Merck’s Antiviral COVID-19 Pill Approved in Singapore

An experimental COVID-19 treatment pill called molnupiravir being developed by Merck & Co. Inc. and Ridgeback Biotherapeutics LP, is seen in this undated photo obtained by Reuters on May 17, 2021. (Merck & Co. Inc./Handout via Reuters)

Singapore has approved a second oral antiviral drug for treating COVID-19.

Molnupiravir, branded as Lagevrio, was granted interim authorization under the Pandemic Special Access Route (PSAR) by the Health Sciences Authority (HSA) on April 19.

The medicine was approved for treating mild to moderate COVID-19 patients aged 18 and above, who are at risk of developing severe illness or hospitalization, and in whom “alternative COVID-19 treatment options are not clinically appropriate,” according to the HSA.

Lagevrio should be taken within five days of experiencing symptoms for a duration of five days.

“It will be prescribed and prioritized to those at higher risk of severe disease, as directed by the Ministry of Health,” said the authority.

Earlier in January, Singapore approved Pfizer’s Paxlovid tablet under the PSAR for treating adult COVID-19 patients to reduce the risk of hospitalization and death.

Introduced in 2020, the PSAR helps expedite early access to vaccines, medicines, and medical devices during the pandemic.

With the interim authorization, Merck, also known as MSD outside the United States and Canada, is required to submit updated data from ongoing clinical studies for continual assessment of the benefits and risks of Lagevrio.

The interim authorization may also be terminated at any time if the benefits no longer outweigh the risks.

The Merck logo is seen at a gate to the Merck & Co. campus in Rahway, N.J., on July 12, 2018. (Brendan McDermid/Reuters)

Efficacy

HSA’s review of the drug was based on clinical trial results which showed that it had a 30 percent relative reduction in the risk of hospitalization and death.

The efficacy analysis was based on 709 participants who received Lagevrio and 699 participants who received a placebo. All participants were aged between 18 and 90 with several risk factors of developing severe disease.

Common risk factors include obesity, older age, diabetes, and heart disease, according to Merck.

The Lagevrio group had a 6.8 percent rate of hospitalization or death. The rate for the placebo group was 9.7 percent.

“As of the latest data cut-off date, there were 48 hospitalizations with two subsequent deaths in the Lagevrio arm, and 68 hospitalizations with 12 subsequent deaths in the placebo arm,” said the HSA in its press release.

The 30 percent efficacy rate is lower than the earlier reported 50 percent according to the interim results released last October.

Nicholas Kartsonis, senior vice president of clinical research for infectious diseases and vaccines at Merck, said that there was no clear explanation for the difference in results, during a U.S. Food and Drug Administration (FDA) advisory committee on Nov. 30, 2021 (pdf).

The committee narrowly voted to recommend the FDA grant emergency use authorization (EUA) for the drug on the same day, agreeing with the idea that the drug’s benefits outweigh its potential risks.

Despite the lower efficacy of Lagevrio compared to other authorized 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,” said Singapore’s HSA.

“Clinicians must carefully assess that the potential benefits outweigh the risks in the patient before initiating Lagevrio treatment.”

The earlier-approved Pfizer’s Paxlovid had a relative hospitalization and death risk reduction of 88.9 percent compared to the placebo group when participating patients took it within three days of experiencing symptoms, according to clinical study results. The efficacy dropped to 87.8 percent when the treatment was given within five days of experiencing symptoms.

Although having a higher efficacy rate, Paxlovid may interact with several medications, including those for irregular heart rate, migraine, and cholesterol, which could cause “serious adverse events,” said the HSA.

Risks

A higher proportion of 3.7 percent of participants in the group who took Lagevrio had progressed to hospitalization or death, compared to 1.4 percent in the placebo arm, in a subgroup analysis of participants who had SARS-CoV-2 antibodies at baseline.

The subgroup analysis would be a “clinically relevant consideration in Singapore” given that most people have been fully vaccinated and would have the antibodies, according to the HSA.

Commenting on the results, Dr. Asok Kurup from Mount Elizabeth Hospital told local outlet TODAY that patients with antibodies may have received vaccination, or they may have been infected before, among other possibilities.

“As we begin to understand the impact transposed to the vaccinated population, I think we have to be judicious in how we use it,” said Kurup.

The common side effects of Lagevrio identified in clinical trials include diarrhea, nausea, and dizziness, which the HSA said “were generally mild in intensity.”

Lagevrio is not recommended for pregnant women, lactating mothers, and people below 18 years old.

As findings from animal-based studies suggest that Lagevrio may affect fetal growth, bone and cartilage development, and DNA, women with childbearing potential and men with partners of childbearing potential should use reliable contraceptive methods during treatment.

After the last dose of Lagevrio, women should continue to use contraceptive methods for another four days, while men need to use contraceptive methods for at least three months, according to the HSA.

Mimi Nguyen Ly contributed to this report.