FDA revokes authorization for key anti-COVID drug, a blow for vulnerable Americans

The Food and Drug Administration has withdrawn its preliminary support for the use of Evusheld, a drug that was once a valuable tool in preventing immune-compromised patients from developing serious illness from COVID-19.

With new viral variants getting better at defeating Evusheld, the FDA said the biologic drug should be phased out.

The FDA decision marks — at least for now — the end of a drug that had helped restore some normalcy to the lives of cancer patients, transplant recipients and others who either couldn’t be vaccinated against COVID-19 or whose immune systems had failed to respond well to it Vaccination. Up to 3% of the US population – 7.2 million adults – is believed to have immune deficiencies that put them at risk of becoming seriously ill or dying if they contract the pandemic virus.

“It’s a really sad time,” said Dr. Camille Kotton, an infectious disease physician at Massachusetts General Hospital who cares for people with compromised immune systems. For her patients, she said, “it was like being told the seat belts in their car no longer worked and we can’t replace them with anything.”

In recent months, nine new subvariants of the dominant Omicron tribe have proven capable of bypassing Evusheld’s defenses. Taken together, these subvariants now account for more than 90% of the SARS-CoV-2 coronavirus samples circulating in the United States, according to the Centers for Disease Control and Prevention.

The Result: After 15 months in the nation’s armory against COVID-19, a drug that US taxpayers spent at least $1.58 billion to develop and manufacture has become largely ineffective. But the FDA said its approval for the drug would be reinstated if at least 10% of circulating coronavirus samples were susceptible to it in the future.

Evusheld is the trade name of a medicine made by AstraZeneca that combines two monoclonal antibodies, tixagevimab and cilgavimab. In a statement on Friday, the Anglo-Swedish pharmaceutical giant said it was testing the safety and effectiveness of a new antibody drug to protect people with compromised immune systems, which it plans to launch in the second half of 2023.

When Evusheld became available to patients just over a year ago, his protection allowed many immunocompromised patients to emerge from isolation for the first time since the pandemic began.

It was to be given to patients who needed it every six months. But some never got their first shot, and many didn’t get their second, before changes in the coronavirus rendered it ineffective.

“We mourn the official demise of a really good tool,” said Kotton.

Many doctors had already accepted that Evusheld’s time was over.

Physicians at UCLA Medical Center and its satellites stopped giving it to their transplant and chemotherapy patients in December. By this time, the Omicron subvariant known as BQ.1.1, which had found a way to bypass Evusheld’s protection, became dominant in Southern California.

“It’s unfortunate,” said Dr. Tara Vijayan, UCLA Physician of Infectious Diseases. But, she added, “we were surprised the FDA waited this long to pull it.”

Thanks to the relentless rate at which new coronavirus variants have emerged, a number of COVID-19 drugs based on bioengineered monoclonal antibodies have become obsolete.

Since November 2020, when the first such treatments for COVID-19 received interim FDA support, genetic changes in the coronavirus have rendered six useless. It started with the emergence of the Delta variant in March 2021, and the arrival of the Omicron variant – itself fragmented into 18 subvariants – nine months later wiped out the rest.

As of April 2021, the FDA has withdrawn its emergency use approval for all monoclonal antibody treatments used as therapies for COVID-19, with the exception of tocilizumab, which continues to be used in some hospitalized patients.

As UCLA doctors watched one by one as their monoclonal antibody therapies failed, “we always advised some caution,” said Vijayan, the health system’s medical director for adult antimicrobial management. “We have always waited for the variants and the associated resistance.”

The virus’ triumph over these sophisticated therapies has left all COVID-19 patients with a dwindling supply of rescue drugs. But for patients with weakened immunity, the situation is even worse.

The incessant shapeshifting of the virus has completely destroyed the stockpile of effective medicines that can save them from serious illness or death from COVID-19. Many cannot take the antiviral Paxlovid because it interacts with their other medications. That leaves them with the less effective antiviral molnupiravir and the drug remdesivir, which has to be infused daily, usually in a hospital, for three days.

The shortage of drugs for patients with compromised immune systems has reignited interest in convalescent plasma, an old-school version of antibody therapy first explored in the early days of the pandemic. As COVID-19 therapies have waned for these fragile patients, several medical societies have recommended a return to using blood products sourced from previously infected patients who have recovered.

A recently published systematic review of clinical trials suggests that convalescent plasma could help prevent deaths in hospitalized COVID-19 patients with compromised immunity. And a UK clinical trial is now testing the use of “vax plasma” – plasma from vaccinated people who have had breakthrough infections and then recovered.