Molnupiravir for COVID-19
Mel Herbert, MD
- Molnupiravir is a prodrug of the synthetic nucleoside derivative beta-D-N4hydroxycytidine, a mutagenic ribonucleoside that causes viral RNA polymerase to make errors that causes the virus to make bad copies of itself.
- Merck/Ridgeback Biotherapeutics is the drug manufacturer.
- The study and interim analysis:
- Double blind placebo controlled trial
- Non-hospitalized patients
- Patients enrolled had confirmed SARS-CoV2 infection within 5 days of symptom onset and had at least one high risk feature (diabetes, obesity, age > 60, heart disease, etc)
- Outcome measure was hospitalization or death by day 29
- Results:
- 775 patient enrolled, 170 sites across the world
- Reduction in end-point by 50%
- 1% vs 7.3%
- 28/385 vs. 53/377
- NNT 14.7
- Reduction in death
- 8 deaths on the placebo group vs zero in the treatment group
- 0/385 vs. 8/377
- NNT to prevent one death is approximately 50
- Efficacy appears across the major variants
- Side effects:
- Discontinuation due to adverse effects 1.3% vs. 3.4% with placebo
- Doseage:
- Study stopped, EUA applied for
- US government has already procured 1.7 million doses pending EUA approval
- Company says 10 million doses will be available by end of year
- Post exposure prophylaxis studies ongoing
- What we don’t know
- What is the exact definition of mild-moderate disease?
- Does it work past 5 days?
- What subgroups had best/least efficacy?
- Is it even better given earlier?
- Does it work in low risk patients
- What does this do to immunity and how will it affect vaccination schedules?
- The initial estimated cost per course of treatment will be $700. Will it be available for patients without resources?
- It is also mutagenic to mammalian cells but that is of unclear long term significance
Conclusions: While we still need to see the data, this antiviral appears to be very efficacious against COVID-19. If the reduction in death is reproducible and robust, this represents a significant new tool in our fight against the pandemic.
References:
Press Release: https://www.merck.com/news/merck-and-ridgebacks-investigational-oral-antiviral-molnupiravir-reduced-the-risk-of-hospitalization-or-death-by-approximately-50-percent-compared-to-placebo-for-patients-with-mild-or-moderat/
Medical Letter Review: https://secure.medicalletter.org/w5040a
Information on pricing from VOX article: https://www.vox.com/22704265/merck-covid-19-antiviral-pill-molnupiravir-treatment-drug
Mutagenicity: https://pubmed.ncbi.nlm.nih.gov/33961695/
Ian L. - October 6, 2021 4:18 PM
A press release by Gilead on September 22 2021 reported that intravenous Remdesivir for three days given early within four days of diagnosis in the infective phase to 279 patients as compared to 279 in placebo at risk of progression reduced hospital admission and death by 87 % . Hospital Admission in the IV remdesivir group was 0.7 % in the placebo group 5.3 % . With regards to death at day 28 it was 4/246{1.6 %] in the treated group and 21/252(8.3 ) in the placebo group . With acute viral illness very early ,prodromal and post exposure treatment seems to be very important as in Hsimplex H zoster Influenza and HIV . Also be interested to know the analysis of monoclonal antibody therapy thus far in the USA .
Silver Surfer - December 28, 2021 9:02 PM
Now that study data have been published, one can see significant flaws that suggest no benefit, or at least no proof of benefit, to Molnupiravir in early covid infection.
DOI: 10.1056/NEJMoa2116044
The study concludes a reduction in hospitalization or death from 9.7% to 6.8%, but placebo and control groups had important differences at baseline that favor the treatment arm. The placebo group had higher percentages of men, DM, age >= 50, age >= 60, chronic kidney disease, active cancer, and COPD.