FDA authorizes Pfizers anti-covid pill as omicron surges


Federal regulators Wednesday authorized the first easy-to-take pill to treat covid-19, a drug developed by Pfizer that will help refill the nations medicine cabinet even as the omicron variant, now dominant in much of the country, has thwarted most other options.

Tens of thousands of pill packs of Pfizer's Paxlovid are sitting in a company warehouse in Memphis, ready to be loaded onto trucks and planes in anticipation of the green light from the Food and Drug Administration. But as omicron cases skyrocket nationwide, doctors are expected to quickly burn through that initial supply of the drug, which has shown to be 89% effective at keeping high-risk patients from developing severe illness when given within three days of symptoms starting.

Antiviral pills have been highly anticipated as a potential turning point in the pandemic - a new class of drugs that will help transform life-threatening covid-19 infections into a nuisance. But instead of reinforcing a growing arsenal of drugs, the pills are now urgently needed to help replace workhorse treatments that for more than a year helped keep sick people out of hospitals but are being knocked out by the omicron variant.

Coronavirus cases are spiking across much of the United States, which has seen a 27% rise in new cases in the past week, according to a Washington Post analysis. The seven-day average of cases is 168,981, surpassing the peak of the delta-variant surge in early September. Some states have seen cases soar as the omicron variant has taken hold, according to the Centers for Disease Control and Prevention.

Florida's seven-day average of new daily cases has more than tripled during the past week. According to the CDC, the omicron variant accounted for more than 95% of new cases between Dec. 12 and 18 in the region that includes Florida.

Hospitalizations are also beginning to rise in some areas of the country as health-care systems brace for a winter surge. Indiana and Ohio have the most covid-19 inpatients per capita in the nation. D.C. has experienced the sharpest increase in hospitalizations per capita during the past week, followed by Maryland, New Jersey, New York and Connecticut.

Patrizia Cavazzoni, director of the FDA's Center for Drug Evaluation and Research, said in a statement the new antiviral pill was "a major step forward."

"This authorization provides a new tool to combat COVID-19 at a crucial time in the pandemic as new variants emerge and promises to make antiviral treatment more accessible to patients who are at high risk for progression to severe COVID-19," Cavazzoni said.

The fast-spreading variant is resistant to two key drugs from a different class of medicines known as monoclonal antibodies that have been the backbone of treatments, leaving only a third antibody drug, sotrovimab, which is in severe shortage. Paxlovid - and another antiviral pill from Merck also expected to be authorized shortly - will be used to fill the gaps. A newly authorized monoclonal antibody from AstraZeneca, used to prevent infections in people who do not respond to vaccines, may also remain effective against the omicron variant.

"There's no question that it appears we're in a canoe that is about to go over a significant waterfall," said Bruce Farber, chief of infectious diseases at Northwell Health, a New York health-care system that includes 22 hospitals. Farber said that in November and December, requests for monoclonal antibody treatments had reached 200 or more per day. He said Northwell will run out of doses by the end of the week.

The five-day Pfizer pill regimen could help meet some of that demand, but it is estimated there will be enough medication through the end of the year for only 180,000 patients, and it is unclear how many of those doses are destined for the United States. With coronavirus cases in the United States projected to potentially hit 1 million a day, those pills could be used up quickly, even though they are authorized only for people 12 and older who are at high risk of severe covid-19 because of age or underlying medical conditions.

"The very good news is that we have a product now that has about a 90% efficacy in preventing hospitalization," Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, said Wednesday at a coronavirus task force briefing. "The sobering news is, unfortunately, it is really a quite complicated and complex synthetic process" to manufacture the drug. He added that "we will be working with the company to figure out how we can help alleviate the stress of the long duration that it takes to make it."

Pfizer has been working to scale up to produce 120 million pill packs in 2022, but those doses will not be available all at once. Mike McDermott, Pfizer's president of global supply, said that the current goal is to have about 30 million treatments available by the middle of next year but that the company is looking for ways to speed up and increase production.

The United States has made an advance purchase of 10 million packs of Paxlovid at a cost of about $5.3 billion, along with about 3.1 million treatment courses of the Merck drug, molnupiravir, at a cost of $2.2 billion.

McDermott said that thousands of people are working on Paxlovid but that the complex chemistry involved in creating the pill's active pharmaceutical ingredient means a production run for a batch takes about six to eight months from start to finish. The company creates the active ingredient in giant 10,000- and 20,000-liter tanks, and the process takes a succession of steps, many of which require five to 10 days, with quality checks in between.

"We have experience at this scale - this is not unusual for us," McDermott said. "The urgency is unusual, for sure." He drew a parallel to auto racing, in which pit crews and materials are in place at pit stops to make sure no minutes are lost.

Six months ago, when Pfizer started making Paxlovid before knowing whether it would prove successful, the production goal was to churn out 20 million pill packs in 2022. When the first clinical results showed the drug drastically cut the risk of death or hospitalization, by close to 90%, the company bumped up production to 50 million pill packs. Two weeks later, McDermott said, production was increased to 80 million. When the emergency authorization was announced, Pfizer increased that to 120 million packs.

Each pill pack will contain 30 tablets to be taken over five days, so Pfizer is working to produce 3.6 billion tablets next year. The company is leveraging existing infrastructure in Ireland and Germany to make the key ingredient in the pill and to create the tablets, as well as working with contractors. Pfizer has entered into licensing agreements to allow other companies to produce the pills for lower-income countries.

Much of the excitement about the pills stems from their ease of use. The monoclonal antibodies that have been pillars of treatment require intravenous infusions or injections. Pills taken at home would be far simpler. Side effects included diarrhea, high blood pressure, muscle aches and an impaired sense of taste.

Paxlovid must be given shortly after symptoms develop, so the treatment will depend on people getting tested and receiving results quickly - a potential bottleneck as the omicron surge has created shortages of rapid tests. The clinical trial testing the medicine showed that if given within five days, the drug reduced the risk of hospitalization and death by 88% in people with a risk factor for severe disease, including age or underlying medical conditions.

Paxlovid is a combination of two drugs, one called nirmatrelvir that was designed to interfere with an enzyme the coronavirus uses to make copies of itself. The other drug, ritonavir, is an antiviral that slows down the body's metabolism of the other medication. Ritonavir can react with other commonly taken medications, so the drug's use will have to be managed by physicians and pharmacists. Paxlovid is not recommended for people with severe kidney or liver problems.

The drug was not tested in people who are pregnant, and the label advises people who are pregnant to discuss the possible benefits and risks with a health-care provider. The drug may interfere with birth control pills, and alternative forms of contraception are recommended while taking the medicine.

Ralph Madeb, co-chief medical officer at New York Community Hospital, said antiviral pills could be "revolutionary" but noted their limitations. Because they have to be given early in infection, they are just one part of the treatment tool kit. And they are arriving as hospitals are battling for more tools.

Madeb said that this week, he requested 900 doses of sotrovimab, the antibody that remains effective against the omicron variant. That would be enough, he said, for nine days.

"Demand right now is just infinite," Madeb said. "It's something I've never seen before."