Personal care treatments

Treatments will change the pandemic, but they can’t end it alone

A year after coronavirus vaccines dangled visions of the end of the pandemic, science has once again delivered inspiring results: two antiviral pills that dramatically reduce the risk of hospitalization and death.

The idea that a dreaded infection could soon be treated with a handful of pills is an exciting idea nearly two years after the start of a pandemic that has killed more than 5 million people, at least 770,000 in the United States. . But experts – who are thrilled at the prospect of two powerful new drugs – fear that enthusiasm for the idea of ​​treatments will distract them from their limits and the need to prevent the disease in the first place.

If regulators deem the five-day treatment courses of Pfizer and Merck and its partner Ridgeback Biotherapeutics safe and effective in the coming weeks, as most people expect, the drugs could make the disease much less frightening. The United States has already pre-purchased millions of treatments. The good news comes as an echo of last year, when two remarkably effective vaccines were authorized in the middle of the holiday season as a winter wave of new cases loomed.

But these treatments alone are unlikely to close the book on the coronavirus. Instead, they’ll be a valuable addition to an arsenal the world will need to continue to build and maintain in the long term: vaccines, booster shots, more antiviral pills, anti-virus antibodies designed to stay in people’s bodies. people and quick turnaround times. testing related to treatment options.

Learn more about the COVID-19 pandemic

“It’s a huge part of the toolbox; if we can move everything upstream, instead of trying to treat inpatients with severe, late-stage illness, ”said David Boulware, infectious disease physician in the University of Medicine School of Medicine. Minnesota. ” I am optimistic. In six months, I think things will be fine.

Medicines that can be taken at home to prevent mildly ill people from ending up in hospital will be a turning point. But a major lesson from the pandemic has been that in every corner there are more corners.

Remember the vaccines were better than expected. But more people in the United States, where vaccines are plentiful, died from covid-19 in 2021, after the vaccines became available, than the year before.

Antivirals, too, will be powerful, but they will not be a release card on their own.

Initially, they will be available to people with an increased risk of serious illness due to age or other factors. People will need to recognize their symptoms early, get tested, and start treatment immediately.

Medication is good, but not perfect: Merck and Ridgeback’s molnupiravir halved hospitalizations and deaths in a clinical trial, but that means some people ended up in hospital anyway. Pfizer’s Paxlovid reduced hospitalizations and deaths by 89%, but should be taken within days of symptoms.

And scientists have learned not to underestimate the virus. As soon as treatments become widespread, scientists will watch for signs of resistance.

“There is always a sense of optimism with a new strategy coming up, and I’m also optimistic, this is one more thing that will help us in our fight against this disease,” said Erica Johnson, president of the disease. ‘Infectious Disease Board of the American Board of Internal Medicine and physician at Johns Hopkins Bayview Medical Center. “But I’m also careful because it’s only one strategy, and it only really works if all the other strategies are sound and also work.”

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Virus control strategies, not quick fixes

Carl Dieffenbach, director of the AIDS Division at the National Institutes of Health, has spent decades battling a different virus, overseeing a billion-dollar global research portfolio focused on HIV. Although the long quest for a vaccine has so far not been successful, the disease has been transformed by treatments and prevention strategies. Now he’s trying to apply some of that thinking to covid-19.

No one is willing to set a minimum threshold of necessary treatments for a virus that has been so continually surprising, but when in a hurry Dieffenbach says the coronavirus treatments soon to be reviewed by regulators are “a good start. – not the end.

It is important to build up an arsenal of drugs that use different techniques to stop the virus. One class of drugs can prevent the coronavirus from entering cells, as monoclonal antibodies already in use are designed to do. Another class could interfere with proteases, enzymes that the virus uses to process its proteins, like the drug from Pfizer. Yet a third party could be interfering with a different enzyme that the virus uses to reproduce itself, such as molnupiravir from Merck and Ridgeback.

Dieffenbach believes all three angles of attack will be needed, along with backups for each strategy and cocktails that combine them, to avoid allowing the virus to sneak past the protection offered by any individual treatment.

“Six [treatments] at least. Nine would be better. Twelve would be even better, ”said Dieffenbach. “We need companies to manufacture the drugs on a large scale, as available as aspirin and Tylenol – in metric kilotons.”

Pfizer and Merck both started stepping up their pills before they were given the regulatory green light. Pfizer plans to create 50 million courses of treatment by 2022. Merck plans to have 10 million courses of treatment ready by the end of this year, and more by 2022. The United States has pre-purchased approximately 3.1 million of treatment courses at Merck and 10 million at Pfizer.

The question now worrying many scientists is how the virus will react as these drugs become widely used. Akiko Iwasaki, immunologist at Yale University School of Medicine, sees drug combinations as the future – especially for people with weakened immune systems who may have covid-19 infections simmering for long periods of time. weeks or months, allowing the virus to mutate.

“If we have a combination, an antiviral cocktail, it could protect against the emergence of these mutations,” Iwasaki said.

Iwasaki and her colleagues recently reported a preprint case study of a woman in her 60s whose cancer had weakened her immune system. The patient was ill for six months with a persistent infection with covid-19 and, during her treatment, received a course of remdesivir, an intravenous antiviral drug. At first, her fever disappeared and the virus levels plummeted – until a mutation that made the virus resistant to remdesivir allowed it to reappear.

In this case, the resistant virus that was able to thrive in the presence of remdesivir was not going to take over the world – it was less able to multiply than the original strain. But the case illustrates the risk of the appearance of new variants after treatment.

To protect immunocompromised people, other companies – including AstraZeneca and Adagio Therapeutics – are trying another angle of attack: lab-brewed monoclonal antibodies that were designed to stay in the blood for a long time, on the idea that they could provide a vaccine. long-term protection, similar to a vaccine. Regeneron recently published data showing that its cocktail of monoclonal antibodies, currently approved as a treatment for those infected or recently exposed, remains around 80% effective against symptomatic infections eight months later, strengthening its drug’s case for preventative for people who don’t. respond well to vaccines.

“For us, the vaccination was the jailbreak, it allowed us to live normally,” said Hugh Montgomery, professor of intensive care medicine at University College London leading a trial of the drug AstraZeneca, which has been submitted to US regulators for emergency clearance. “My sister, who has breast cancer and has just had 18 weeks of chemotherapy and cannot produce an antibody response to the vaccine – as we lifted our lockdown, she became a prisoner in her house.”

Instead of a drug or a solution, there will likely be treatment niches – and the market opportunity is not a one-time push; this is what pharmaceutical executives call “sustainable”.

On a recent earnings call, Pfizer chief executive Albert Bourla said he saw a multi-year market for antiviral pills. As long as the world needs vaccines, it will also need treatment.

“As long as you have covid, you will need to immunize and protect, then you will need to treat and save lives,” Bourla said.

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A revolution outside the medicine cabinet

For covid-19 treatments to change the world, the world may also have to change.

Along with medical tools, Dieffenbach is calling for societal change – a new standard in which people with respiratory symptoms test as soon as symptoms appear and start taking medication within three to five days.

“What I am advocating is a fundamental change in approach,” said Dieffenbach. “In the future, we don’t require people to go to the doctor if they feel sick to get tested. There is a quick test you do at home. People are motivated to get a prescription, or already have a prescription so they can start taking it right away. This is where it will have to come to this. “

Even though experts anticipate the arrival of life-saving drugs, they are worried. Will people use the existence of drugs as an excuse to avoid vaccination or boosters? The people who clearly could benefit – those who have avoided the vaccines – will look for tests at the first sign of a sore throat and have access to the drugs quickly enough?

Doctors hope people will find that avoiding the disease completely is the best option. Boulware said a colleague puts it this way: Syphilis can be treated with penicillin. But it’s much better not to get it in the first place.

“It’s almost like applying the right tool for the job at hand. Treatments will play a relief role compared to vaccines, ”said Rajesh Gandhi, infectious disease physician at Massachusetts General Hospital.

The existence of treatments could also trigger the start of a philosophical discussion about how to treat the disease itself. Before covid, people got on flights, went to school, and worked with runny noses and coughs. If people return to their old ways, it can be difficult to identify and treat people early enough in their illness.

“I don’t think we’re just going back to ignoring sick people,” said Larry Corey, virologist and former president of the Fred Hutchinson Cancer Research Center in Seattle. “Come to school or come to work and just assume that no matter what, it won’t hurt you. “

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