Benefit of GSK, Vir's monoclonal antibody unclear in hospitalised COVID-19 patients

GlaxoSmithKline and Vir Biotechnology announced Wednesday that an arm of the ACTIV-3 study investigating VIR-7831 in hospitalised adults with COVID-19 will be closed to enrolment as the benefit of the dual-action SARS-CoV-2 monoclonal antibody may be less than expected. George Scangos, chief executive of Vir, whose shares plunged as much as 30% on the news, remarked "we are disappointed with the recommendation" of the independent data and safety monitoring board (DSMB).

A sub-study of the US National Institutes of Health's (NIH) ACTIV-3 trial began in December last year evaluating VIR-7831, initially recruiting 300 participants who had been hospitalised with mild-to-moderate COVID-19 with fewer than 13 days of symptoms. In the study, subjects also received standard care for COVID-19, including Gilead Sciences' antiviral Veklury (remdesivir). The trial's primary efficacy endpoint is the participants' sustained recovery for 14 days after release from the hospital, with subjects followed for 90 days after enrolment to analyse their response to treatment.

"Concerns" over magnitude of benefit

GlaxoSmithKline and Vir said that while VIR-7831 met the "initial pre-specified criteria to continue to the next phase of the ACTIV-3 trial and there were no reported safety signals, sensitivity analyses of the available data raised concerns about the magnitude of potential benefit." The DSMB noted that the closure of the study arm will allow the data to mature.

The companies said they will continue discussions with the NIH about ways to further assess the potential of VIR-7831 in the hospitalised population. In addition to the ACTIV-3 trial, VIR-7831 is also being evaluated in the outpatient setting in the Phase III COMET-ICE and Phase II BLAZE-4 studies. Further, VIR-7831 is being investigated, along with the dual-action SARS-CoV-2 monoclonal antibody VIR-7832, in the Phase Ib/IIa AGILE trial in adults with mild-to-moderate COVID-19.

Latest setback for GSK

GlaxoSmithKline and Vir entered into a collaboration last year to develop antiviral antibodies for coronaviruses, including SARS-CoV-2, with the partnership expanded in February to include new therapies for influenza and other respiratory viruses. Meanwhile, GlaxoSmithKline is also investigating otilimab in COVID-19, with the company recently announcing plans to narrow its focus on the elderly after the anti-GM-CSF monoclonal antibody showed signs of benefit in the Phase IIa OSCAR trial when added to standard care among patients ≥70 years hospitalised with severe COVID-19-related pneumonia, but not in the overall study population.

The UK drugmaker also has partnerships with CureVac and Sanofi focused on developing vaccines against coronaviruses. Last month, GlaxoSmithKline and Sanofi started a new Phase II study aimed at selecting the most appropriate antigen dosage of their adjuvanted, recombinant, protein-based COVID-19 vaccine candidate. The companies were previously forced to delay development of their vaccine programme after an earlier Phase I/II study showed a low immune response in older adults.

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