Biopharmaceutical company Atriva Therapeutics GmbH, a pioneer in the development of antiviral therapies targeting host cells, presents results showing high efficacy of its lead compound zapnometinib, which is in advanced clinical development, against the omicron strain of SARS-CoV-2.
„I am very pleased that we were able to rapidly demonstrate antiviral activity of zapnometinib in our laboratories following the emergence of the Omikron variant. This strong efficacy has now been confirmed externally by a CRO services in Rotterdam. Our results provide strong evidence for universal efficacy of zapnometinib against coronavirus variants of concern,“ said Prof. Oliver Planz, M.D., CSO of Atriva Therapeutics.
„Omikron highlights the limitations of antiviral monoclonal antibody therapy in COVID-19 – a clear opportunity for host cell targeted drugs like zapnometinib. Atriva is currently conducting a Phase 2 trial in hospitalized patients with moderate-to-severe COVID-19 infection. From this study, we expect to generate data that will demonstrate the broad therapeutic potential of our lead compound, zapnometinib. Zapnometinib is a dual-effect MEK inhibitor that is expected to be effective against all existing variants of SARS-CoV-2. In addition, zapnometinib is not susceptible to antiviral resistance, which compromises the efficacy of monoclonal antibodies,“ commented Stephan Stenglein, M.D., CMO of Atriva Therapeutics.
The Omikron variant has more than 30 mutations at the spike protein compared to earlier variants such as Delta. These mutations are associated with increased infectivity and allow escape from a patient’s antibody immune response acquired through vaccination or infections that have already occurred („escape mutations“). Although the Omikron variant is comparatively less pathogenic than earlier variants such as Delta, it still poses a potentially lethal risk to patients who cannot be vaccinated or have a combination of risk factors such as advanced age or immunodeficiency. Because of the high number of escape mutations in Omikron, previous coronavirus vaccines may be less effective against this variant of SARS-CoV-2.
Partial or complete loss of efficacy is also seen with almost all of the pre-approved monoclonal antibody (MAb) therapies. Current guidelines from the NIH COVID-19 treatment panel include only two MAb therapies: Sotrovimab (Vir/GSK, limited availability) and Bebtelovimab (Eli Lilly, as the last possible treatment option). More recently, the U.S. FDA further restricted the use of sotrovimab because it is ineffective against the widely used BA.2 subvariant of Omikron. Other MAb therapies-including casirivimab/imdesimab (Regeneron)-are not considered effective against the current variant and are unlikely to have relevant clinical treatment effects in future variants of SARS-CoV-2.
MAb therapies in patients with COVID-19 primarily target the spike protein on the surface of SARS-CoV-2, which mediates attachment of the virus to the host cell and is an important target of the host adaptive immune response. The problematic loss of efficacy of MAbs against new strains of SARS-CoV-2 underscores the importance of new therapeutic approaches such as zapnometinib, which is able to maintain potent efficacy against all viral strains including omicron.