The possibilities of the pill
- Assessing the new oral Covid treatment methods
BY Sumudu Chamara
Amidst opinions for and against the ongoing Covid-19 management efforts, Sri Lanka is moving forward with the vaccination programme. Last week, the health authorities commenced administering the Pfizer-BioNTech vaccine as the booster dose for those who are 60 years or older and are residing in several parts of the country, and this was, after the commencement of the administering of the same for frontline healthcare workers earlier this month.
Even though the booster dose, or a third dose, was thought to be what could provide extra protection that could elevate immunity against Covid-19, the scientific community has come up with newer solutions to curtail deaths and severe complications caused by Covid-19. One such solution is an antiviral medicine called molnupiravir, and the Sri Lankan authorities are also considering using this pill.
Recently, it was reported that the Covid-19 Technical Committee had granted approval for the use of this medicine in Sri Lanka to treat Covid-19. However, the National Medicines Regulatory Authority (NMRA) is yet to grant its approval for this medicine, and even though the authorities, including the Production, Supply, and Regulation of Pharmaceuticals State Minister Prof. Channa Jayasumana expressed hope that a final decision in this regard would be reached last week, it is yet to receive approval to be used in Sri Lanka. For it to receive approval to be used in Sri Lanka, according to Health Ministry officials, either the NMRA has to give permission for the emergency use of this medicine without registration, or the NMRA has to register it and give full clearance, while further studies are required to grant or deny permission for this medicine.
Demand for molnupiravir
However, several countries are considering approving molnupiravir to treat Covid-19, and the UK medicines regulatory bodies have approved it, making the UK the first country to do so. Foreign media outlets report that under the initial stage, the UK has ordered 480,000 courses. In the initial stage, molnupiravir will be given to both vaccinated and unvaccinated Covid-19 infected persons through a national study.
The US has also planned to purchase $ 1.2 billion worth of 1.7 million courses of molnupiravir, and foreign media outlets reported that the country is considering buying 1.4 million more courses.
Molnupiravir (brand name Lagevrio) – manufactured by the Pharmaceutical Companies Merck (known as Merck Sharp and Dohme [MSD] outside the US and Canada), and Ridgeback Biotherapeutics – completed clinical trials just a few months ago, and is awaiting approval from several regulatory authorities to commercially manufacture and distribute this medicine.
Molnupiravir received first regulatory approval globally in the UK on 4 November, even though it is still under review in the European region, while it is awaiting approval from the US Food and Drug Administration (FDA).
Merck, in a press release, said that in addition to those countries, it has entered into supply and purchase agreements for molnupiravir with other governments worldwide, and that it is expecting regulatory authorisation from these governments. In order to increase the availability of this medicine, Merck has also entered into non-exclusive voluntary licensing agreements with established generic manufacturers, and this endeavour will focus on making molnupiravir easily accessible in more than 100 low- and middle-income countries. It is, however, awaiting approval or emergency authorisation by regulatory agencies of those countries.
According to foreign media outlets, Merck has already signed agreements with more than six countries to sell molnupiravir, and the countries that have entered into purchase agreements include Australia, Singapore, and South Korea. According to Reuters, among the countries that have expressed willingness to buy molnupiravir are, France, Indonesia, Italy, Japan, Malaysia, the Philippines, and Thailand.
It is also reported that Bangladesh will be the first country to start selling a generic version of molnupiravir, and it is reported that the producers of molnupiravir are anticipating to produce 10 million courses by 2021.
How does it work; effectiveness
It was originally developed to treat the flu, and it works by replicating the genome (the full set of genetic instructions found in a cell) of the Severe Acute Respiratory Syndrome Corona Virus Two (SARS-CoV-2) which is the virus that causes Covid-19 and is made of ribonucleic acid (RNA), once the virus enters the body. The medicine introduces errors into its genetic code, and it, in turn, prevents the virus from multiplying. Molnupiravir also helps to keep the virus level in the body low, which, in turn, is expected to reduce the severity of the symptoms and complications. The final result is reduced hospitalisations and deaths.
According to the European Medicines Agency (EMA), molnupiravir can be given within five days of the first symptoms to treat adults who are not in need of oxygen support and are at risk of severe disease.
A number of studies have found that molnupiravir can reduce the risk of hospitalisation or death by approximately 50%.
A study conducted by Merck – which involved 775 Covid-19 infected persons who had shown mild to moderate symptoms and had noticed symptoms for the first time within five days – had shown consistent efficacy across different viral variants such as Gamma, Delta, and Mu. Of the participants who were given the medicine, 7.3% had been hospitalised, while no deaths had been reported from among those who were given molnupiravir. However, at the end of the 29-day study period, of those who were given a placebo (a substance given to a person claiming that it is an authentic medicine, usually to study and compare the results given by the actual medicine), 14.1% had been hospitalised and eight persons had died. A total of 53 hospitalisations had been reported from those who were given a placebo. The participants of the said study were non-hospitalised adults, and were from 170 planned locations including Argentina, Brazil, Canada, Chile, Colombia, Egypt, France, Germany, Guatemala, Israel, Italy, Japan, Mexico, the Philippines, Poland, Russia, South Africa, Spain, Sweden, Taiwan, Ukraine, the UK, and the US. The Delta, Gamma, and Mu variants have accounted for nearly 80% of the evaluable cases in the trial, it said, adding that recruitment in Latin America, Europe, and Africa accounted for 55%, 23%, and 15% of the study participants, respectively.
According to studies, to benefit from molnupiravir, it needs to be given to infected persons as soon as symptoms begin to show. This recommendation comes in a context where another study, which involved Covid-19 infected persons who had been hospitalised owing to severe symptoms or complications, did not result in promising results.
As far as side-effects are concerned, according to Merck, there have been no serious side-effects during the clinical trials. However, in a context where molnupiravir works by the process through which the virus replicates its RNA, there are severe concerns as to whether it can result in a similar impact on human’s deoxyribonucleic acid (DNA) or RNA. However, foreign media reports that Merck is in possession of laboratory study data showing that this medicine does not have an impact on humans.
American scientist William A. Haseltine, in an article published in Forbes, expressed concerns about the adverse effects of molnupiravir. He said: “My misgivings are founded on two key concerns. The first is the drug’s potential mutagenicity, and the possibility that its use could lead to birth defects or cancerous tumors. The second is a danger that is far greater and potentially far deadlier; the drug’s potential to supercharge SARS-CoV-2 mutations and unleash a more virulent variant upon the world.”
Even though molnupiravir was mostly given to people who were over 60 years or younger persons who had other conditions that increase the risk of contracting Covid-19 during the clinical trial, there are varying opinions about who should be the target groups for this medicine.
Medicines for Covid-19
Even though vaccines are becoming popular, scientists have started developing several medicines to treat Covid-19, and one of the objectives is giving to the world a Covid-19 treatment easily and at a lower cost. To do that, several medicine producers have come forward.
Molnupiravir is not the only medicine that is being tested to treat Covid-19. US-based medicine producer Pfizer has also started trials of two different antiviral tablets, and the Swiss Company Roche has also commenced working on a similar medication. In addition, Gilead Sciences infused antiviral called remdesivir is also being used to treat Covid-19, mostly after an infected person has been hospitalised.
It is said that Pfizer’s Covid-19 pill PF-07321332 (brand name Paxlovid) is more effective than molnupiravir. Pfizer has halted clinical trials for the same after the results showed that the medicine can reduce the risk of Covid-19 related hospitalisations and deaths by 89%. The Pfizer medicine, known as a protease inhibitor, treats Covid-19 by blocking an enzyme the virus needs in order to multiply. Experts say that when taken alongside a low dose of another antiviral pill called ritonavir, Pfizer’s medicine can stay in the body for longer.
Recently, Pfizer announced that it would permit generic manufacturers to supply the pill to 95 low- and middle-income countries through licencing agreements with the international public health group Medicines Patent Pool (MPP).
According to Reuters, among the countries that have expressed interest to purchase Pfizer’s Covid-19 pill are, Australia, Italy, the UK, the US, South Korea, and Thailand.
However, there is a discourse on the use of the said medicines, particularly who should receive it. While some experts say that unvaccinated people should be given priority, some say that vaccinated people too should receive the same opportunity because the efficacy of the vaccine wanes in a few months.
However, ethicists have opposed giving the Covid-19 pills only to those who have not been vaccinated as of yet or have refused to get vaccinated. The British Medical Journal (BMJ) cited New York University Professor of Bioethics Prof. Arthur Caplan, as saying that refusing a medicine to a vaccinated person with a breakthrough infection while giving it to a vaccine refuser in the next room is impossible to justify. He had further said: “No healthcare provider will comply. The goal of pandemic management is prevention, to prevent transmission. Any step that weakens efforts at prevention that lacks a scientific base is unethical in that it risks undermining support for prevention.”
According to medical experts, the vaccine is still necessary, and will continue to remain the main way of protecting against Covid-19. Also, even though molnupiravir or other similar medicines have been proven to reduce the risk of Covid-19-related hospitalisations or deaths, when it comes to reducing the spread of Covid-19, the vaccines will continue to play a key role.
If approved, molnupiravir would be the first oral medicine permitted to be used for the treatment of Covid-19 at home. One of the reasons why this medicine receives more attention than others which are currently being tested, is because some of the other treatments such as remdesivir are given intravenously (giving a medicine directly into a vein using a needle or a tube), and the ability to purchase conveniently, which according to medical experts, could help people to protect against severe complications caused by Covid-19 with or without getting vaccinated.
Medical professionals also fear that if molnupiravir becomes available, people, especially those who do not wish to get vaccinated, will make the availability of molnupiravir a reason to refuse vaccination. They note however that the pills and the vaccines play roles which cannot be replaced by each other, and therefore, vaccination is still a priority.
From the beginning, medical experts have maintained that getting vaccinated is still the best precaution people can take to be safe from Covid-19. In this context, even if molnupiravir or any other medicine was permitted to be used in Sri Lanka, it will be limited to a measure that prevents serious complications, similar to the vaccines.
It is the people’s responsibility to consider the benefits of different types of measures aimed at protecting against Covid-19, and to make wise choices based on the experts and authorities advice.
Even though there are certain other medicines that are currently being used to help Covid-19 infected persons recover, they are not to be taken without or against the instructions of qualified medical practitioners.