- Companies are racing to develop a pill that can treat COVID-19.
- Merck has been the first company to announce successful trial results, but more are on their way.
- An effective, easy-to-take treatment could play a big role alongside vaccines.
- See more stories on Insider's business page.
Another COVID-19 breakthrough could be just weeks away, but this time with pills instead of shots.
Two large drugmakers - Pfizer, and Roche - are anticipating late-stage-trial results before the end of the year for experimental antiviral drugs. Merck said Friday that its antiviral pill reduced hospitalization and death, and the company plans to ask the FDA for emergency authorization right away. If successful, these treatments could fill a gap not covered by vaccines: helping already infected people recover faster. They might even be able to stop people from getting sick in the first place.
These oral drugs could change how doctors treat mild and moderate COVID-19 cases and "lower people's risk perception of the pandemic," Matthew Harrison, a Morgan Stanley biotech analyst, wrote in a September 27 research note.
While excitement is building as the pharmaceutical giants launch more studies, don't expect a miracle cure. If these antivirals do work and are safe - which remains to be seen - they're likely to help only in certain circumstances. Scientists working on these drugs say they likely will work best as an early treatment, meaning they won't be of much use to people who are seriously ill.
A simpler, cheaper treatment
COVID-19 pills are an enticing prospect. They're simpler to mass-produce and administer, compared with antibody drugs OK'd to treat COVID-19. The antibody therapies are typically given as an hourlong IV infusion, followed by another hour of monitoring for side effects. The three leading antiviral programs are being tested as 10-pill regimens: two capsules every 12 hours over five days.
The pills are also likely to be cheaper than the antibody infusions, which are free for patients but cost the US government more than $1,000 per dose.
These new drugs could complement vaccines. While the vaccines are highly protective, they also have their limitations. A fraction of people simply refuse to be immunized. Some who get the shot, like those with serious immune-system weaknesses, fail to mount an immune response from the vaccine. And uncertainty lingers for everyone over how well the vaccines stop transmission, as well as how long protection lasts, particularly as the virus keeps mutating.
"We still don't understand how the continued viral evolution is going to impact vaccine efficacy broadly," said Daria Hazuda, the vice president of infectious-disease discovery at Merck who is leading research on a COVID-19 pill. "There's still an important role for antivirals."
Antivirals would be "one more piece of the larger puzzle of solving the COVID problem," said Bernadette Boden-Albala, the director of the public-health program University of California, Irvine, who is not involved with the research.
But Boden-Albala said she was worried the public-health system wouldn't be equipped with widely available rapid testing and an easy way to quickly write and dispense prescriptions for the millions of patients in the US with the virus. The Biden administration isn't working fast enough to build that system now to take full advantage of these drugs if they do work, she said.
"We just have to get the process right - that's been our problem," Boden-Albala said. "We have significant process problems, and the public-health infrastructure is so fragile and needs to be rebuilt."
Merck, Pfizer, and Roche lead the race for a COVID-19 pill
On Friday, Merck announced that interim study results found its antiviral pill halved the risk of hospitalization or death from COVID-19. The company said it plans to ask the FDA for emergency authorization for the pill "as soon as possible."
The New Jersey pharma is developing an antiviral called molnupiravir, which was originally developed as a treatment for the flu. The company licensed the drug in July 2020 from Ridgeback Biotherapeutics, a small Miami biotech. The federal government is betting big on molnupiravir, agreeing in June to buy enough pills to treat 1.7 million people. That $1.2 billion deal is contingent on the Food and Drug Administration authorizing the treatment.
Merck is finishing a study with 1,850 volunteers with mild or moderate COVID-19 who randomly receive molnupiravir or placebo pills. The main goal is to see if fewer patients on molnupiravir are hospitalized or die after 29 days compared with those getting the placebo.
In general, antivirals launch a war against the virus inside our cells. Viruses hijack our cells and convert them into copying machines. Antivirals try to block that replication process. Drugs like molnupiravir, called nucleosides, intentionally insert errors into the copying process, obstructing the virus' quest to replicate.
That process also means antivirals typically are most potent when given earlier on, when replication is limited. In April, Merck stopped researching its drug in hospitalized COVID-19 patients, saying interim data suggested it didn't help those patients.
The Swiss drugmaking giant Roche is also developing a nucleoside called AT-527 with a small Boston biotech called Atea Pharmaceuticals. This drug was being researched as a hepatitis C antiviral before the pandemic broke out. Preliminary results announced in June from a smaller clinical study showed potential for the drug, but upcoming data will be more definitive. Roche expects results before year-end from a study testing AT-527 against a placebo in 1,386 people with mild or moderate COVID-19.
Roche Pharmaceuticals CEO Bill Anderson thinks oral antivirals are the most promising treatments in the industry's pipeline, he said at a September 7 press briefing. Roche's anti-inflammatory drug Actemra, which is authorized in the US to treat hospitalized COVID-19 patients, helps only when patients face severe illness and are struggling to breathe, Anderson said.
"You really want to be able to treat people before they get so sick," he said.
Finally, there's Pfizer's antiviral program, which acts slightly differently by blocking a protease enzyme that plays a key role in the virus' copying process. Pfizer is testing this antiviral in combination with a low dose of ritonavir, another antiviral that slows the breakdown of Pfizer's drug so it lasts longer in the body.
In July, Pfizer started a 3,000-volunteer study of nonhospitalized COVID-19 patients, hoping to reduce the hospitalization and death rates compared with a placebo group. Pfizer wants to have results before the end of the year for that study, which could support a filing for emergency authorization if successful, a company spokesperson told Insider.
Pills to prevent sickness
Other drug developers are betting there will be room for improvement beyond this first wave of oral antivirals. Those companies include Enanta Pharmaceuticals, a small Massachusetts biotech looking to start initial human testing early next year for its own coronavirus pill.
"Just because you have something moving forward that you're going to have data by the end of the year, it doesn't mean it's going to be good data," Enanta CEO Jay Luly told Insider.
There are also clinical trials looking at giving the antivirals even earlier - before people are sick.
Merck and Pfizer are already recruiting volunteers for prophylaxis trials, which are designed to see if their pills will prevent infection and symptomatic disease in the first place. Both studies are recruiting people who live with someone who has symptomatic COVID-19. Roche also plans to start a similar prevention study before year-end.
"We know antivirals, even in these acute respiratory infections, work really well as prophylaxis," Merck's Hazuda said.
HIV-treatment research is the most compelling example of this, Hazuda said; pre-exposure prophylaxis treatment for HIV is up to 99% effective at preventing infection after exposure to the virus. That same concept has held true for flu and respiratory syncytial virus treatments, she added.
Hazuda also said she saw a role for Merck's antiviral beyond COVID-19 in tackling future pandemic threats. Molnupiravir, Hazuda said, has shown activity against a variety of viruses in lab studies, including Ebola. While it has a long way to go from being an effective treatment, it could help prepare against future pathogens, she said.
"We're very excited that it could be something we have readily on hand that could play an important role in future zoonotic transmissions of other coronaviruses, as well as future outbreaks of new strains of influenza virus," she said.