The fight against COVID-19 has not been an easy one. The entire world has been fighting this battle for almost 3 years now, and though we have made significant progress there is still so much more to be done. In tremendous efforts, scientists with the backing of pharmaceutical company power and technology have found new ways to fight this disease. We have even reached the state in which the virus is mutating and with that, some drugs that were effective against certain mutations are becoming obsolete in the treatment of newer variations. In the biggest leap yet, two companies have put forth by mouth treatments for COVID-19. These treatments may seem to be just more COVID-19 medications authorized by different governments, but they provide great attributes that previously authorized medication did not. Because these medications come in a tablet dosage form, they can be taken at home. They do not require a visit to an ambulatory or hospital site for treatment. Patients can walk into their local pharmacies, a place they are more than likely familiar with, and receive this treatment.
Molnupiravir is a small-molecule ribonuclease prodrug of N- hydroxycytidine. This drug has activity against the virus that causes COVID-19 and a strong barrier to the development of resistance. Mechanistically, the drug works by causing the viral polymerase to insert guanosine or adenosine during viral replication. This causes several errors throughout the viral genome causing the virus to eventually become non-infectious and leave it unable to properly replicate. In its phase 3 clinical trials, Molnupiravir met its pre-specified superiority criterion during its interim analysis on day 29, the final day of observation of patients on the medication. In the intention-to-treat population, participants receiving molnupiravir had a lower risk of hospitalization or death through day 29: 6.8% (48 of 709 participants). Regarding safety, the percentage of patients experiencing at least one adverse event was similar in the molnupiravir vs. placebo groups. Deaths that resulted from adverse events, which was deemed not to be related to the trail regimen, were reported less often in the molnupiravir group than placebo.
Many patients who suffer from COVID-19 do recover from acute infections. It is those patients whom the disease progresses that have an impact on health-systems, causing an increased risk of hospital overburden that are of concern. An interesting note of this trial is that only patients who were not vaccinated against COVID-19 were eligible to participate. This choice was reported by investigators as a need to focus on those more likely to need antiviral treatment. This is an especially important idea to consider when thinking about countries that do not have easy access to vaccines. Vaccines need to be transported and delivered under stringent temperature conditions. These conditions can be difficult to maintain when the vaccines need to be sent especially long distances. Though vaccines are the best way to remain safe from COVID-19, having an easily taken and easily transportable treatment for the virus is the next best thing.
References:
1. Jayk Bernal A, Gomes da Silva MM, Musungaie DB, et al. Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients [published online ahead of print, 2021 Dec 16]. N Engl J Med. 2021;NEJMoa2116044. doi:10.1056/NEJMoa2116044
2. Merck and Ridgeback's molnupiravir receives U.S. FDA emergency use authorization for the treatment of high-risk adults with mild to moderate COVID-19. Merck.com. https://www.merck.com/news/merck-and-ridgebacks-molnupiravir-receives-u-s-fda-emergency-use-authorization-for-the-treatment-of-high-risk-adults-with-mild-to-moderate-covid-19/#:~:text=Molnupiravir%20has%20not%20been%20approved,severe%20COVID%2D19%2C%20including%20hospitalization. Published December 23, 2021. Accessed February 1, 2022.
Molnupiravir
The fight against COVID-19 has not been an easy one. The entire world has been fighting this battle for almost 3 years now, and though we have made significant progress there is still so much more to be done. In tremendous efforts, scientists with the backing of pharmaceutical company power and technology have found new ways to fight this disease. We have even reached the state in which the virus is mutating and with that, some drugs that were effective against certain mutations are becoming obsolete in the treatment of newer variations. In the biggest leap yet, two companies have put forth by mouth treatments for COVID-19. These treatments may seem to be just more COVID-19 medications authorized by different governments, but they provide great attributes that previously authorized medication did not. Because these medications come in a tablet dosage form, they can be taken at home. They do not require a visit to an ambulatory or hospital site for treatment. Patients can walk into their local pharmacies, a place they are more than likely familiar with, and receive this treatment.
Molnupiravir is a small-molecule ribonuclease prodrug of N- hydroxycytidine. This drug has activity against the virus that causes COVID-19 and a strong barrier to the development of resistance. Mechanistically, the drug works by causing the viral polymerase to insert guanosine or adenosine during viral replication. This causes several errors throughout the viral genome causing the virus to eventually become non-infectious and leave it unable to properly replicate. In its phase 3 clinical trials, Molnupiravir met its pre-specified superiority criterion during its interim analysis on day 29, the final day of observation of patients on the medication. In the intention-to-treat population, participants receiving molnupiravir had a lower risk of hospitalization or death through day 29: 6.8% (48 of 709 participants). Regarding safety, the percentage of patients experiencing at least one adverse event was similar in the molnupiravir vs. placebo groups. Deaths that resulted from adverse events, which was deemed not to be related to the trail regimen, were reported less often in the molnupiravir group than placebo.
Many patients who suffer from COVID-19 do recover from acute infections. It is those patients whom the disease progresses that have an impact on health-systems, causing an increased risk of hospital overburden that are of concern. An interesting note of this trial is that only patients who were not vaccinated against COVID-19 were eligible to participate. This choice was reported by investigators as a need to focus on those more likely to need antiviral treatment. This is an especially important idea to consider when thinking about countries that do not have easy access to vaccines. Vaccines need to be transported and delivered under stringent temperature conditions. These conditions can be difficult to maintain when the vaccines need to be sent especially long distances. Though vaccines are the best way to remain safe from COVID-19, having an easily taken and easily transportable treatment for the virus is the next best thing.
References:
1. Jayk Bernal A, Gomes da Silva MM, Musungaie DB, et al. Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients [published online ahead of print, 2021 Dec 16]. N Engl J Med. 2021;NEJMoa2116044. doi:10.1056/NEJMoa2116044
2. Merck and Ridgeback's molnupiravir receives U.S. FDA emergency use authorization for the treatment of high-risk adults with mild to moderate COVID-19. Merck.com. https://www.merck.com/news/merck-and-ridgebacks-molnupiravir-receives-u-s-fda-emergency-use-authorization-for-the-treatment-of-high-risk-adults-with-mild-to-moderate-covid-19/#:~:text=Molnupiravir%20has%20not%20been%20approved,severe%20COVID%2D19%2C%20including%20hospitalization. Published December 23, 2021. Accessed February 1, 2022.