The Health Sciences Authority (HSA), in consultation with its Medicines Advisory Committee, has granted interim authorisation under the Pandemic Special Access Route (PSAR) for MSD’s LAGEVRIO (molnupiravir) on 19 April 2022. LAGEVRIO is the second oral antiviral medicine[1] authorised for the treatment of mild to moderate COVID-19 in individuals aged 18 years and above, who are at risk of progressing to severe COVID-19 and/or hospitalisation, and in whom alternative COVID-19 treatment options are not clinically appropriate. It should be administered within 5 days of symptom onset for a duration of 5 days. It will be prescribed and prioritised to those at higher risk of severe COVID illness, as directed by the Ministry of Health.
Efficacy and use
2 HSA’s review was based on the clinical data from a phase II/III study investigating the use of LAGEVRIO in reducing the risk of hospitalisation or deaths in patients with mild-to-moderate COVID-19. The randomised, placebo-controlled study recruited about 1,400 participants aged 18 to 90 years who had one or more risk factors for progression to severe COVID-19. The efficacy analysis comprised 709 participants who received LAGEVRIO and 699 who received placebo.
3 The results showed an efficacy of 30% relative risk reduction with LAGEVRIO compared to placebo. The rates of progression to hospitalisation or death were 6.8% in the LAGEVRIO arm and 9.7% in the placebo arm. As of the latest data cut-off date, there were 48 hospitalisations with 2 subsequent deaths in the LAGEVRIO arm, and 68 hospitalisations with 12 subsequent deaths in the placebo arm.
4 In a subgroup analysis of participants who had SARS-CoV-2 antibody at baseline, there was a higher proportion of subjects in the LAGEVRIO arm (3.7%) who had progressed to hospitalisation or death compared to the placebo arm (1.4%). 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.
5 While the study results indicated that LAGEVRIO has lower efficacy compared to other authorised COVID-19 treatments, it 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.
Precautions on use
6 LAGEVRIO is not recommended for use in pregnant women, lactating mothers, and those below 18 years old. Women of childbearing potential should use a reliable method of contraception for the duration of treatment and for 4 days after the last dose of LAGEVRIO. Men with partners of childbearing potential should use reliable contraceptive methods during treatment and for at least 3 months after the last dose of LAGEVRIO. These recommendations are based on findings from animal studies which showed that LAGEVRIO may affect foetal growth, bone and cartilage development, and DNA.
7 The common adverse events of LAGEVRIO reported in the clinical studies include diarrhoea, nausea and dizziness which were generally mild in intensity.
Active monitoring and continuous review of data
8 MSD 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.
9 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. As PSAR is an interim authorisation, the company is required to submit the complete dataset based on prevailing international standards[2] to obtain a full registration. The PSAR interim authorisation may also be terminated at any time; for example, if new data suggests that the benefits no longer outweigh the risks.
[1] Paxlovid™ was the first oral antiviral medicine authorised by HSA on 31 January 2022 for the treatment of mild to moderate COVID-19 in adult patients who are at high risk of progression to severe disease, to reduce the risk of hospitalisation and death.
[2] HSA’s current requirements are based on the scientific standards set out by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH).
HEALTH SCIENCES AUTHORITY
SINGAPORE
19 APRIL 2022