The Morning Dispatch: Pfizer’s Promising New COVID-19 Treatment

Happy Wednesday! If NASA can delay its next trip to the moon by a whole year, it’s probably fine for you to hit the snooze button one more time.

Quick Hits: Today’s Top Stories

• New Hampshire Republican Chris Sununu announced yesterday he will run for a fourth gubernatorial term in 2022 rather than challenge Democratic Sen. Maggie Hassan as many national Republicans had hoped. “I’d rather push myself 120 miles an hour delivering wins for New Hampshire than to slow down, end up on Capitol Hill debating partisan politics without results,” he said. Former Sen. Kelly Ayotte—who lost to Hassan in 2016—also announced Tuesday she would not run for her old seat.

• Wholesale prices in October increased 0.6 percent month-over-month and 8.6 percent year-over-year, according to Producer Price Index data released by the Bureau of Labor Statistics on Tuesday. The 8.6 percent figure ties September for the largest annual increase since at least 2010.

• The January 6 select committee announced Tuesday it had issued subpoenas to 10 additional Trump administration officials, including Stephen Miller, Kayleigh McEnany, John McEntee, and Keith Kellogg. Judge Tanya Chutkan ruled Tuesday that former President Donald Trump cannot block the committee from accessing White House records related to his attempt to overturn the election. Unless another court weighs in, the National Archives is set to begin transferring documents to the committee on Friday. Trump appealed the decision shortly after it was announced.

• General Electric—the industry titan founded in the 1890s that has struggled in recent years—announced Tuesday it plans to split what remains of the business into three public companies by 2024: GE Aviation, GE Healthcare, and GE Energy.

• Vietnam War veteran and former U.S. Senator from Georgia Max Cleland died on Tuesday at the age of 79.

Is Our COVID-19 Toolbox Complete?

Since COVID-19 first began spreading in the United States last spring, public health officials have warned that there won’t be any one silver bullet that brings the pandemic to an end, but rather a suite of tools that, when deployed in combination, will allow society to gradually return to something approaching normalcy. “There isn’t an on/off switch that’ll flip one day,” former Food and Drug Administration Commissioner Scott Gottlieb said just days after the first lockdowns went into effect. “We’ll secure a better toolbox to deal with this threat.”

The number of tools in that toolbox has grown exponentially since March 2020, when our only means of preventing COVID-19 deaths were lockdowns, social distancing, and, eventually, masking. Over the past 20 months, we’ve picked up mass testing, ventilator use, remdesivir, monoclonal antibodies, air filtration systems, and, of course, three incredibly effective vaccines. A month or so ago, we wrote to you about a new oral antiviral drug from Merck, molnupiravir, that would have “huge ramifications” for treating those with COVID-19 because it was shown in clinical trials to reduce the risk of hospitalization or death by up to 50 percent.

Pfizer blew those numbers away late last week in announcing clinical trial data for an oral antiviral drug of its own: PAXLOVID was found to reduce the risk of hospitalization or death by a whopping 89 percent when taken within three days of the onset of COVID-19 symptoms.

That’s an astounding figure, so it’s worth breaking down in detail how it is calculated. Between July 16 and September 29—well after the Delta variant emerged—Pfizer enrolled 1,219 high-risk adults who had contracted COVID-19 in the study. (In a statement provided to The Dispatch, a Pfizer spokeswoman defined “high-risk” in this context as a person being unvaccinated and having “at least one characteristic or underlying medical condition associated with an increased risk of developing severe illness from COVID-19 such as chronic lung disease, hypertension, or diabetes.”) About half of the trial participants (607) were treated with PAXLOVID within five days of symptom onset, and the remainder (612) were given a placebo. After 28 days, nobody treated with the antiviral had died, and only six had been hospitalized. In the control group? Ten deaths and 41 hospitalizations.

In the pharmaceutical company’s earnings call last Tuesday, Pfizer CEO Albert Bourla told investors they should expect initial data on the oral antiviral at some point between Q4 2021 and Q1 2022. It was published on Friday, three days later, because the results were so overwhelming the company discontinued further enrollment in the study to submit them to the FDA as soon as possible.

The primary data still needs to be peer reviewed—and government regulators will certainly require more than just a press release—but physicians and medical experts greeted the news with optimism. “If this drug is as good as they say it is, it will be extremely helpful,” Dr. Isaac Bogoch, a clinical epidemiologist and infectious disease expert at the University of Toronto, told The Dispatch. “We know, sadly, COVID is not going anywhere, and there’s a lot of people who are going to get this infection who have risk factors for severe disease. If it can truly reduce the rate of hospitalization and death by 80 percent, then clearly we could put this drug to good use.”

“The results are pretty impressive, and I think they’re better than most people’s expectations for any antiviral,” added Dr. David Boulware, an infectious disease physician-scientist at the University of Minnesota who has led COVID-19 treatment clinical trials. “This is great news overall.”

Nearly as important as PAXLOVID’s topline efficacy is, like molnupiravir, the manner in which it’s delivered. “Right now, if you get sick and you’re high-risk, the only thing we have to give you are monoclonal antibodies, which require an infusion, which are really expensive, and which are really complicated to get to people,” Dr. Megan Ranney, an emergency physician and professor at Brown University, told The Dispatch last month. With pills, she added, “I can write you a prescription, you can go fill the prescription, and you can take them in the comfort of your own home.”

Pfizer’s antiviral treatment is relatively simple—certainly more so than an intravenous infusion—but it’s slightly more involved than headlines would indicate. In addition to administering patients four PAXLOVID pills per day—two at a time, 12 hours apart—for five days, researchers in the clinical trial also prescribed a “low dose” of the HIV drug ritonavir to slow the breakdown of PAXLOVID in the body so it can remain active for longer periods of time.

“[Prescribers] have a lot of experience with ritonavir, it’s a good drug. There’s just a lot of drug interactions with it,” Bogoch said. “Does that mean that we wouldn’t be able to use this Pfizer medication? No, of course not. We just have to be mindful about the drug interactions, so it’s not like you can give it out like Halloween candy without thinking about it.”

When taken together, PAXLOVID and ritonavir work as protease inhibitors—essentially blocking the activity of an enzyme the SARS-CoV-2 virus requires to replicate. “When the virus binds to the cell, there’s this long protein strand,” Boulware explained. “Then there’s an enzyme that basically chops it up into a number of different pieces that then fold themselves into functional proteins—and that’s the machinery that helps the virus replicate.” If administered early enough, PAXLOVID slows or halts this process before it can really begin, blunting the symptomatic effects of both the virus and the immune system’s response to it.

Because the drug is most effective when administered within days of infection, the success of its deployment (if authorized) will be heavily dependent on logistical systems that have only been built out in some parts of the United States—let alone the world. “Someone has to have timely access to diagnostic testing, and then they have to have timely access to these medications,” Bogoch noted. “If we really want this drug to have a significant impact, that has to be addressed: Accessible diagnostics, low barriers to medical care, and low barriers to accessing this drug.”

Although the pill is not yet authorized anywhere in the world, Bourla told Reuters that Pfizer is already negotiating supply contracts for the pill with 90 different countries, and that—although it is leaning toward pricing the full treatment course at about $700 per person in high-income countries, the cost may be on a sliding scale for low-income countries. “Our goal is that everyone in the world would be able to have it as quickly as possible,” he said. President Biden said over the weekend the United States has already secured millions of doses.

But because distribution is likely to be so uneven—and for countless other reasons—doctors and immunologists continued to stress the importance of vaccination even in the wake of the PAXLOVID results. “Would you rather get stitches over wearing a seat belt?” Dr. Nahid Bhadelia—the founding director of the Center for Emerging Infectious Diseases Policy & Research at Boston University—told STAT News last week. “No. So why would you pick antivirals over a vaccine? You take a vaccine first for protection, and if you’re unfortunate to get a breakthrough infection and you’re high-risk, that’s where an antiviral helps.” Only unvaccinated people were included in the clinical trial data published last week, but Pfizer says a study encompassing vaccinated individuals and breakthrough infections is ongoing.

Last month, we wrote in TMD about the pandemic’s eventual shift to endemic—and what needs to happen for us to get there. In the weeks since, COVID-19 hospitalizations and deaths continued to fall (though new cases have ticked back up slightly in recent days), health regulators authorized vaccines for children ages 5 to 11, and a pharmaceutical giant introduced an incredibly effective antiviral that could be authorized by the end of the year or shortly thereafter. Is the COVID-19 toolbox complete?

“I think that we’re close to the end of the pandemic phase of this virus, and we’re going to enter a more endemic phase,” Gottlieb—now a member of Pfizer’s board—told CBS News over the weekend. “We’ve always said that two of the events that would demarcate the end of this pandemic was being able to vaccinate our children—we’re now able to do that down to age five—and also having a wildly available, orally accessible drug that could treat coronavirus at home to prevent people from hospitalized or dying, and we now have two of those potential pills, one from Pfizer and one from Merck. And there will be more behind that.”

Worth Your Time

• In the wake of Donald Trump’s (ongoing) campaign to discredit and overturn the results of the 2020 election, harassment of election officials has skyrocketed. Seeking to better understand the phenomenon, Reuters reporters Linda So and Jason Szep tracked down nine supporters of the former president who have made threats against secretaries of state, county officials, and voting system company employees, finding seven of them to be totally unrepentant—and proud of their actions. Ross Miller, a real-estate investor in Forsyth County, Georgia “left a Dec. 31 voicemail for Fulton County Elections Director Richard Barron, saying he ‘better run’ and that he’ll be tarred and feathered and executed unless ‘ya’ll do something’ about voter fraud,” they write. “In an interview, Miller acknowledged making the call. ‘I left the message because I’m a patriot, and I’m sick and tired of what’s going on in this country,’ he said. ‘That’s what happens when you commit treason: You get hung.’” So and Szep were met with similar sentiments throughout their reporting. “These cases provide a unique perspective into how people with everyday jobs and lives have become radicalized to the point of terrorizing public officials,” they write. “They are part of a broader campaign of fear waged against frontline workers of American democracy chronicled by Reuters this year. The news organization has documented nearly 800 intimidating messages to election officials in 12 states, including more than 100 that could warrant prosecution, according to legal experts. The examination of the threats also highlights the paralysis of law enforcement in responding to this extraordinary assault on the nation’s electoral machinery.”

• In an essay for American Purpose, Andy Smarick argues that American governance is actually working pretty well—if you know where to look. “The successes in American public life generally happen without fanfare,” he writes. “They are the result of decent people behaving civilly—people more concerned about responsibility, service, and problem-solving than clicks and self-promotion. They are civil servants in Washington agencies, career military, federal prosecutors, and many more. You’ll never know their names, because they don’t seek fame; they do accomplish immeasurable good for our nation. But much of America’s best public service takes place at the state and local levels. That’s where budgets are balanced, transportation projects completed, health systems improved, and libraries renovated. This work is seldom even mentioned by those who lead discussions of public affairs.”

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Toeing the Company Line

• The House on Friday approved about $550 billion in new infrastructure spending over the next five years, and if you’re wondering where all that money is going, be sure to check out yesterday’s Uphill. From bridges and electric vehicles to public transit and electrical grid resiliency, there’s a lot to unpack.

• Sarah and Chris Stirewalt have now had a week to pore over the results of last Tuesday’s elections, and there’s a lot to discuss. “Youngkin certainly deserves credit for whatever behind-the-scenes management he did to keep Trump from stealing the limelight in Virginia, but ultimately it was Trump who tried self-control for a change,” Chris writes in yesterday’s Sweep. “That was very good news for Republicans last week, but certainly does not represent any kind of a strategy that the party can follow into midterms.”

• David’s Tuesday French Press (🔒) focuses on the $8 billion diversity training industry. “As a practical matter, I think right and left make the same mistake about diversity training,” he writes. “They both believe it matters far more than it does. Advocates on the left hope it’s helping change society. Advocates on the right fear it’s changing society. In fact, it does virtually nothing to society at all, except divide us and distract us from the reforms and policies that truly matter.”

Let Us Know

Do you expect skeptics of the COVID vaccines to be similarly reluctant to take COVID antivirals, even after they’re approved by the FDA? Why—or why not?

Reporting by Declan Garvey (@declanpgarvey), Andrew Egger (@EggerDC), Charlotte Lawson (@lawsonreports), Audrey Fahlberg (@AudreyFahlberg), Ryan Brown (@RyanP_Brown), Harvest Prude (@HarvestPrude), and Steve Hayes (@stephenfhayes).