FDA Limits GSK's Xevudy Authorization Due to BA.2 Variant Concerns
The U.S. Food and Drug Administration has scaled back the emergency use authorization (EUA) for GlaxoSmithKline and Vir Biotechnology's COVID-19 antibody therapy Xevudy (sotrovimab), citing new data indicating reduced effectiveness against the emerging BA.2 Omicron subvariant.
The regulatory restriction applies specifically to Health and Human Services (HHS) regions where BA.2 is becoming the dominant SARS-CoV-2 strain. Currently, the limitations affect region 1 (Connecticut, Maine, Massachusetts, New Hampshire, Rhode Island, and Vermont) and region 2 (New Jersey, New York, Puerto Rico, and the Virgin Islands).
Impact on Treatment Guidelines
The development marks another setback in the COVID-19 antibody therapy landscape. Earlier, the FDA had withdrawn authorization for Eli Lilly's bamlanivimab/etesevimab combination and Regeneron's REGEN-COV when data showed their diminished efficacy against the original BA.1 Omicron variant.
Current National Institutes of Health (NIH) treatment guidelines prioritize COVID-19 therapeutics in the following order:
- Pfizer's Paxlovid (nirmatrelvir/ritonavir)
- GSK/Vir's Xevudy
- Gilead's Veklury (remdesivir)
- Merck & Co/Ridgeback Bio's Lagevrio (molnupiravir)
Clinical Efficacy and Commercial Impact
Xevudy initially received its EUA in May 2021 based on impressive phase 3 results, demonstrating a 79% reduction in risk of hospitalization or death compared to placebo in patients with mild-to-moderate COVID-19. The therapy has since become a significant revenue generator for GSK, contributing approximately $1.25 billion to the company's 2021 revenues, with similar projections for 2022.
The U.S. government had previously committed around $1 billion for an estimated 750,000 doses of Xevudy.
Development of Higher Dose Formulation
GSK and Vir have responded proactively to the BA.2 challenge, announcing their work on a higher dose formulation of Xevudy. The companies believe this new formulation will effectively combat the BA.2 subvariant and plan to share supporting data with global regulatory authorities. Despite the current setback, they maintain their timeline for seeking full regulatory approval this year.
Emerging Alternative: AstraZeneca's Evusheld
As Xevudy faces challenges, AstraZeneca's Evusheld (tixagevimab/cilgavimab) has secured EU approval for pre-exposure prophylaxis of COVID-19. The long-acting antibody combination demonstrated 77% efficacy in preventing symptomatic COVID-19 compared to placebo in the PROVENT phase 3 trial, with protection lasting at least six months. Notably, Evusheld has shown retained neutralizing activity against the BA.2 variant.
Dr. Christoph Spinner from University Hospital Rechts der Isar in Germany emphasized the timing of this approval: "Increasing COVID-19 cases, driven by the highly-transmissible BA.2 subvariant, and withdrawal of several pandemic public health measures make it important to protect vulnerable populations, such as the immunocompromised, from SARS-CoV-2 infection."