SINGAPORE, April 22 — The prospect of popping a pill in order to treat Covid-19 made a couple of advances on Tuesday (April 19). First, one such drug, molnupiravir, was granted interim authorisation here by the Health Sciences Authority (HSA) and second, a pilot programme to prescribe another drug, paxlovid, to patients was expanded to 16 more clinics.
Molnupiravir is marketed as Lagevrio and manufactured by pharmaceutical company MSD. Paxlovid, made by Pfizer, is the only other oral Covid-19 medicine granted interim approval by HSA on Jan 31.
Infectious diseases experts said that although molnupiravir’s efficacy of 30 per cent is lower than an October 2021 interim report that put the rate at 50 per cent, the new drug is a much-needed alternative to reduce the number of Covid-19 patients progressing to hospitalisation or death.
TODAY explains what molnupiravir is, how it fares compared to alternative treatments available, and how having a new pill can help Singapore’s recovery from Covid-19.
What do we know about molnupiravir?
In consultation with its Medicines Advisory Committee, HSA granted the drug interim authorisation under the Pandemic Special Access Route, which allows early access to critical new vaccines, medicines and medical devices during a pandemic.
However, this also means that MSD is required to continuously send updated clinical data from studies, which HSA will review. The authority can also terminate molnupiravir’s authorisation at any time should results determine that the risks of treating the Sars-CoV-2 coronavirus outweigh the benefits.
For Dr Leong Hoe Nam, an infectious disease expert from Rophi Clinic, having constant reviews of MSD’s data is important given that so far, there has been no explanation for the drug’s reduced level of efficacy.
In a combined second- and third-phase study, molnupiravir was able to reduce the risk of hospitalisation or death in Covid-19 patients with an efficacy level of 30 per cent, lower than the earlier interim study results suggesting the efficacy was 50 per cent.
“At this point, MSD hasn’t offered any explanation (for the drop), so we should carefully monitor upcoming data,” Dr Leong said. He nonetheless welcomed the news of molnupiravir’s interim approval.
“Right now, the more the merrier when it comes to having diverse option for drug treatments... Given that some people are deemed to have an extremely high risk of dying (should they have Covid-19), having some form of medication, even if it’s just 30 per cent efficacy, may be all that is needed,” he added.
Of those who took molnupiravir in the study, 6.8 per had progressed to hospitalisation or death, compared to 9.7 per cent of participants who did not.
Molnupiravir should be administered within five days of the onset of symptoms for a duration of five days.
It may be used by individuals aged 18 years and above, who are at risk of progressing to severe Covid-19 or hospitalisation, and for people for whom alternative Covid-19 treatment options are not clinically appropriate, HSA said.
What are the risks around the drug?
In a sub-group analysis of participants who had the Sars-CoV-2 antibody at baseline, 3.7 per cent of those who took molnupiravir had progressed to hospitalisation or death, compared to 1.4 per cent who took the placebo.
HSA noted that this is “clinically relevant” in Singapore, given that most people have been fully vaccinated and would therefore have the antibodies.
The finding suggested that patients with the antibodies may have higher risk of hospitalisation or death when they took the pill, but experts warned that it may not necessarily be an accurate assumption.
A sub-group analysis is when participants are grouped into subsets based on shared characteristics — in this case, the presence of antibodies.
The study was not focused on finding out how those with antibodies react to molnupiravir, and Dr Asok Kurup from Mount Elizabeth Hospital said that more data is needed before coming to a conclusion.
He noted that patients with the antibodies could have had the vaccination, or from having been naturally infected with Covid-19, among other reasons.
“As we begin to understand the impact transposed to the vaccinated population, I think we have to be judicious in how we use it,” Dr Asok said.
Dr Leong said: “It’s good that HSA spotted it, as it shows the authority is thorough in studying the data. We should not immediately discard this drug, but observe it further.
“At the end of the day, doctors have to weigh the advantages and disadvantages of using the drug.”
Side effects of molnupiravir found in clinical studies included diarrhoea, nausea, and dizziness, which were generally mild in intensity, HSA said.
Molnupiravir is not recommended for use in pregnant women, lactating mothers and those below 18 years old.
HSA also said that people should use contraception if they have sex while being treated with molnupiravir and for four days after their last dose, because findings from animal studies showed that the drug may affect foetal growth, bone and cartilage development, and the DNA of the baby.
How does molnupiravir compare to other authorised Covid-19 drugs?
Aside from oral antiviral medicines molnupiravir and paxlovid, Singapore has also approved other medicines for treating Covid-19 such as Evusheld, which is administered by injection, and remdesivir, which is administered by intravenous drip.
Associate Professor Hsu Li Yang from the National University of Singapore’s Saw Swee Hock School of Public Health noted the impact of the Omicron variant of Covid-19 on some other treatments.
“Molnupiravir’s efficacy is comparable to existing antivirals against Covid-19, including the more expensive monoclonal antibody cocktails, several of which have lost their efficacy against the Omicron variant,” he told TODAY.
In a document on treatment guidelines for Covid-19 released on March 23, the National Centre for Infectious Diseases said that casirivimab or imdevimab by Roche-Regenero, a type of monoclonal antibody treatment given intravenously, should not be used on patients with the Omicron variant.
Dr Leong noted that the oral antiviral medicines are cheaper, which makes them more accessible.
Dr Asok said that oral drugs can be administered via clinics, which lightens the load on hospitals.
Comparing the two oral antiviral medicines, paxlovid has a higher efficacy rate as clinical studies found it to reduce the risk of Covid-19-related hospitalisation or death by 88.9 per cent when treatment was given within three days of the onset of symptoms, and by 87.8 per cent when given within five days of the onset of symptoms.
However, paxlovid contains ritonavir, which interacts with some commonly used drugs and cannot be taken by some individuals, such as those with severe kidney failure.
Assoc Prof Hsu said that molnupiravir should not be given to pregnant and breastfeeding women, which does not apply to paxlovid. That means one of the two drugs can be used for patients for whom the other drug is not medically suitable.
Dr Asok said: “As we go towards an endemic situation, we’ll have to live with Covid-19 and that means we will see vulnerable individuals catching it, so it is important we have alternative medications.” — TODAY
