MSD’s COVID-19 oral antiviral LAGEVRIO® receives interim authorization in Singapore

April 20, 2022 1:14 pm Asia/Singapore

Demonstrated efficacy from the MOVe-OUT phase 3 trial in non-hospitalized at-risk adults with COVID-19 indicate that LAGEVRIO® (molnupiravir), initiated within 5 days from the onset of symptoms, reduced the risk of hospitalization or death from the time of randomization through Day 29.

SINGAPORE, April 19, 2022 – MSD (NYSE: MRK), known as Merck & Co., Inc., Kenilworth, NJ, USA in the United States and Canada today announced that LAGEVRIO® (molnupiravir), an oral antiviral treatment for adults with mild to moderate COVID-19 has received interim authorization by the Health Sciences Authority (HSA) under the Pandemic Special Access Route (PSAR).   

In line with the authorization, LAGEVRIO® will be made available as an oral antiviral for the treatment of mild to moderate COVID-19 patients aged 18 years and above who are at high risk for progressing to severe COVID-19 and/or hospitalization, and in whom alternative COVID-19 treatment options are not clinically appropriate.

LAGEVRIO® works by inserting itself into the viral RNA of SARS-CoV2 leading to inhibition of viral replication.

The authorization is based on the positive results from a planned interim analysis of the Phase 3 MOVe-OUT global trial, as well as a recent study update, which evaluated LAGEVRIO® compared to placebo in adult patients who were unvaccinated against SARS-CoV-2, had a confirmed SARS-CoV-2 infection, experienced symptom onset within five days of study randomization, and had at least one risk factor associated with poor disease outcomes including age >60 years, obesity, diabetes, or cardiovascular disease.¹

The study found that early treatment with molnupiravir helped reduce the risk of hospitalizations or death from the time of randomization through Day 29.

LAGEVRIO® is generally well-tolerated, with no serious safety concerns identified. It is the only oral COVID-19 treatment with no known contraindications or expected drug interactions, enabling appropriate use in patients with comorbidities and concomitant medications. It also requires no dosage adjustment for patients with impaired kidney or liver function.

The World Health Organization (WHO) recently added a new recommendation on LAGEVRIO® for COVID-19 patients with non-severe illness. Locally, LAGEVRIO® is included in National Centre for Infectious Disease (NCID) treatment guidelines for COVID-19.

“Based on available efficacy data and the demonstration of a reduction in the risk of death by 89% – molnupiravir, an oral antiviral agent, is an important tool to Singapore’s pandemic response. Combined with vaccines, oral antiviral treatments may help mitigate the risk of disease progression or death in select vulnerable groups who continue to bear the brunt of this pandemic. Oral antivirals can allow healthcare professionals to help high-risk patients with mild to moderate symptoms in community settings as soon as they test positive to help limit disease progression. High-risk patients can remain at home and still be actively treated,” said Dr Asok Kurup, Infectious Disease Specialist at Infectious Diseases Care, Mt Elizabeth Medical Centre.

“LAGEVRIO®, a single oral medicine with demonstrated efficacy and convenient administration, has a role in addressing high-risk patient needs. Molnupiravir has shown to be effective against a range of variants, and new findings demonstrating in vitro activity against the Omicron variant provide additional confidence in the potential of molnupiravir as an important treatment option for those who are at high risk for progression to severe disease,” said Dr. Aileen Dualan, Asia Pacific Head of Medical Affairs, MSD.

In October 2021, MSD announced that the Singapore Government entered into an advanced supply and purchase agreement with MSD to secure courses of LAGEVRIO® for the population once authorized or approved.

“LAGEVRIO® marks another milestone in MSD’s long legacy of industry-leading research in the development of therapeutics and vaccines against infectious diseases, which is consistent with our unwavering commitment to saving and improving lives for over 130 years. We believe that a variety of treatments and vaccines are needed to overcome the pandemic. We are committed towards working closely with the Singapore government to make LAGEVRIO® as widely accessible to eligible Singapore patients as quickly as possible,” said Pang Lai Li, Managing Director of Singapore and Malaysia, MSD.

As of March 28, 2022, MSD has entered into advanced supply and purchase agreements for molnupiravir with governments from over 35 markets worldwide, including The United States, Australia, Canada, South Korea, Japan, Thailand, Singapore, Brunei, and United Kingdom pending regulatory authorizations, and is currently in discussions with other governments. As of March 28, 2022, Molnupiravir has received regulatory authorization or approval in over 10 markets.

LAGEVRIO® Selected Safety Information (SSI)¹

INDICATIONS

LAGEVRIO (molnupiravir) is indicated for the treatment of mild to moderate COVID-19 in adults who are at risk for progressing to severe COVID-19 and/or hospitalization.

DOSAGE AND METHOD OF USE

Recommended dose of LAGEVRIO in adult patients is 800 mg (four 200 mg capsules) taken orally every 12 hours for 5 days, with or without food.

LAGEVRIO should be administered as soon as possible after a diagnosis of COVID-19 has been made and within 5 days of symptom onset in adults who are at risk for progression to severe COVID-19.

Safety and efficacy of LAGEVRIO have not been established in pediatric patients less than 18 years of age.

No dose adjustment of LAGEVRIO is recommended for geriatric patients, patients with renal impairment and hepatic impairment.

LAGEVRIO is not recommended to be taken during pregnancy.

CONTRAINDICATIONS

None.

WARNING AND PRECAUTIONS

None.

ADVERSE EVENTS

Clinical Trials Experience

Interim analysis of a Phase 3 double-blind trial (MOVe-OUT) was carried out to evaluate safety of LAGEVRIO in which 765 non-hospitalized subjects with COVID-19 were randomized and treated with LAGEVRIO (N=386) or placebo (N=379) for up to 5 days and followed through Day 29. Adverse events were those reported while subjects were on study intervention or within 14 days of study intervention completion/discontinuation.

Occurrence of adverse events in 1% of subjects receiving molnupiravir and 3% of subjects receiving placebo resulted in discontinuation of study intervention. Serious adverse events occurred in 7% of subjects receiving molnupiravir and 14% receiving placebo; none was considered drug- related by the investigator and most were COVID-19 related. Adverse events leading to death occurred in none of the subjects receiving molnupiravir and 2.3% of subjects receiving placebo.

Most common adverse reactions in molnupiravir treatment group in MOVe-OUT are diarrhea, nausea, dizziness and headache.

Full prescribing information is available upon request.

About Molnupiravir

Molnupiravir (MK-4482) is an investigational, orally administered nucleoside analog that inhibits the replication of SARS-CoV-2, the causative agent of COVID-19. MSD and Ridgeback’s “orange COVID-19 pill” is a Swedish Orange opaque capsule with the MSD corporate logo and “82” printed in white ink, available in certain markets outside of the U.S. as LAGEVRIO®.

Results from the Phase 3 MOVe-OUT study demonstrated the efficacy benefit of molnupiravir treatment was generally consistent across patients infected with SARS-CoV-2 variants of concern, Delta, Gamma and Mu. Preliminary preclinical data has shown that molnupiravir has antiviral activity against the newly identified variant, Omicron (B1.1.529). Molnupiravir has yet to be evaluated against Omicron in clinical studies.

Molnupiravir was invented at Emory University. Drug Innovation Ventures at Emory (DRIVE), LLC, which was formed by Emory to develop early-stage drug candidates for viral diseases of global concern, advanced molnupiravir through IND submission. Emory/DRIVE received some research funding from the U.S. Department of Defense and the U.S. National Institutes of Health. Molnupiravir is being developed by MSD in collaboration with Ridgeback Biotherapeutics. Ridgeback received an upfront payment from MSD and also is eligible to receive contingent payments dependent upon the achievement of certain developmental and regulatory approval milestones. Any profits from the collaboration will be split between the partners equally. Since licensed by Ridgeback, all funds used for the development of molnupiravir have been provided by MSD and Ridgeback.

Molnupiravir was evaluated in MOVe-OUT, a global Phase 3, randomized, placebo-controlled, double-blind, multi-site study of non-hospitalized adult patients with symptomatic, laboratory-confirmed mild to moderate COVID-19 and at least one risk factor associated with poor disease outcomes. The Phase 3 portion of the MOVe-OUT trial was conducted globally in more than 170 sites in locations including Argentina, Brazil, Canada, Chile, Colombia, Egypt, France, Germany, Guatemala, Israel, Italy, Mexico, Philippines, Poland, Russia, South Africa, Spain, Sweden, Taiwan, Ukraine, the United Kingdom and the United States. For further information about the MOVe-OUT trial, please visit clinicaltrials.gov. Molnupiravir is also being evaluated for post-exposure prophylaxis in MOVe-AHEAD, a global, multicenter, randomized, double-blind, placebo-controlled Phase 3 study evaluating the efficacy and safety of molnupiravir in preventing the spread of COVID-19 within households. For more information, please visit http://msdcovidresearch.com.

B-roll and photography relating to molnupiravir and the arrival of molnupiravir shipment are available here

About the MOVe-OUT Study

The MOVe-OUT trial (MK-4482-002) (NCT04575597) was a global Phase 3, randomized, placebo-controlled, double-blind, multi-site study of non-hospitalized adult patients with laboratory-confirmed mild-to-moderate COVID-19. Patients enrolled in the study were unvaccinated against SARS-CoV-2, had at least one risk factor associated with poor disease outcomes, and symptom onset within five days prior to randomization. The primary efficacy objective of MOVe-OUT is to evaluate the efficacy of molnupiravir 800 mg twice daily for five days compared to placebo as assessed by the percentage of participants who are hospitalized and/or die from the time of randomization through Day 29.

The Phase 3 portion of the MOVe-OUT trial was conducted globally in more than 170 sites, in locations including Argentina, Brazil, Canada, Chile, Colombia, Egypt, France, Germany, Guatemala, Israel, Italy, Mexico, Philippines, Poland, Russia, South Africa, Spain, Sweden, Taiwan, Ukraine, the United Kingdom and the United States. For further information about the MOVe-OUT trial, please visit clinicaltrials.gov.

The most common risk factors for poor disease outcome included obesity, older age (>60 years), diabetes mellitus and heart disease. Delta, Gamma and Mu variants accounted for the vast majority of the baseline viral variants that had been sequenced at the time of the interim analysis.

About Ridgeback Biotherapeutics

Headquartered in Miami, Florida, Ridgeback Biotherapeutics LP is a biotechnology company focused on emerging infectious diseases. Ridgeback markets Ebanga^TM for the treatment of Ebola and has a late-stage development pipeline which includes molnupiravir for the treatment of COVID-19. The team at Ridgeback is dedicated to developing life-saving and life-changing solutions for patients and diseases that need champions as well as providing global access to these medicines. In line with Ridgeback’s mission for equitable global access, all Ridgeback services and treatment for Ebola patients in Africa are delivered free of charge.

About MSD

At MSD, known as Merck & Co., Inc., Kenilworth, NJ, USA in the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.msd-singapore.com and connect with us on Twitter, LinkedIn and YouTube.

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