What is Molnupiravir?
Molnupiravir is a medicine used to treat Sars CoV-2 infection. The drug is intended for high-risk patients 18 years of age and older for whom vaccination against the coronavirus may not be effective. This risk group includes, in particular, previously ill, immunocompromised or elderly patients.
The active ingredient directly interferes with the replication process of Sars-CoV-2. In its presence, genetic errors accumulate in the coronavirus genome during each multiplication step. Experts refer to this as “nonsense mutations.”
The higher mutation rate provoked by the drug is fatal for the coronavirus: the more genetic errors there are in the newly copied viral genome, the higher the probability that Sars-CoV-2 will eventually no longer be “functional”. If the viral genetic information is too faulty, the virus can no longer replicate and the Covid-19 disease will subside more quickly.
When will Molnupiravir be approved?
The drug Molnupiravir from Merck, Sharp and Dohme (MSD) and Ridgeback Biotherapeutics has not yet been approved for the European Union. The active ingredient, also known as MK-4482 or EIDD-2801 during the development phase, is currently under review.
How is molnupiravir used?
Molnupiravir treatment should be started as early as possible – usually within three to five days of a confirmed Covid 19 diagnosis. The recommended daily dose is 800 milligrams divided into four individual tablets, each to be taken for five days without interruption.
Because the pivotal study (“MOVe-out”) included only adults, data on use in children and adolescents are not available.
How effective is molnupiravir?
The active ingredient reduces the proportion of high-risk patients requiring hospital treatment for covid-19 – regardless of the viral variant.
Initial efficacy data were provided by the MOVe-out pivotal trial. It took place at 82 centers in 12 countries. It enrolled non-hospitalized patients with confirmed Sars-CoV-2 infection who were at increased risk for a severe course.
These included patients with:
- Severely overweight (obese with a BMI greater than 30).
- Individuals older than 60 years
- Individuals with chronic lung disease (e.g.: COPD)
- Cancer patients
- as well as other pre-diseased persons (e.g..: Diabetes mellitus, coronary heart disease, heart failure, cardiomyopathy, renal insufficiency, etc.).
More recent evaluations in larger patient groups suggest a lower (relative) risk reduction for hospitalization of about 30 percent.
What are the side effects of molnupiravir?
Regulatory documents and initial observational data in the United Kingdom suggest that molnupiravir appears to be a well-tolerated drug. However, a conclusive assessment of the side effect profile is not possible at this time.
Most commonly, participants reported transient mild side effects such as:
- diarrhea (diarrhea)
- general malaise
- Dizziness
- @ headache
Serious side effects did not occur in the pivotal studies. Possible interactions with other drugs are also not known.
Pregnancy and lactation
Molnupiravir should not be taken during pregnancy. Although not conclusively established, animal studies suggest that molnupiravir is probably embryotoxic and thus could harm the unborn child.
Couples should not conceive a child during molnupiravir treatment, including a three-month period after treatment. Whether molnupiravir can pass into breast milk has not been systematically studied. According to expert assessment, breastfeeding should be resumed no earlier than four days after discontinuation of the drug.
Data on long-term safety are not available. Some experts express concerns: at least in laboratory tests with cell series, a mutagenic – i.e. mutagenic – effect has been observed. This could probably also indicate an increased risk of cancer.
However, it is not possible to draw conclusions about the effect in humans from a single cell test in the laboratory. Nevertheless, further studies should dispel these concerns in order to confirm the long-term safety of the active ingredient.
What are the reasons for the safety concerns?
The active ingredient molnupiravir is a so-called “pro-drug”. This means that the initial substance is not yet effective. It is only transformed into an active substance by subsequent metabolic processes in the patient’s body. This is introduced into the viral genome instead of an RNA building block that is actually intended, thus producing defective viral copies.
The fear of some scientists is that instead of a building block inserting itself into the viral RNA, a molecule resembling human DNA could inadvertently be created. Such a spurious molecule could be incorporated into the patient’s genome during cell division. This would – according to the hypothesis – result in mutations in the human genome.
What other questions are currently open?
Some experts fear that widespread use of molnupiravir could increase selection pressure on Sars-CoV-2. This in turn would favor the emergence of new virus variants.
However, the practical application to date does not currently provide any concrete evidence for this assumption either.
