Phase III MOVe-NOW Trial to Evaluate New Lagevrio Formulation Targeting High-Risk COVID-19 Patients

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Merck and Ridgeback Biotherapeutics have announced the initiation of the Phase III MOVe-NOW trial (NCT06667700), which will assess a new formulation of Lagevrio (molnupiravir) for the treatment of non-hospitalized adult patients with COVID-19 who have an elevated risk of disease progression and who cannot use other antiviral treatments.^1,2

Lagevrio, an oral antiviral medication, was previously granted FDA Emergency Use Authorization (EUA) to treat adults with a current diagnosis of mild-to-moderate COVID-19 with a high risk of progressing to severe COVID-19, including hospitalization or death, and for whom alternative approved therapies are not accessible or clinically appropriate. Notably, Lagevrio is not approved for any use, including COVID-19 treatment, but is authorized for emergency use under the FDA’s EUA.

The MOVe-NOW trial will investigate a new formulation of the drug, which includes two smaller 400 mg tablets per dose for a total of four daily tablets instead of its current formulation of four 200 mg capsules per dose for a total of eight daily capsules.

“COVID-19 remains a leading cause of hospitalization and death around the world, and further studying Lagevrio may provide important insights into how it may be used to help prevent severe outcomes in the current COVID-19 environment,” Paula Annunziato, MD, senior vice president, infectious diseases and vaccines, Global Clinical Development, Merck Research Laboratories, said in a press release.¹

Trial Design

The multicenter, randomized, double-blind, placebo-controlled MOVe-NOW trial will compare the efficacy and safety of oral Lagevrio vs. placebo in non-hospitalized adults with COVID-19 at high risk for disease progression. Investigators anticipate enrolling approximately 3,082 patients, who will be randomly assigned to receive Lagevrio at a dose of 800 mg or placebo orally every 12 hours for five days.

Enrollment criteria includes being at least 18 years of age and having received a positive SARS-CoV-2 test, with signs or symptoms attributed to COVID-19 for four days or less. Investigators will only enroll adults who are ineligible for treatment with nirmatrelvir/ritonavir because of drug-drug interactions, allergy, prior experience of adverse events (AEs), or inaccessibility.

The trial will be conducted in 25 markets worldwide, including the United States, Japan, Korea, Taiwan, the United Kingdom, France, Italy, Spain, Ukraine, Poland, Mexico, and Colombia. Additionally, investigators have the option of treating some patients with concomitant remdesivir, if available and clinically appropriate per local practice, in addition to Lagevrio or placebo.

Trial Endpoints

The trial’s primary efficacy and safety endpoints include percentage of patients who are hospitalized or died for any reason or had a COVID-19-related, medically-attended visit through day 29; percentage of those experiencing AEs; and percentage of those who discontinued Lagevrio because of AEs. Key secondary endpoints include sustained alleviation of specific patient-reported COVID-19 signs and symptoms without relapse through day 29; analysis of SARS-CoV-2 viral load through day 29; time to sustained resolution of the signs and symptoms of COVID-19 without relapse; and percentage of patients with clinically relevant medical interventions associated with a COVID-19-related medically attended visit or hospitalization through day 29, or who experienced hospitalization or death due to any cause.

The study will include an extended follow up after the end of treatment of approximately five-and-a-half months to analyze the endpoints associated with post-acute sequelae of COVID-19 (PASC), also known as long COVID. Investigators will evaluate the development of PASC on day 29 and throughout the extended follow-up period based on self-reported COVID-19 signs and symptoms.

Previously published results from the Phase III MOVe-OUT trial (NCT04575597) published in the Annals of Internal Medicine show the efficacy of Lagevrio treating non-hospitalized adults with mild to moderate COVID-19 with high risk of progressing to severe disease.^3,4

Pre-specified exploratory endpoints demonstrated that 7.2% of patients administered Lagevrio in the modified intent-to-treat population had an acute care visit or a COVID-19-related acute care visit compared to 10.6% of those given a placebo in the modified intent-to-treat population through day 29, translating to a relative risk reduction (RRR) of 32.1%. Further, 6.6% of patients administered Lagevrio reported a COVID-19-related acute care visit compared with 10% of patients given placebo, translating to an RRR of 33.8%.

Additionally, fewer patients administered Lagevrio in the modified intent-to-treat population required respiratory interventions, which includes conventional oxygen therapy, high-flow heated and humidified device, invasive mechanical ventilation, or noninvasive mechanical ventilation compared to patients given a placebo, translating to an RRR of 34.3% for all respiratory interventions.

To date, Lagevrio has been administered to more than 8.3 million patients worldwide.¹

“We continue to believe Lagevrio may be an important option for people with risk factors like older age, multiple comorbidities, and immunocompromising conditions, who are more likely to advance to severe COVID-19, and for whom other antiviral treatments may not be appropriate because of the potential for drug-drug interactions,” Annunziato said.¹

References

1. Merck and Ridgeback Biotherapeutics Announce Initiation of Phase 3 Study (MOVe-NOW) Evaluating LAGEVRIO™ (molnupiravir) for the Treatment of COVID-19 in High-Risk Adults. News release. Merck. December 5, 2024. Accessed December 6, 2024. https://www.merck.com/news/merck-and-ridgeback-biotherapeutics-announce-initiation-of-phase-3-study-move-now-evaluating-lagevrio-molnupiravir-for-the-treatment-of-covid-19-in-high-risk-adults/

2. A Clinical Study of Molnupiravir to Prevent Severe Illness From Coronavirus Disease 2019 (COVID-19) in People Who Are High Risk (MK-4482-023) (MOVe-NOW). ClinicalTrials.gov. Updated November 21, 2024. Accessed December 6, 2024. https://clinicaltrials.gov/study/NCT06667700?term=molnupiravir&rank=6

3. Merck and Ridgeback announce new data for investigational Lagervrio (molnupiravir) from phase 3 MOVe-OUT study. Merck. News release. June 7, 2022. Accessed December 6, 2024. https://www.merck.com/news/merck-and-ridgeback-announce-new-data-for-investigational-lagevrio-molnupiravir-from-phase-3-move-out-study/

4. Efficacy and Safety of Molnupiravir (MK-4482) in Non-Hospitalized Adult Participants With COVID-19 (MK-4482-002). ClinicalTrials.gov. Updated June 28, 2023. Accessed December 6, 2024. https://clinicaltrials.gov/study/NCT04575597