Can these drugs stop a COVID infection in its tracks? Seattle researchers are at the forefront of new treatments

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Alain Bernier

Seattle Times

At a small research facility nestled near the heart of Seattle’s South Lake Union, Dr. Elizabeth Duke has been testing drugs to arm us in the fight against COVID-19.

Since the start of the pandemic, Duke and other infectious disease experts have conducted trial after trial at UW Medicine and, most recently, at the Fred Hutchinson Cancer Center’s COVID-19 Clinical Research Center, which was developed in October 2020. to treat outpatients with mild to moderate COVID.

Trials take time – and data analysis often takes longer – but as new virus variants emerge and the pandemic continues, the clinic has remained at the forefront of testing many of the the country’s new COVID therapies.

Now, Duke and his team are taking the next big step in the world of COVID drugs: figuring out how to stop viral infections from happening in the first place.

“It’s really exciting,” Duke said. “If a person has been exposed to COVID, we currently have no effective approved treatment for omicron that can prevent an exposed person from continuing to be infected. So that’s the idea here – if we have an infected person in a household, can we treat the other people in the household and prevent them from getting sick? »

While state experts say COVID vaccines are still the best way to prevent infection and serious illness, interest in viral therapeutics has slowly increased, said Dr. Bob Lutz, COVID medical adviser to the State Department of Health.

Duke’s current clinical trial is analyzing the early effects of an existing COVID antiviral called molnupiravir, a pill from Merck that was granted emergency use authorization by the Food and Drug Administration in December. The oral pill has been licensed to treat mild to moderate COVID in high-risk adults 18 and older – although it has not yet been approved as a drug to prevent COVID, or so-called post-exposure prophylaxis.

The results of Duke’s trial could change that and make the pill the first FDA-approved COVID post-exposure prophylaxis available to the general public.

In the United States, the FDA has issued emergency use authorizations for four antiviral drugs and monoclonal antibodies for those with mild to moderate COVID who are at high risk of getting sicker – all of which have significantly boosted national efforts to keep people with COVID out of hospital and avoid serious illness or death. The problem is, local doctors say, many of their colleagues and patients still don’t seem to know them.

“There’s a general lack of awareness among primary providers that these treatments exist,” Duke said, which she attributed partly to changing eligibility requirements and partly to a lack of awareness. education from government agencies.

In Washington state, there is an “ample supply” of COVID drugs that could be distributed to patients who request them, Cassie Sauer, president of the Washington State Hospital Association, said at a press conference this week.

In addition to molnupiravir, doctors can prescribe another – usually more popular – antiviral pill called Paxlovid, developed by Pfizer, which can be given to adults and children 12 and older. Although both have been licensed as drugs to ease COVID symptoms, National Institutes of Health prioritizes Paxlovid after clinical trials show it has an 89% reduction in risk of hospitalization and death , compared to the 30% risk reduction of molnupiravir, Lutz said.

But Lutz urged people to speak with their doctor first because Paxlovid might not be right for some people. Recently, for example, there have been reports in parts of the United States of a “rebound” in COVID symptoms in some people who have taken the five-day Paxlovid course. Other national experts have expressed concerns about potential “interactions” between Paxlovid and other drugs people are taking.

“Remember, 30% isn’t so bad,” Lutz said. “And when you look at all things considered, when you look at the fact that molnupiravir doesn’t have the drug interactions that Paxlovid has…people have to realize that yes, the numbers sound better for Paxlovid, but you can also have more difficulty prescribing this drug.

As of this week, the state has nearly 30,000 doses of Paxlovid and about 25,000 doses of molnupiravir, Lutz said.

Remdesivir, the first COVID treatment to become available in the United States and the only drug with full FDA approval, is also still a “very effective” option, he said. However, the drug cannot be taken at home.

Unlike the oral pills Paxlovid and molnupiravir, remdesivir is an intravenous drug – delivered through a needle or tube inserted into a vein – that must be administered in a health care setting and is difficult to administer in post-exposure scenarios, Duke said.

The state also has a supply of monoclonal antibodies (known as Bebtelovimab) to treat mild to moderate COVID. Monoclonal antibodies also require an IV infusion.

Another drug called Evusheld exists as post-exposure prophylaxis — an exception to Duke’s first trial with molnupiravir — though it’s primarily designed for those who are significantly immunocompromised, not those who are exposed.

“Therapeutics are much easier to get now,” Sauer said at the press conference. “…And this quick action to get these oral therapeutics, especially for high-risk people, could definitely save lives and will definitely help keep you from going to hospital.”

While any antiviral or antibody has the potential to work as a post-exposure preventative, Duke said, only antiviral drugs have been able to track the constant changes in the coronavirus spike protein, the target of antibody treatments. New mutations on the spike protein were one of the main concerns that emerged with the omicron variant.

Antivirals, on the other hand, do not target the spike protein, but rather the virus’ “replication machinery”, Duke said.

“The concept would be the same way we give post-exposure prophylaxis to people when they have been exposed to HIV,” she said. “We give antivirals so that if there’s a virus out there…that would stop it from replicating so it can’t go on to start a bigger chain of infection.”

The relatively rapid development of COVID drugs has got doctors and scientists excited, but more work is needed to make them more accessible, Duke said.

“If your treatment isn’t a pill or something you can self-administer…that means you need contact time and staff at a health facility, and that’s a problem right now,” said said Duke. “… We have staffing gaps at all levels. So if it’s one more thing we need staff for, that’s bad.

Her trial for molnupiravir as a preventative drug is still ongoing and accepting participants through July — hopefully in time to get results by the fall, she said. For those interested in joining the study, Duke is looking for unvaccinated participants who have been exposed to COVID (but not confirmed infection) with someone who has tested positive for the virus within the past five days.

“I am delighted that we have come this far and that we have antivirals available which are effective in preventing people from needing to go to hospital, which also means preventing deaths – and that we now have oral treatments available in pharmacies around the world. country,” Duke said. “All of this is extremely encouraging and hopeful.”

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