Singapore approves molnupiravir, second oral antiviral drug allowed for treatment of COVID-19

SINGAPORE: The antiviral drug molnupravir will be the second oral medicine approved in Singapore for the treatment of adult COVID-19 patients, said the Health Sciences Authority (HSA) on Tuesday (Apr 19). 

Interim authorisation was granted under the Pandemic Special Access Route (PSAR) for MSD's Lagevrio on Tuesday, said HSA, in consultation with its Medicines Advisory Committee. 

Molnupiravir, marketed as Lagevrio, is the second oral antiviral medicine authorised for treating mild to moderate COVID-19 in patients aged 18 years and above, those who are at risk of progressing to severe COVID-19 or hospitalisation or both, and in whom "alternative COVID-19 treatment options are not clinically appropriate". 

In February, Singapore approved the use of Pfizer's Paxlovid pill for the treatment of COVID-19 in adult patients who are at risk of severe disease. 

Lagevrio should be taken within five days of the onset of symptoms for a duration of five days, said HSA. It will be prescribed to and prioritised for those at higher risk of severe illness, as directed by the Ministry of Health (MOH). 

Lagevrio has been found to reduce the risk of severe COVID-19 by 30 per cent, and the risk of hospitalisation or death by 6.8 per cent, according to HSA's review based on the clinical data from a phase II/III study. The study investigated the use of the drug in reducing the risk of hospitalisation or deaths in patients with mild to moderate COVID-19. 

THE STUDY

About 1,400 people aged 18 to 90 participated in the randomised, placebo-controlled study, said HSA. All participants had one or more risk factors for progression to severe COVID-19. 

A total of 709 participants were given Lagevrio and the other 699 people received placebos, said HSA. 

Results showed an efficacy of 30 per cent relative risk reduction with Lagevrio compared to those given placebos. For those given Lagebrio, the rates of progression to hospitalisation or death were 6.8 per cent, compared to 9.7 per cent in those given placebos. 

As of the latest data cut off date, there were 48 hospitalisations with two subsequent deaths in the Lagevrio group. Sixty-eight hospitalisations with 12 subsequent deaths were recorded in the placebo group, said HSA. 

In a subgroup analysis of participants who had the SARS-CoV-2 antibody at baseline, there was a higher proportion of subjects in the Lagevrio group who had progressed to hospitalisation or death (3.7 per cent) compared to those given placebos (1.4 per cent). 

 "This is a clinically relevant consideration in Singapore given that most of our population has been fully vaccinated and most would have SARS-CoV-2 antibodies," said HSA. 

While the study results indicated that the drug has lower efficacy compared to other authorised COVID-19 treatments, the authority said Lagevrio may have a place in therapy for patients who are at risk of progressing to severe COVID-19, and in whom current available treatment options are "clinically inappropriate". 

"Clinicians must carefully assess that the potential benefits outweigh the risks in the patient before initiating Lagevrio treatment," said HSA. 

GROUPS THAT SHOULD NOT TAKE LAGEVRIO

Lagevrio is not recommended for use in pregnant women, lactating mothers and those below 18 years old, said HSA. 

"Women of childbearing potential should use a reliable method of contraception for the duration of treatment and for four days after the last dose of Lagevrio." 

The authority also advised men with partners of childbearing potential to use reliable contraceptive methods during treatment for at least three months after the last dose. 

The recommendations were based on findings from animal studies which showed that Lagevrio may affect foetal growth, bone and cartilage development, and DNA. 

Common adverse events of Lagevrio reported in clinical studies include diarrhoea, nausea and dizziness which were generally mild in intensity, said HSA. 

MSD, the company which developed the drug, is required to submit updated data from ongoing clinical studies to ensure the continued safety and efficacy of Lagevrio for HSA's continual benefit-risk assessment. 

"HSA will actively review post-authorisation safety monitoring data and the data submitted by MSD to ensure that the benefits of Lagevrio continue to outweigh the known risks," it said. 

The authority added as PSAR is an interim authorisation, MSD is required to submit the complete dataset based on prevailing international standards to obtain a full registration.

The PSAR interim authorisation may also be terminated at any time, said HSA, for example, if new data suggest that the benefits no longer outweigh the risk.

MORE CLINICS ALLOWED TO PRESCRIBE PAXLOVID 

In a separate press release on Tuesday, MOH said more clinics will be able to prescribe Pfizer's Paxlovid pill to COVID-19 patients who are at risk of severe disease. 

Sixteen more Public Health Preparedness Clinics will be coming on board a pilot programme to prescribe the pill for COVID-19 patients at risk of severe disease and who are accessed by their doctors to be clinically eligible to receive the treatment, said MOH. 

This is part of the Health Ministry's efforts to treat COVID-19 in community settings, it said. 

"This is in addition to all polyclinics and the 20 PHPCs that are currently participating in the pilot programme," MOH added.

List of clinics that can prescribe Paxlovid to eligible COVID-19 patients:

List of clinics that will progressively be able to prescribe Paxlovid to eligible patients:

"For now, MOH will fully cover the drug cost of Paxlovid use in primary care settings, regardless of the patient’s vaccination status, as it can reduce the likelihood of high-risk patients developing severe COVID-19 and requiring hospital admission," said the Health Ministry, adding that the charging policy for Paxlovid will be reviewed in "due course". 

Early treatment with Paxlovid may be considered for COVID-19 patients who meet certain criteria, including COVID-positive patients aged 18 and older, present within five days of illness and are at risk of developing severe disease, such as those who have active cancer, serious heart conditions, or are on ongoing immunosuppressive condition or treatment. 

"As Paxlovid has potential interactions with many other commonly used medications, the decision to take Paxlovid has to be carefully considered by the primary care doctor, and after discussion with the patients on the benefits and risks," said MOH. 

The Health Ministry will also continue to monitor the usage of Paxlovid and review patient outcomes. It will also monitor the demand closely and maintain a "healthy stock" of the drug.