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Omicron subvariant, BA.2, poses a serious threat to the efficacy of current therapies

says GlobalData

More research is required to determine whether current Omicron treatments are effective against BA.2—the most transmissible of the Omicron subvariants, says GlobalData. The leading data and analytics company notes that vaccines and therapies should be tested specifically against BA.2 to better prepare for challenges that may lay ahead. BA.2 contains numerous unique mutations compared to its predecessor that may allow it to circumvent immunization and treatment efforts.

Nancy Jaser, PharmD/MBA, Infectious Diseases Analyst at GlobalData, comments: “Early studies suggest that GlaxoSmithKline’s sotrovimab may face a steep 27-fold* drop in efficacy against BA.2 compared with the original Omicron strain, BA.1. BA.2 does not contain a major mutation in the spike protein that is present in BA.1 (deletion Δ69-70)** and may be linked to how BA.2 escapes sotrovimab therapy. With sotrovimab now at risk for becoming the third limited mAb, drug developers should focus on newer therapies with viral targets outside of the frequently mutated spike protein.”

New variants tend to evolve in ways that evade mAb therapies, as seen when the emergence of Omicron (BA.1) resulted in the Food and Drug Administration (FDA) restricting the use of two mAb treatments, Regeneron’s REGN-COV2 and Eli Lilly’s LY-CoV555/LY-CoV016, as their efficacy decreased. This subvariant evolved to contain 28*** unique mutations not found in Omicron. This large number of advanced mutations found in BA.2 raises many concerns, as these adaptations may potentially change how the virus is affected by vaccines, drugs, and how it presents clinically.

Jaser notes: “The two most recently approved mAbs, AstraZeneca’s Evusheld** and Eli Lilly’s bebtelovimab****, demonstrated good efficacy against BA.2 and are currently available for use. However, it is unclear if they will retain efficacy as BA.2 becomes more dominant and larger studies are conducted.”

Other available non-mAb therapeutic options in the present Omicron/BA.2 landscape include Pfizer’s Paxlovid, Gilead’s remdesivir, and Merck’s molnupiravir. However, if BA.2 has significantly shifted away from the original variant, the authorization of these treatments is also subject to change.

Jaser adds: “Developing treatments for COVID-19 that retain efficacy even as the virus continues to mutate remains an important unmet need. With BA.2 already spreading across 92* countries at a rate 1.5*** times faster than its parent, it may soon take over as the dominant COVID-19 variant worldwide.”

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