Early Use of Monoclonal Antibodies Deemed Important for Effectiveness
In an update on October 26, Eli Lilly stated that the pause of the ACTIV-3 trial was made permanent. The reason was not a safety issue with the antibody treatment – i.e. unanticipated side effect – but rather that it was ineffective on patients already hospitalized with advanced COVID-19. Given our understanding of how antibody-based treatments work, as well as the many complications that become involved in late-stage COVID-19 which no longer involve the virus directly, this is not a surprising result.
Dr. Eric Topol, a clinical trial expert at the Scripps Research Institute who has been following the treatment’s development, said the news “tells us they stopped the trial due to futility, as suspected,” and that it “suggests that the timing of monoclonal antibody administration — early — will be important.”New York Times: By Katherine J. Wu and Katie Thomas
Here is Eli Lilly’s statement:
The ACTIV-3 clinical trial is being run by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), and is the only study evaluating the efficacy of bamlanivimab in hospitalized COVID-19 patients. Based on an updated dataset from the trial reviewed on October 26, no additional COVID-19 patients in this hospitalized setting will receive bamlanivimab. This recommendation was based on trial data suggesting that bamlanivimab is unlikely to help hospitalized COVID-19 patients recover from this advanced stage of their disease. In this updated dataset, differences in safety outcomes between the groups were not significant.
All other studies of bamlanivimab remain ongoing, including ACTIV-2, the NIH-sponsored study in recently diagnosed mild to moderate COVID-19 patients; BLAZE-1, Lilly’s ongoing Phase 2 trial in people recently diagnosed with COVID-19 in the ambulatory (non-hospitalized) setting, studying bamlanivimab as monotherapy and in combination with etesevimab; and BLAZE-2, Lilly’s Phase 3 study of bamlanivimab for the prevention (prophylaxis) of COVID-19 in residents and staff at long-term care facilities. Based on data from BLAZE-1, Lilly submitted a request for EUA for bamlanivimab for the treatment of recently diagnosed mild to moderate COVID-19 illness in high-risk patients to the U.S. FDA in early October.
While there was insufficient evidence that bamlanivimab improved clinical outcomes when added to other treatments in hospitalized patients with COVID-19, we remain confident based on data from Lilly’s BLAZE-1 study that bamlanivimab monotherapy may prevent progression of disease for those earlier in the course of COVID-19.Lilly Statement Regarding NIH’s ACTIV-3 Clinical Trial, October 26, 2020