La píldora de Merck contra el COVID-19 mostró efectividad contra Ómicron / Merck and Ridgeback’s Molnupiravir, an Investigational Oral Antiviral COVID-19 Medicine, Demonstrated Activity Against Omicron Variant in In Vitro Studies

Así lo indicaron seis estudios de laboratorio independientes realizados con el antiviral molnupiravir en EE.UU. y en cinco países europeos

La píldora contra el COVID-19 de las compañías biofarmacéuticas Merck & Co. y Ridgeback Biotherapeutics, de Estados Unidos, conocidas como MSD en América Latina, mostró que actúa contra la variante Ómicron del SARS-CoV-2 en seis estudios de laboratorio.

Esto aumenta la confianza en la capacidad de la nueva terapia para combatir la mutación dominante en casi todo el mundo, que es altamente contagiosa.

Estudios independientes realizados en EE.UU. y cinco países europeos estudiaron el impacto del molnupiravir de MSD y otros antivirales contra las variantes de interés, incluida Ómicron, dijeron este viernes la compañía Merck y su socio RidgebackBiotherapeutics LP en un comunicado.

El fármaco fue autorizado por los organismos reguladores de EE.UU. y el Reino Unido para tratar a los pacientes de COVID-19 con alto riesgo de enfermedad grave, después de que demostrara una eficacia del 30% en la prevención de la muerte o la hospitalización.

Dado que funciona mediante la inducción de errores genéticos, las directrices estadounidenses recomiendan que se utilice sólo cuando otros tratamientos ambulatorios, incluido el Paxlovid de Pfizer Inc. (PFE), no estén disponibles.

Los hallazgos “proporcionan una confianza adicional en el potencial de molnupiravir como una importante opción de tratamiento para ciertos adultos con COVID-19 de leve a moderada que están en alto riesgo de continuar hacia una enfermedad grave”, dijo Dean Li, presidente de Merck Research Laboratories, en el comunicado.

El regulador de la Unión Europea todavía está revisando el medicamento.

El molnupiravir es el nombre químico de un medicamento desarrollado originalmente para tratar la gripe que se administra por vía oral en una cápsula. Inhibe la replicación del SARS-CoV-2, el coronavirus que causa el COVID-19, mediante un mecanismo conocido como “mutagénesis letal”. En términos sencillos, hace que la maquinaria que reproduce el material genético del virus cometa errores, haciendo que las copias sean defectuosas. El fármaco fue descubierto en la Universidad Emory de Atlanta y está siendo desarrollado por Merck, con sede en Kenilworth (Nueva Jersey), y Ridgeback Biotherapeutics, con sede en Miami.

El análisis provisional de los datos de un ensayo aleatorio reveló que reduce el riesgo de hospitalización en aproximadamente un 50%, según informó el laboratorio en un comunicado del 1 de octubre. De 385 pacientes que recibieron el fármaco, 28 (7,3%) fueron hospitalizados, frente a 53 de 377 (14,1%) que recibieron un placebo. Hasta el día 29, no se registraron muertes en los pacientes que recibieron molnupiravir, pero ocho murieron en el brazo del placebo.

Una de las diferencias que tiene con otros medicamentos es que, por ejemplo el remdesivir antiviral de Gilead, así como los anticuerpos monoclonales, se administran mediante una infusión intravenosa. Esto suele hacerse en un hospital o una clínica, donde las personas infectadas corren el riesgo de transmitir el virus al personal médico y a otros pacientes. La principal ventaja del molnupiravir es que se toma en forma de píldora, lo que permite a los pacientes ser tratados en casa. También es probable que sea más barato: Un tratamiento de cinco días de molnupiravir costará unos 700 dólares por paciente, un tercio del coste de un tratamiento con anticuerpos monoclonales, según el New York Times.

En tanto, tiene similitudes con el antiviral Paxlovid, de Pfizer, que también es un tratamiento en píldoras para enfermos que pueden desarrollar un cuadro grave de COVID-19.

Los adultos con COVID-19 de leve a moderado tomaron Molnupiravir por vía oral cada 12 horas durante cinco días. Todavía se están realizando estudios para determinar el régimen más eficaz. Un estudio realizado en 2021 demostró que el molnupiravir tenía poco efecto cuando se administraba a pacientes ya hospitalizados con la enfermedad grave. Un estudio está probando si puede utilizarse para prevenir la propagación del SARS-CoV-2 en hogares en los que uno o más miembros tienen COVID-19.

Merck and Ridgeback’s Molnupiravir, an Investigational Oral Antiviral COVID-19 Medicine, Demonstrated Activity Against Omicron Variant in In Vitro Studies

KENILWORTH, N.J. & MIAMI–(BUSINESS WIRE)– Merck (NYSE: MRK), known as MSD outside the United States and Canada, and Ridgeback Biotherapeutics today announced data from six preclinical studies demonstrating that molnupiravir, an investigational oral antiviral COVID-19 medicine, was active against the SARS-CoV-2 variant Omicron (B1.1.529) in vitro.

“These findings from multiple independent in vitro studies showing that molnupiravir has consistent antiviral activity against Omicron, the primary variant circulating globally, provide additional confidence in the potential of molnupiravir as an important treatment option for certain adults with mild to moderate COVID-19 who are at high risk for progressing to severe disease,” said Dr. Dean Y. Li, president, Merck Research Laboratories. “We are grateful to these investigators for these important insights, and to our own colleagues who are working with global regulatory authorities to ensure that molnupiravir is widely accessible to appropriate patients.”

The in vitro studies were independently conducted by researchers from institutions in six countries including Belgium, Czech Republic, Germany, Poland, the Netherlands and the United States. The studies used established cell-based assays to evaluate the antiviral activity of molnupiravir and other COVID-19 antiviral agents against SARS-CoV-2 variants of concern, including Omicron. Molnupiravir has yet to be studied against Omicron in clinical studies. For additional information about the preclinical studies, please see the endnote.

“Based on its mechanism of action, along with these new findings demonstrating in vitro activity across multiple variants, including Omicron, we anticipate that molnupiravir will continue to be active against variants of concern and an important tool in the fight against COVID-19,” said Wendy Holman, chief executive officer, Ridgeback Biotherapeutics. “We are grateful for the efforts of the investigators and look forward to continuing our work to help address the pandemic.”

Merck is developing molnupiravir in collaboration with Ridgeback Biotherapeutics and it has been authorized for use in more than 10 countries, including in the United States, United Kingdom and Japan.

Other Variants of Concern

Findings from the Phase 3 MOVe-OUT study were published in the New England Journal of Medicine, as previously announced. In MOVe-OUT, the efficacy of molnupiravir treatment was generally consistent across important patient subgroups, including patients infected with SARS-CoV-2 variants of concern, Delta, Gamma, and Mu. Among the all-randomized population with viral sequencing data available (55.3%), the three most common SARS-CoV-2 variants were Delta (58.1%), Mu (20.5%), and Gamma (10.7%).

About Merck’s Global Efforts to Accelerate Access to Molnupiravir Following Regulatory Authorizations or Approvals

Global access has been a priority for Merck and Ridgeback since the inception of their molnupiravir collaboration. The companies are committed to providing timely access to molnupiravir globally through our comprehensive supply and access approach, which includes investing at risk to produce millions of courses of therapy; tiered pricing based on the ability of governments to finance health care; entering into supply agreements with governments; allocating up to 3 million courses of therapy for distribution through UNICEF and the ACT Accelerator Therapeutics Partnership; and granting voluntary licenses to generic manufacturers and to the Medicines Patent Pool to make generic molnupiravir available in more than 100 low- and middle-income countries following local regulatory authorizations or approvals.

Supply: In anticipation of the results from MOVe-OUT and the potential for regulatory authorization or approval, Merck produced molnupiravir at risk, manufacturing 10 million courses of treatment by the end of 2021, with at least 20 million courses expected to be produced in 2022. To date, Merck has shipped molnupiravir to over 20 countries, including 2 million patient courses shipped to the U.S. Government; in countries where it is approved or authorized, patients have begun to receive the drug. To supplement the supply from licensed generic manufacturers, Merck has entered an agreement with UNICEF to allocate up to 3 million courses of therapy to low- and middle-income countries through the first half of 2022.

Supply agreements: Merck entered into a procurement agreement with the U.S. Government under which the company will supply approximately 3.1 million courses of molnupiravir to the U.S. Government, upon Emergency Use Authorization or approval from the U.S. Food and Drug Administration. The U.S. Department of Health and Human Services (HHS) has created a website to help providers locate public locations that have received shipments of Government-procured COVID-19 therapeutics available under Emergency Use Authorization. Merck has also entered into advance purchase and supply agreements for molnupiravir with governments for over 30 markets worldwide, including Australia, Canada, Korea, Japan, Thailand, United Kingdom and United States, pending regulatory authorizations, and is currently in discussions with additional governments. Merck is implementing a tiered pricing approach based on World Bank country income criteria to reflect countries’ relative ability to finance their health response to the pandemic.

Voluntary licenses: As part of its commitment to widespread global access, Merck previously announced that it has entered into a licensing agreement with the Medicines Patent Pool to increase broad access for molnupiravir in low- and middle-income countries. Additionally, Merck previously announced that the company has entered into non-exclusive voluntary licensing agreements for molnupiravir with established generic manufacturers to accelerate availability of molnupiravir in more than 100 low- and middle-income countries following approvals or emergency authorization by local regulatory agencies.

Merck continues to discuss additional measures and collaborations to accelerate broad, global access to molnupiravir.

Authorized Use of Molnupiravir in the U.S.

The U.S. Food and Drug Administration (FDA) has issued an EUA for the emergency use of the unapproved molnupiravir, a nucleoside analogue that inhibits SARS-CoV-2 replication by viral mutagenesis, for the treatment of mild to moderate coronavirus disease 2019 (COVID-19) in adults with positive results of direct SARS-CoV-2 viral testing, and who are at high risk for progression to severe COVID-19, including hospitalization or death, and for whom alternative COVID-19 treatment options authorized by FDA are not accessible or clinically appropriate. Molnupiravir is not FDA-approved for any use including for use for the treatment of COVID-19. Prior to initiating treatment with molnupiravir, carefully consider the known and potential risks and benefits.

Molnupiravir is authorized only for the duration of the declaration that circumstances exist justifying the authorization of the emergency use of molnupiravir under section 564(b)(1) of the Federal, Food, Drug, and Cosmetic Act, 21 U.S.C. § 360bbb-3(b)(1), unless the authorization is terminated or revoked sooner.

Molnupiravir is not authorized for use in patients less than 18 years of age or who are hospitalized due to COVID-19. Benefit of treatment with molnupiravir has not been observed in subjects when treatment was initiated after hospitalization due to COVID-19. Molnupiravir is not authorized for use for longer than five consecutive days. Molnupiravir is not authorized for pre-exposure or post-exposure prophylaxis for prevention of COVID-19. Molnupiravir may only be prescribed for an individual patient by physicians, advanced practice registered nurses, and physician assistants that are licensed or authorized under state law to prescribe drugs in the therapeutic class to which molnupiravir belongs (i.e., anti-infectives).

Selected Safety Information for Molnupiravir

Contraindications

No contraindications have been identified based on the limited available data on the emergency use of molnupiravir authorized under this EUA.

Adverse Reactions

The most common adverse reactions occurring in ≥1% of subjects in the molnupiravir treatment group in the Phase 3 double-blind MOVe-OUT study were diarrhea (2% versus placebo at 2%), nausea (1% versus placebo at 1%), and dizziness (1% versus placebo at 1%) all of which were Grade 1 (mild) or Grade 2 (moderate).

Serious adverse events occurred in 7% of subjects receiving molnupiravir and 10% receiving placebo; most serious adverse events were COVID-19 related. Adverse events leading to death occurred in 2 (<1%) of the subjects receiving molnupiravir and 12 (2%) of subjects receiving placebo.

Drug Interactions

No drug interactions have been identified based on the limited available data on the emergency use of molnupiravir. No clinical drug-drug interaction trials of molnupiravir with concomitant medications, including other treatments for mild to moderate COVID-19, have been conducted.

Pregnancy/Breastfeeding

There are no data on the presence of molnupiravir or its metabolites in human milk. It is unknown whether molnupiravir has an effect on the breastfed infant or effects on milk production. Based on the potential for adverse reactions in the infant from molnupiravir, breastfeeding is not recommended during treatment with molnupiravir and for 4 days after the final dose. A lactating individual may consider interrupting breastfeeding and may consider pumping and discarding breast milk during treatment and for 4 days after the last dose of molnupiravir.