COVID-19: Merck Withdraws EMA Application for LAGEVRIO

On June 21st, Merck (MSD) submitted a letter to the Committee for Medicinal Products for Human Use (CHMP) announcing their decision to withdraw the marketing authorization application of LAGEVRIO (oral, direct-acting antiviral, 800 mg LAGEVRIO BID for 5 days, generic name molnupiravir) for the treatment of COVID-19 in adults who do not require supplemental oxygen and who are at increased risk of developing severe COVID-19 in the European Union.

Attached are Merck’s letter to the CHMP and an EMA Q&A guide for LAGEVRIO’s withdrawal. Merck has not issued a press release on LAGEVRIO’s withdrawal at this time.

Key Highlights from the European Medicines Agency:

• Merck withdrew their marketing authorization application prior to the completion of the re-examination process of the Agency’s negative recommendation of LAGEVRIO. The decision was based on “CHMP’s view that the data provided do not allow the committee to conclude on a positive benefit-risk balance” for LAGEVRIO.
• The CHMP previously concluded the clinical benefit of LAGEVRIO in adults had not been demonstrated and recommended the refusal of marketing authorization. Merck requested the CHMP re-examination in March.
• Merck continues to note their disagreement with the CHMP’s assessment in their letter, noting their belief the Ph3 MOVe-OUT trial is sufficient in supporting a positive benefit-risk assessment for LAGEVRIO in treating adults with COVID-19. The letter also notes Merck’s rights for further submissions to the EMA for LAGEVRIO in COVID-19 or other therapeutic indications.
• Reuters reported the current research head of Merck, Dean Li, stated the company is “evaluating [their] options on how [they] can generate additional evidence supportive of LAGEVRIO for the treatment of COVID-19” and they are committed to providing LAGEVRIO through “compassionate or emergency use programs”

CI Assessment:

• LAGEVRIO has remained listed as an EMA Article 5(3) medicine, but use of LAGEVRIO substantially decreased following the initial CHMP recommendation to not grant marketing authorization to the therapy. Merck’s formal withdrawal of LAGEVRIO’s application may result in further decline of LAGEVRIO use, subsequently reinforcing PAXLOVID’s (oral, protease inhibitor, 300mg nirmatrelvir boosted with 100mg ritonavir) position as the preferred oral antiviral in Europe. This also leaves an opportunity for obeldesivir to differentiate from PAXLOVID as an oral antiviral treatment without DDI risks.
• It remains to be seen if this update will impact the regulatory status or use of LAGEVRIO in markets with higher utilization rates of LAGEVRIO (e.g., Japan).
• Merck may have withdrawn its application after determining the CHMP’s re-examination would likely lead to another negative opinion, thus avoiding subsequent negative publicity.