Humanigen, announced positive interim Phase 3 data of lenzilumab in patients hospitalised with COVID-19. This interim analysis for sizing and powering suggests that lenzilumab had a clinically meaningful impact on patient recovery, with an estimated 37 per cent more recoveries observed in the lenzilumab arm of the randomised, placebo-controlled, double-blinded study versus current standard of care (SOC).
The data safety monitoring board (DSMB) composed of independent subject matter experts conducted an interim analysis of the unblinded data for trial sizing and powering and recommended increasing the target number of events (recoveries) from 257 to 402 to maintain the power of the study at 90 percent. The adaptive trial design only allows for the addition of patients if interim data are in the “promising zone” (i.e., achieving or surpassing an average improvement in recoveries of 29 percent (hazard ratio (HR) > 1.29) through day 28).
The company remains blinded to the data and based on the recommended number of events, the HR was calculated to be 1.37, an average of 37 percent more recoveries observed in the lenzilumab arm compared to the control arm. Any observed benefit in the lenzilumab arm would be over and above the use of remdesivir and/or steroids which are among the treatments that have been used as SOC in both the lenzilumab treatment arm and the placebo arm of the study.
At the recommendation of the DSMB, the company plans to increase enrollment to achieve 402 events (approximately 515 patients). This increase in enrollment ensures an even higher probability of success in meeting the primary endpoint and maintains the power of the study at 90 percent. The next interim analysis for efficacy is planned when the study reaches 75 percent events (302 events) which will require approximately 390 patients to be enrolled in the trial.
“Based on this feedback from the DSMB, we believe the Phase 3 trial is significantly de-risked. Targeting 402 events improves the probability of success, maintains the power of the study at 90 per cent, and further supports our plans for Emergency Use Authorization (EUA) and Biologics License Application (BLA) submission. We are working to quickly activate additional trial sites across the US to support rapid enrollment and increase access to lenzilumab with a continued commitment to inclusion and diversity,” said Dale Chappell, chief scientific officer of Humanigen. “”
A Cooperative Research and Development Agreement (CRADA) that Humanigen entered into with the Joint Program Executive Office for Chemical, Biological Radiological and Nuclear Defense (JPEO-CBRND), provides for, among other support, regulatory, statistical and manufacturing subject matter advice to anticipation of an application for an EUA and eventually a BLA submission. The activities under the CRADA are being funded by the Biomedical Advanced Research and Development Authority (BARDA), part of the Office of the Assistant Secretary for Preparedness and Response (ASPR) at the U.S. Department of Health and Human Services (HHS), working in collaboration with JPEO-CBRND. These activities include providing regulatory representatives who may participate in informal or formal meetings with the U.S. Food and Drug Administration (FDA) and providing comments on submission prior to submitting to FDA.
Humanigen intends to file for EUA in the first quarter of 2021 either following interim data at 75 percent or at study completion. The Phase 3 trial evaluating patients hospitalised with COVID-19 is enrolling at sites across the US and Latin America. Current enrollment stands at 300 patients.
Interim Phase 3 lenzilumab in COVID-19 data analysis highlights:
· 78 per cent of trial participants on either remdesivir or dexamethasone (or other steroids) or both (across both arms of the study)
· 65 per cent of trial participants with oxygen saturation 94 per cent or on low-flow oxygen support
· 35 per cent of trial participants on high-flow oxygen or non-invasive positive pressure ventilation at time of enrollment
· 45 per cent of trial participants were 65 years of age or older
· 50 per cent of trial participants from diverse populations
· No serious adverse events have been attributed to lenzilumab
· These findings apply across both arms of the study