Explainer: What is the Covid-19 pill and how does it reduce chance of death?

Covid pill Molnupiravir

Molnupiravir, which, according to interim clinical trial results, can reduce chances of hospitalisation or death by half for Covid-19 patients at risk of severe disease.

Photo credit: Handout | Merck & Co, Inc. | AFP

On Friday October 1, scientists announced positive results on a study designed to find out whether Covid-19 could be treated using a pill — a new oral experimental antiviral drug which has now stirred hope.

The drug, known as Molnupiravir, was developed for the treatment of influenza and has now been found to reduce chances of hospitalisation or death by half for patients at risk of severe disease, according to interim clinical trial results announced on Friday.

Nation writer Elizabeth Merab spoke with two experts, Dr Ahmed Kalebi, consultant pathologist, and Dr Catherine Kyobutungi, executive director at the African Population Health Research Centre (Aphrc), who answered questions about the new drug.

1. What is the difference between this drug and the vaccine?

“A useful analogy is that Molnupiravir acts as a fire extinguisher directly attacking and interfering with fire, extinguishing it, while vaccines are like fire repellents or fire deterrents that need to have been put in place in advance of the fire so that they repel the fire,” explains Dr Kalebi.

Antiviral drugs are different from vaccines in that the antiviral drugs attack and interfere with the virus directly, while vaccines on the other hand are actually designed to stimulate the body’s immune system to produce antibodies and immune T-cells that are able to recognise and attack the virus naturally much like the way immunity from a previous infection enables the body’s immune system to recognise and attack an infectious organism that it was previously exposed to whereby once exposed to the vaccine, the body takes some few weeks to mount the immune response.

The point is that if the body has immunity that is specific to the virus, it can naturally overcome the virus when the virus infects the body before the virus can spread and cause damage in the body, while for someone who has no immunity because they are naïve to the new infection, their body’s immune system can take time to actually respond to the new infection by which time the virus would have multiplied and spread to cause serious damage in terms of severe illness and death.

So antiviral drugs such as Molnupiravir protect the body from serious illness by directly attacking the virus that has infected someone early in the infection and immediately stop the virus from multiplying, while vaccines prepare the body’s natural immune system to be aware, recognise and attack the virus but vaccines need to have been given way before the infection for them to work. The vaccine is not useful for someone who is newly infected and hadn’t been vaccinated previously, while the antiviral drug such as Molnupiravir would act immediately.

2. What makes this drug unique/different compared to available Covid-19 treatments?

Molnupiravir was initially developed and studied to treat influenza virus, and its mechanism of action is almost similar to Remdesivir which also attacks and interferes with the viral RNA.

However, Remdesivir needs to be given as an intravenous infusion and more importantly, Molnupiravir has proven more potent and effective against Covid-19 for it has been shown from clinical trials to reduce mortality from Covid-19 while Remdesivir is yet to have a proven impact on mortality. The impact of Remdesivir is mainly on reducing or slowing the virus which Molnupiravir does in a better way as an oral medication twice a day for 5 days.

Other treatments that have shown some effectiveness on Covid-19 include Regeneron, convalescent plasma and corticosteroids.

“Regeneron for instance, given as an infusion, is quite expensive and has potentially lethal side effects thus it is reserved for only very seriously ill patients. Convalescent plasma is extracted from the blood of patients who have recovered from Covid-19 and works almost like monoclonal antibodies but has an even higher risk of serious side effects with less potency. Corticosteroids such as dexamethasone act by suppressing the body’s immune cells in those who are ill thus minimizing the cytokine storm and the body’s indiscriminatory reaction to the virus which causes the serious ill effect,” says Dr Kalebi.

3. Some Covid-19 treatments like Remdesivir cost as high as Sh450,000 (about $4,500) per course locally. How much will this drug (Molnupiravir) cost or will it be free like the vaccine?

The initial cost of molnupiravir to the US government which has pre-ordered the drug is stated as $700 (about Sh77,350)  for a five-day treatment course.

Although the pricing for African countries like Kenya is not yet clear Dr Kalebi pointed out that it is likely that the market cost would be about “double that at $1,500 (Sh165,750) and if distribution costs plus taxes are added, it may end up retailing at $2,500 (Sh276,250) to $3,000 (Sh331,500) unless a mechanism comes up to subsidise it to the poor markets of developing countries.

4. Experts have called the drug revolutionary despite its high pricing. Why is this the case?

Dr Catherine Kyobutungi explains that it has the potential to reduce the risk of severe Covid-19 disease, hospitalisation and death. If out of the more than 250,000 confirmed cases in Kenya, 25,000 have been hospitalised and more than 5,000 have died; what this drug would have done is reduce the hospitalisations by half to 12,500 and the deaths even further.

“Beyond the huge impact on those who are diagnosed, having this drug means that healthcare systems may not be overwhelmed during peaks of infections and, therefore, even the mitigation measures may have to be relaxed knowing that the system will cope. This also has a huge positive impact on the ability of the healthcare system to deal with other health issues such as those who need ICU care for other reasons and those with common illnesses.

“It revolutionises the treatment because it is highly effective to treat new infection and stop it from progressing to serious illness, and it can be taken orally. No other treatment comes any close to these two factors,” adds Dr Kalebi.

In addition, the drug has been shown to work against three major variants of the virus and due to its biological mechanism, may continue to be effective against future variants – something which is not certain for the current vaccines (because the majority of the vaccines rely on the genetic structure of the virus and this can change significantly in new variants),” Dr Kyobutungi says.

5. Is the drug designed to be administered on the upper arm like the vaccine? If not, how does its administration differ from current treatments and vaccines?

The drug, Dr Kyobutungi an epidemiologist by training noted, is administered orally, meaning by mouth. The patient will swallow one pill twice a day. This has a hugely positive effect on the healthcare system. It only needs someone to prescribe and dispense it. Current treatments require highly specialised people to administer them, in hospital settings and with additional costs in things like gloves, disinfectant, IV tubes etc. in addition to the person prescribing and dispensing.”

6. Would do you say the drug will be a relief for patients with hard-to-find veins?

Patients with inaccessible veins face unique challenges when they are sick for any reason and so this drug will be very useful for such patients if they have early-stage Covid-19 disease. In rare cases, if such patients contract Covid-19 while hospitalised for other reasons, the drug can be given early to prevent the disease from getting worse.

7. If we cannot equitably distribute $10 - 40 Covid vaccines, how we will ensure equity with $700 Molnupiravir?

“This is a valid concern. The Covid-19 pandemic has shown a lack of solidarity in the world whereby rich countries have pre-booked most of the vaccines produced and to be produced in 2021. The booked vaccines are in excess of what can be reasonably expected to be used in those countries. It would not be surprising if the same rich countries with excess vaccine doses bought and hoarded this drug too. The hope is that a different global [production] mechanism is put in place to meet the global demand for the drug and for a differential pricing to make the drug affordable everywhere,” noted Dr Kyobutungi.

8. The same company (Merck) produced Ivermectin. Isn’t Molnupiravir in the same class?

“This has been a common point of discussion. However, Molnupiravir is neither repackaged Ivermectin nor is it in the same class of drugs. The active molecule is different structurally and so is the mechanism of action,” notes Dr Kyobutungi.

Molnupiravir works by disrupting the genetic material of the virus (known as nonsense mutations) such that the virus cannot successfully multiply. Ivermectin on the other hand interferes with the formation of some proteins necessary for the multiplying virus to release new virus particles inside the human cell. Biologically, Molnupiravir is acting much earlier in the virus replication (multiplication) cycle than Ivermectin.


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