COVID-19 Wins and Losses: Genentech’s Actemra Flunks Trial; Vir & GSK’s Antibody Dazzles

Coronavirus

It’s a good news/bad news kind of day, as Genentech reported its rheumatoid arthritis drug Actemra failed to hit its primary endpoint in a COVID-19 trial, while Vir and GlaxoSmithKline’s antibody against COVID-19 demonstrated 85% efficacy. This was such a positive result the independent Data Monitoring Committee recommended they halt it early and file for Emergency Use Authorization (EUA).

Genentech’s Actemra Flunks COVID-19 Trial

Genentech, a Roche company, announced that its Phase III REMDACTA trial of Actemra (tocilizumab) plus Gilead Sciences’ Veklury (remdesivir) compared to placebo plus Veklury, failed to meet its primary endpoint in patients with severe COVID-19 pneumonia. The endpoint was measured by improved time to hospital discharge up to day 28 in this patient group receiving standard of care.

“Given the global impact of COVID-19 pneumonia on patients, we are disappointed that the REMDACTA study did not meet its endpoints,” said Levi Garraway, chief medical officer and head of Global Product Development for Genentech. “We continue to believe that the totality of data suggests a potential role for Actemra in treating certain patients with COVID-19 and will discuss the results with health authorities. We thank our partners at Gilead, and all the patients, investigators and healthcare professionals for their participation.”

Genentech is still evaluating data from REMDACTA, COVACTA and EMPACTA trials in addition to other studies of Actemra in COVID-19 pneumonia. The EMPACTA study hit its primary endpoint, but COVACTA did not. Both were recently published in the New England Journal of Medicine. EMPACTA evaluated minority patients in hospitalized COVID-19 pneumonia. COVACTA evaluated intravenous Actemra with standard of care in adults hospitalized with severe COVID-19 pneumonia.

Actemra is a humanized interleukin-6 (IL-6) receptor antagonist indicated for adults with moderately to severely active rheumatoid arthritis who have used one or more antirheumatic drugs, such as methotrexate, that did not provide enough relief.

Vir and GlaxoSmithKline’s VIR-7831 Dramatically Decreased Hospitalization and Risk of Death in COVID-19

Vir Biotechnology and GlaxoSmithKline announced that an independent Data Monitoring Committee (IDMC) recommend their Phase III COMET-ICE trial of VIR-7831 as a monotherapy for early treatment of COVID-19 in adults at high risk be stopped for enrollment “due to evidence of profound efficacy.” The recommendation was based on interim analysis of data from 583 patients in the trial showing an 85% decrease in hospitalization or death in patients receiving the drug alone compared to placebo, which was the primary endpoint of the trial. The drug was well tolerated.

VIR-7832 is an investigational dual-action SARS-CoV-2 monoclonal antibody. It appears to both block viral entry into healthy cells and improve the ability to clear infected cells. The antibody binds to an epitope on SARS-CoV-2 that is shared with SARS-CoV-1, the virus that causes SARS, suggesting it is highly conserved, and hopefully will make it more difficult for resistance to develop.

The trial is ongoing and blinded with patients to be followed for 24 weeks. Based on this data, the companies plan to submit an Emergency Use Authorization (EUA) to the U.S. Food and Drug Administration (FDA) and for authorization in other countries. The data will also be the foundation for a Biologics License Application (BLA) submission to the FDA.

They also announced data from a new trial that is on bioRxiv, but has not yet been peer-reviewed. This research demonstrated that the drug maintained activity against current circulating variants, including the UK, South African and Brazilian mutations. This was based on in vitro data from pseudotyped virus assays.

Additional trials of VIR-7831 include COMET-PEAK, a Phase II in low-risk adults and mild to moderate COVID-19; COMET-TAIL, a Phase III that hasn’t begun yet, but is expected to start in the third quarter of 2021 in high-risk adults to evaluate if intramuscular administration can decrease hospitalization or death from COVID-19; and the Phase III COMET-STAR trial to begin in the second quarter in uninfected adults at high risk.

“These exciting data with a single antibody against a conserved epitope bring us one step closer to delivering an effective solution to patients around the globe,” said George Scangos, chief executive officer of Vir. “The dual-action design of VIR-7831 to both block viral entry into healthy cells and clear infected cells, as well as its high barrier to resistance, are key distinguishing characteristics.”

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