Hello, welcome to my channel Medicine with Dr. Moran. If this is your first time visiting I'm
Dr. Keith Moran. Today I want to talk about exciting developments in the treatment of
acute Covid-19 infection. This week the UK has become the first country to approve
the first oral antiviral medication for use in outpatients meaning it's meant to be taken at home
to prevent progression of Covid-19 which might include hospitalization and death. This medication
is currently being reviewed by many countries and given the UK approval it's likely that it's
going to be adopted in many countries. The name of the medication is Molnupiravir. It will go by the
trade name Lageviro. I may not be saying that right. I couldn't find anywhere to talk about
the pronunciation of that particular word. In any event this drug was developed at Emory University
in Atlanta. Which is in the United States and it's being developed by Merk in collaboration
with Ridgeback Biotherapeutics. In the U.S. an emergency use authorization application was sent
to the FDA last month October 11, 2021. A decision has not been made in the U.S. as of November 21,
2021. Now how does this antiviral work? As I showed in my video on how we successfully
fight viruses like Covid-19. This virus just like other viruses replicates itself
inside human cells in order to infect more and more human cells and induce disease.
Antiviral medications often target the replication process and this is how Molnupiravir does. As you
can see on this slide once the virus is inside your cell after attaching to the H2 receptor
its genetic code or RNA then hijacks your cell to generate more of its RNA and then it reassembles
itself many times over. Subsequently it releases more copies of itself from the infected cell.
Molnupiravir is an oral medication that you take 800 milligrams every 12 hours for 5 days.
It comes in a tablet formulation and you take it at home.
It's what we call a pro drug meaning that when it gets absorbed it gets metabolized into the active
drug and this drug then gets incorporated into the viral RNA during replication. When this occurs the
replicated RNA has errors in it which prevents the virus functioning and infecting other cells. Now
the most important part is what clinical evidence do we have that this medication is helpful and in
whom would it be helpful? Now this was the phase 2 trial that was done earlier. This has not yet been
peer reviewed or published. In this study they used different doses of Molnupiravir. They found
that with the 800 milligram twice a day dose in 202 treated patients virus isolation was only 1.9%
versus 16.7% in the placebo group at day three and that difference was statistically significant.
Now by day five no virus was isolated from treated patients. The medication was well tolerated and
there were similar numbers of adverse events in the placebo arm as well as the Molnupiravir
arm. They have recently completed a phase 3 study but the results have not yet been published or
peer reviewed and there are no results on the clinicaltrials.gov website where the trial was
registered. Merck has reported preliminary results of their global phase 3 trial. Now this trial is
a randomized placebo-controlled double-blind multi-site trial of non-hospitalized adult
patients. There's a link to the Merck website and to the results posted by Merck down below
in the description. They call it the MOVe-Out trial. the patients who are enrolled in the study
were not vaccinated and they had at least one risk factor associated with the poor disease outcomes
such as obesity, diabetes, cardiovascular disease, and they had symptom onset within five days prior
to either taking Molnupiravir or placebo. The primary endpoint that was pre-specified
was to look at the percentage of people who ended up hospitalized or died through day 29.
This study was conducted globally as you can see from this particular slide.
At the time of the study Delta, Gamma and MU variants accounted for 80% of the viral strains.
There were 775 patients in total and the plan was to enroll 1,550 patients but the study was
stopped due to the positive results at an interim analysis. The eligibility criteria for getting
into the study was that you had to have laboratory confirmed mild to moderate Covid-19 and you had to
have symptoms as I mentioned for less than five days before getting Molnupiravir or placebo.
All patients again had to have one risk factor associated with poor disease outcome.
And now for the results. First in the Molnupiravir group there were no deaths through day 29.
Which was zero deaths out of 385 patients. This compared to eight deaths in 377
patients who received placebo. Now for hospitalization or death combined there
were 28 patients in the Molnupiravir group out of 385 which was 7.3% compared to 53 out of 377
which is 14.1% in the placebo group now this was highly significant with the p-value of 0.0012.
What that p-value means is that the probability of that difference in the two groups occurring
by chance is 12 in 10,000. So that's really good evidence that there's a difference between the
placebo and the active treatment. Now if you just look at the primary predetermined endpoint which
was hospitalization or death you will see that it was reduced from 14.1% in the placebo arm
down to 7.3% which is a 50 reduction. So if you treat 100 people with this medication you
would prevent hospitalization or death in 7 people which means you have to treat 14 people to prevent
one hospitalization or death and the way I get to the number needed to treat like that of 14
is you take 100 divided by 7. So treating 14 people to prevent one hospitalization or death
in these higher risk people is certainly worthwhile.
What I'm personally intrigued by is the fact that the reduction in deaths in this small study
was 8 deaths in the placebo arm to zero deaths in the Molnupiravir arm. It would be impressive
to find a medication particularly an outpatient oral medication which markedly reduced deaths
to this degree. It's obviously a small trial at this point. We will have to see what the
real world results are as this medication gets to be utilized. It would make sense that the
earlier people start on this medication the more likely hospitalization and death would be reduced
and prevented. You must remember that the number of people in the Molnupiravir group was only 385
patients and so there's always the chance of less frequent side effects that we've not seen so far
as the medication does get released for use to the affected public. Often the benefits
seen in real world situations can be less than the ideal clinical trial situation.
Thus we look forward to real world data on this new medication. Now in terms of side effects these
were seen in 35% of people taking Molnupiravir and 40% in the placebo group. Fewer subjects
discontinued the medication due to an adverse effect in the Molnupiravir group which was 1.3%
discontinuation rate compared to the placebo group that discontinued the medicine at a rate of 3.4%.
Now the UK regulators have gone over the data which is not public at this time other than what
I've shown you today. There is a link down below for additional information about this particular
medication from the UK Medicines Agency. It's very extensive and it includes some contraindications,
interaction with other medications, all ingredients of the medication not just the
pharmaceutically active Molnupiravir, and also pharmacological properties amongst a
number of other things. Merk plans to produce 10 million courses of this treatment this year
more for next year. Many countries have already placed an order for it.
The projected cost is seven hundred dollars U.S. per person for a five-day course. Merck
has already said that they would charge less than this for less wealthy countries. So in summary
today we've got a new drug Molnupiravir which has just been approved in the UK which reduces
hospitalizations and death by 50% with 14 people needing to be treated in order to prevent one
hospitalization or death. The key here is that it needs to be started within five days of symptoms.
The advantages being that it can be taken orally at home. There is hope given that there were no
deaths in the Molnupiravir group in the phase 3 trial that if this can somehow be replicated
or it's markedly reduced then it's certainly going to help many people worldwide. Thanks
for joining me today on Medicine with Dr. Moran. I'm Dr. Keith Moran. Get healthy and stay healthy.