why the benefits exceed the risk.”
Under its EUA powers, the FDA may specify entities to distribute and administer the drug, as well as require collection and analysis of data on safety and effectiveness, Shapiro said in presentation slides.
John Johnson, counsel at Shook, Hardy and Bacon, added that an EUA could remain in place for years while data is gathered to support a traditional regulatory approval.
Adverse Event Profile May Be Worrisome
Chloroquine also carries a significant safety profile, which may be worrisome for physicians considering it for coronavirus patients.
The Plaquenil label includes warnings of irreversible retinal damage, life-threatening or fatal cardiomyopathy, worsening of psoriasis and porphyria, proximal myopathy and neuropathy, severe hypoglycemia, and in rare cases suicidal behavior.
Labeling recommends physicians use the drug with caution in patients with gastrointestinal, neurological or blood disorders and in those with sensitivity to quinine. Precautions also are recommended for use in patients with hepatic or renal disease.
Chloroquine Shortages In US Ongoing
Some chloroquine and hydroxychloroquine formulations are experiencing shortages, which may limit patient access in the near-term.
The FDA shortage database did not list any current shortages.
But a database maintained by the American Society of Health System Pharmacists indicates that there is only one supplier of chloroquine phosphate tablets, Rising Pharmaceuticals, and that as of 9 March, the 500mg formulation is in shortage, but the 250mg tablet is available.
Rising did not give a reason for the shortage, but said the 500mg tablets were on back order and that a mid-March release date was expected, according to the site.
There are multiple suppliers of hydroxychloroquine sulfate tablets, however as of 19 March the 200mg tablet formulation was in shortage, according to the database.
Mylan NV, one of the manufacturers, said the same day that it had restarted hydroxychloroquine tablet production at its West Virginia facility to deal with a potential increase in demand for the product. The company added that it should be able to begin supplying product by mid-April and API supplies allow it to provide 50m tablets that could treat more than 1.5m patients.
Multiple reports also indicated that Bayer will donate 3m tablets of its chloroquine phosphate for potential use to treat coronavirus.
Stakeholders have warned that the coronavirus pandemic could cause drug shortages, in part because China, where the pandemic originated, is a large hub for drug manufacturing. The FDA has reported only one coronavirus-related shortage and Trump has suggested fears of more widespread problems are unfounded. (Also see "Trump Counts On China To Deliver In The Day Of The Coronavirus" - Pink Sheet, 17 Mar, 2020.)
USP has predicted more shortages are likely as the effects of the Chinese manufacturing slow-down caused by the outbreak work through the supply chain. (Also see "Acyclovir Availability In US May Be Affected By India Export Restrictions" - Pink Sheet, 16 Mar, 2020.)
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Sue Sutter contributed to this report.