FDA’s Hahn denies political interference, defends hands-off antibody test policy in interview

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Allowing manufacturers to self-validate COVID-19 serological antibody tests is the best way to get the tests onto the market quickly, FDA Commissioner Stephen Hahn told BioCentury Thursday.

Speaking on a BioCentury This Week -- Special Report podcast, Hahn said steps are being taken by government and the private sector to validate some antibody tests, and users should scrutinize labels and consider conducting their own validation studies.

In a wide-ranging interview, Hahn said working at home and the stress of caring for relatives has impacted FDA’s operations.

He addressed controversies over FDA’s decisions to authorize use of hydroxychloroquine and chloroquine for COVID-19, denying that President Donald Trump has ordered or asked him to make regulatory decisions.

“Not one time has the president asked me or asked me on behalf of the FDA to make a certain decision.”

Stephen Hahn, FDA

Hahn expressed optimism about a public-private partnership that is accelerating vaccine development and suggested that until vaccines are available, antibody therapies are the most promising avenue for treating or preventing COVID-19.

Caveat emptor on antibody tests

Despite growing concerns that personal and public health decisions will be made on the basis of inaccurate test results, Hahn defended FDA’s decision to take a hands-off approach to regulating serological antibody tests.

The risks posed by insufficiently sensitive and specific serological tests are arguably as serious as those posed by faulty diagnostics.

In particular, false positives could lead people to resume normal activities while they are still vulnerable to COVID-19 (see “Navigating the Wild West of COVID-19 Antibody Tests”).

FDA has requested that manufacturers validate tests prior to marketing them, and the agency is working with the National Cancer Institute, CDC and academic labs to validate some tests, but ultimately it is up to buyers and users of serological antibody tests to determine if they are reliable, Hahn said. “We said to the companies that wanted to market [serological tests] that they must validate and meet accuracy and reliability requirements, that they had to notify FDA of the validation. And they also had to label their products, number one, that they weren’t diagnostics, that they were serologic or antibody tests, and that they had not undergone FDA review.”

Hahn acknowledged that some serological test manufacturers “may not have done the careful validation studies that need to be done.”

At the end of the day, however, to get tests into the market quickly FDA is relying on the sophistication of users. “For end users to understand that validation, they need to look into the validation that a company’s done, or do the validation themselves,” Hahn said.

Jury is out on malaria drugs

The FDA commissioner defended the issuance of an Emergency Use Authorization (EUA) for hydroxychloroquine and chloroquine, but said if data from trials demonstrate the drugs are not safe and effective for COVID-19, FDA will terminate the EUA.

“We would absolutely use those data and we would rescind the EUA,” said Hahn.

FDA’s letter authorizing the drugs cites “anecdotal clinical data in case series,” a much lower threshold of evidence than is usually required (see “Debate Over Malaria Drugs for COVID-19 Illustrates White House Conflicts” and “FDA’s Authorization of Malaria Drugs for COVID-19 Looks Like Political Science”).

Although the drugs are approved in the U.S. and could be prescribed off label, the EUA was needed to facilitate imports of versions that haven’t received FDA approval, Hahn said.

Some imports are coming as a result of FDA lifting an import ban on an Indian manufacturer, Ipca Laboratories Ltd. The agency has presented no data to demonstrate that the “cascade of failures” that prompted the import ban has been mitigated.

“We would absolutely use those data and we would rescind the EUA.”

Stephen Hahn, FDA

“We have not approved the use of hydroxychloroquine or chloroquine for the treatment of COVID-19, but we did allow drug into the country” under the EUA, Hahn said.

President Donald Trump, however, has referred to the EUA as an “approval,” and he has touted hydroxychloroquine as a “miracle” treatment for COVID-19.

Trump has also suggested that FDA is acting on his instructions. “I call up Steve, and Steve says we’ll get it done,” the president said at a White House briefing in March.

Hahn denied to BioCentury that Trump had ordered him to authorize use of the drugs or to make any specific decisions. “Not one time has the president asked me or asked me on behalf of the FDA to make a certain decision one way or the other.”

Guidelines released this week by NIH said because of a lack of data supporting efficacy and known toxicities, hydroxychloroquine and chloroquine should not be used to treat COVID-19 outside of a clinical trial.

Repurposed readouts, mAbs on the way

Hahn said he expects readouts in the late spring or early summer on trials of some drugs that have been repurposed for COVID-19.

At least 100 trials of repurposed agents in the clinic are expected to have data readouts by the end of June, according to BioCentury’s COVID-19 Resource Center.

“Where I see the most promise at this point is in the antibody approach as a bridge to a vaccine,” said Hahn, who highlighted three approaches to using antibodies to prevent or treat COVID-19: convalescent serum, hyperimmunoglobulin and mAbs.

FDA is facilitating an expanded access protocol at the Mayo Clinic for convalescent serum derived from patients who have recovered from COVID-19. Center for Devices and Radiological Health (CDRH) Director “Peter Marks and his team has built an amazing network with the Red Cross and with the Mayo Clinic and academic centers to really scale this up in an unprecedented manner,” Hahn said.

“For end users to understand that validation, they need to look into the validation that a company’s done, or do the validation themselves,”

Stephen Hahn, FDA

The Mayo Clinic has treated close to 2,500 people with convalescent serum, he reported.

Convalescent serum can be used to produce hyperimmunoglobulin, “a shot that can be given to Americans both as a treatment and also as a prophylactic,” Hahn said. He added, however, that this would require large-scale donations of convalescent serum so it “doesn’t scale up quite as well as a monoclonal antibodies.”

AbCellera Biologics Inc., Regeneron Pharmaceuticals Inc. (NASDAQ:REGN) and Vir Biotechnology Inc. (NASDAQ:VIR) have announced plans to start mAb studies this summer.

Hahn said he hopes those trials can be completed quickly. The development of a mAb “provides great hope, because if it can be used as a prophylactic, for example, or therapy, it could be available for the fall if we see a recrudescence of the disease.”

Vaccine partnerships

FDA is “partnering with HHS and other groups in the U.S. government to actually put together a public-private partnership around vaccine development,” Hahn told BioCentury.

Referring to the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) public-private partnership, Hahn said FDA and scientists in other government agencies have mapped out the characteristics they’d like to see in a vaccine (see “Collaborating to Clobber COVID-19”).

Hahn praised the collaboration of vaccine manufacturers. “The pharma companies have been very forward leaning,” he said, and “have agreed to share data [and] use common preclinical or pre-human models of testing of the vaccine.”

FDA is being “very flexible” about vaccine testing strategies and is willing to consider human challenge trials, Hahn said.

The agency is also working to ensure manufacturing capacity, including finish-and-fill, and is planning for large-scale deployment, Hahn reported.

He said that he is personally speaking with vaccine manufacturers on a regular basis.

Pharmaceutical companies that manufacture vaccines “stepped up to the plate. There’s a great willingness to share manufacturing capacity to try to ramp up hugely, even if it’s not a vaccine that one company is making” itself, said Hahn.

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