FDA Withdraws Hydroxychloroquine EUA

16.06.2020 -

The hydroxychlorquine saga refuses to end, but the US Food and Drug Administration (FDA) has moved to end its role in the discussion, apparently at the request of the national emergency response agency Biomedical Advanced Research and Development Authority (BARDA).

On Jun. 15 the US health watchdog revoked its emergency use authorization (EUA) issued on Mar. 28 for the oral formulations of both hydroxychloroquine and chloroquine in the treatment of Covid-19. However, doctors can continue to legally prescribe the drugs off-label, as they can with any drug that is approved for other conditions.

The FDA's emergency use authorization – controversial in some circles, but applauded in others – was narrow in scope, applying only to hospitalized Covid-19 patients and only to drugs donated to the Strategic National Stockpile.

Commenting on what appeared to be a BARDA request to end the EUA, the FDA’s chief scientist, Denise Hinton, said that after reviewing the current research available, the agency had determined the two drugs did not meet the statutory criteria for emergency use authorization.

In a statement, the health agency said it had thus concluded that “it is no longer reasonable to believe that oral formulations of HCQ and CQ may be effective in treating Covid-19, nor is it reasonable to believe that the known and potential benefits of these products outweigh their known and potential risks."

Study discrepancies complicate the picture

Some studies with the two chlorquine formulations have tied these to serious cardiac events as well as other side effects among Covid-19 patients, but one of the most recent, a much discussed paper published in the British medical journal The Lancet, was retracted after a letter signed by 200 clinicians found it to be faulty.

Based on the Lancet’s article describing the study conducted by the Brigham and Women’s Hospital in the US state of Massachusetts, the World Health Organization (WHO) temporarily removed the treatment from its own trials, pending a review of safety data.

As a precaution, Belgium and France halted all trials, and the two countries banned the use of hydroxychloroquine in the coronavirus indication.

Having the EUA in place made it easier for drugs to be donated to the national stockpile administered by BARDA for distribution to coronavirus patients, commentators explained. A number of manufacturers, including Bayer, Novartis and Sanofi, subsequently donated supplies to the government.

FDA commissioner Stephen Hahn had been seen recently as reluctant to end the EUA, defending in an open letter published last month as reflecting an evaluation of the scientific evidence available at that time.

In contrast, former BARDA head Rick Bright said he was abruptly removed from his position in May due to his opposition to the EUA. Bright has since filed a whistleblower suit.

Before the ongoing pandemic, the drug developed by Bayer in the 1930s to treat malaria was prescribed mostly to treat lupus and rheumatoid arthritis. Since US president Donald Trump began promoting it during pandemic TV briefings, hydroxychloroquine has dominated the news.  Trump has also claimed to be taking the drug himself to prevent Covid-19.

According to reports, retail sales of the decades-old drug have soared, due to the lengthening and intensely prominent discussion, while supplies have tightened.

WHO’s indecision under fire again

Following The Lancet’s retraction, the WHO suggested it would resume its global trial with hydroxychloroquine, as its data safety monitoring committee had found no increased risk of death for Covid patients. After the FDA’s announcement, however, the organization said it was still reviewing the data and had not yet decided how to move. This announcement led to more criticism of the health organization’s competence.

The focus of the hydroxychloroquine discussion has now shifted to the data The Lancet study’s authors used to arrive at their safety conclusions. At the center is a small US research company, Surgisphere, and its founder Sapan Desai, a 41-year-old surgeon and entrepreneur. Both The Lancet and the New England Journal of Medicine studies relied on Surgisphere data, which the company has declined to make public.

By its own account, Surgisphere consolidates medical records from hospitals around the world. While declining to comment on the data, Desai told the Bloomberg news agency his firm uses artificial intelligence (AI) and machine learning to automate its processes.

The company has ciaimed to be able to quickly assemble data from hundreds of anonymous hospitals, using numerous electronic medical records systems, under different privacy laws across many countries on multiple continents.  Many scientists see this approach seems

Implausible, noting also that no AI experts were listed on the paper.

Despite the doubts, no one has speculated openly on why the researchers would want to falsify data or stir the hydroxychloroquine pot harder.