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merck drug won't replace vaccines: alberta scientist

university of alberta professor dr. matthias götte says molnupiravir is another 'tool in the toolbox' in the fight against covid-19.

by maija kappler

oct 5 2021

6 minute read

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merck drug will never replace vaccines, says alberta scientist

molnupiravir was once used to treat hepatitis c. getty

as promising as merck’s experimental covid oral drug is, it shouldn’t be interpreted as an alternative to the covid vaccine, according to a scientist who worked on the research.

dr. matthias götte , a professor of medical microbiology and immunology at the university of alberta, led the team that demonstrated how molnupiravir works at attacking the virus that causes covid in the human body. that research was crucial to merck’s announcement last week that it’s seeking regulatory approval for its covid-fighting drug.

but götte wants to make it clear that molnupiravir is not a replacement for the covid vaccine. “it’s extremely important to have another tool in the toolbox,” he told healthing from his office in edmonton. “this is another tool.”

molnupiravir essentially causes an error in the sars-cov-2 virus. the part of the virus that replicates itself mistakes molnupiravir for part of its viral genome, and when it does that, it adds molnupiravir to the virus it’s replicating, rendering it no longer a threat.

in clinical trials, it reduced the risk of hospitalization or death by 50 per cent. out of 775 unvaccinated patients who had contracted covid, 7.3 per cent who had received the drug were hospitalized 29 days after treatment. in the placebo group, 14.1 per cent were hospitalized, and some had died. and one of the major benefits of molnupiravir is that it can be taken as a drug, unlike previous covid therapies.

götte shared his thoughts on what it was like to research the first oral covid treatment, how it means for hope for countries without access to vaccines and what’s on his research horizon.

when did you start your research on molnupiravir, and what were you looking for?
we started to work at on this particular drug the end of 2020. a little bit of history of my lab: we also studied how remdesivir — which is an antiviral for the treatment of covid-19 — works.

that was at the beginning of the pandemic. then it turned out that remdesivir was given [intravenously or by injection] in hospitals, since it can’t be given earlier in the diseases — but this is often too late. so it was very clear that we need something that could be more easily administered. molnupiravir is an oral antiviral, given in a pill form.

why can’t remdesivir be given in pill form?
this is a property of several drugs, so basically what happens is, if you were to take it as a pill, it would change quickly in the body. so the active form doesn’t reach the cells where it should act. it’s a pharmacology problem.

right now, there’s a lot of effort to develop remdesivir as an oral drug. so the drug stays the same, but [they’re trying to] change the formulation a little bit, so the drug reaches the cells where you want it to reach.

so you were looking for a covid treatment that could be taken as a pill because that would be more accessible to more patients.
yes. basically, the entire research community was aware of this problem. that’s why in the middle of 2020, there were a lot of efforts to develop oral antivirals. around that time [molnupiravir] was already the front runner — it was the most advanced drug. so we thought that this would be a good starting point to look how the drug worked in the body.

had molnupiravir been used before?
in the early 2000s, it was known that what we now call molnupiravir could treat a hepatitis c viral infection, but it was dropped for a number of health reasons. then a few years ago it was resurrected, after the large ebola outbreak [in west africa]. it was recognized that we urgently need these broad spectrum antiviral drugs that don’t [only] work specifically against one virus, but against many viruses. so molnupiravir was then tested, and actually developed as an influenza drug at emory university in the u.s. it was orally available, and it looked good in the preclinical studies.

and then, all of a sudden, came covid. the developers of the drug at emory university, and then, later, ridgeback pharmaceuticals, thought ‘ok, let’s try it again on sars-cov-2.’ they teamed up with labs at vanderbilt university and university of north carolina and tested molnupiravir against covid in cell cultures in animal models. they found anti-viral activity. [the results were] pretty impressive — actually comparable to remdesivir, but the difference was that molnupiravir was orally available.

how did your research advance knowledge about molnupiravir?
these investigators had shown that the way it worked was, it introduced too many mutations in the viral genome, and that’s more than the virus can handle. so you basically generate non-infectious particles — the virus makes too many mistakes. but it was not known how that works at the details level, and this is what we studied.

a biochemical study that explains how a drug is working is very reassuring — before you give a drug to patients, you would like to know how it works. if a patient is asking “how does it work, what are you giving me?” and the clinician doesn’t have an answer, that doesn’t generate trust. and regulatory bodies like health canada or the fda, when they are looking for all the data, they look predominantly at clinical trials. but they also look at things like, how the drug actually works. if we know that, and if everything is aligned consistent through all the data, that makes the case very compelling.

we know molnupiravir has been effective in people who have contracted covid. does it work alongside the vaccine?
molnupiravir was tested in the clinical trial in non-vaccinated people.

there are breakthrough infections — some people, even though they are vaccinated, they get sick. it hasn’t been tested in the clinical trial. but yes, theoretically, it would be possible to treat those people as well.

obviously not 100 per cent [of the population is] vaccinated here, and people get sick, so this is a population where it could work. but we are lucky. we have several vaccines approved here in canada. there are many countries where vaccines are not available to the whole population. in those settings, it is extremely important to have another tool in the toolbox.

we published [our research] in may, when there were roughly 400,000 new cases in india. a lot of people were not vaccinated there, and people were lying on the streets, looking for oxygen bottles. obviously, under these circumstances, molnupiravir could be a useful tool. that’s why merck licensed molnupiravir to five generic companies in india.

researchers are also now looking at what we call post-exposure prophylaxis — so if someone in the household is infected, and you suspect that others could get exposed in the household, if you were to give it prophylactically, it could theoretically prevent infection [or stop an early infection from getting worse].

is there any scenario where molnupiravir could replace vaccines at protecting people from covid?
no. it is very important to know that if these the molnupiravir pills are approved, they would not replace vaccines. they are still the best weapon that we have because they prevent severe disease.

it was being used on unvaccinated people as an emergency measure, when vaccines were not readily available.
yes, exactly.

you are still researching molnupiravir. is it accurate to say you’re looking at whether it could potentially be used against other viruses that could become epidemics?
yes. molnupiravir has shown antiviral activity against several viruses, and we are looking now into other viruses that can cause damage here in north america and elsewhere in the world. every virus has a what i call ‘the engine’ that it uses replicate itself. this drug targets that engine. we want to see if it can have the same effect [it has] against covid.

merck drug won't replace vaccines: alberta scientist

university of alberta professor dr. matthias götte says molnupiravir is another 'tool in the toolbox' in the fight against covid-19.

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merck drug won't replace vaccines: alberta scientist

university of alberta professor dr. matthias götte says molnupiravir is another 'tool in the toolbox' in the fight against covid-19.

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