Humanigen Inc (HGENQ)

[DonDonDonDon]

LENZILUMAB IN HOSPITALIZED BLACK/AFRICAN-AMERICAN COVID-19 PATIENTS: LIVE-AIR PHASE 3 STUDY RESULTS

https://journals.lww.com/ccmjournal/Fulltext/2022/01001/23__LENZILUMAB_IN_HOSPITALIZED.26.aspx

Background: Black/African Americans (B/AA) are twice as likely as Whites to develop COVID-19, possibly due to disparities in healthcare access and genetics. Mutations in the angiotensin converting enzyme gene enabling greater SARS-CoV-2 replication may be overexpressed in B/AAs leading to increased viral load, morbidity, hospitalizations, and mortality. The hyperinflammatory cytokine storm accompanying SARS-CoV-2 infection is mediated by GM-CSF releasing downstream inflammatory chemokines, cytokines, and inflammatory markers including C-reactive protein (CRP), predictive of clinical worsening. This analysis of LIVE-AIR explored the efficacy of lenzilumab in its B/AA population.

Methods: LIVE-AIR was a randomized, double-blind, placebo-controlled trial of 479 (mITT population) hospitalized COVID-19. Patients, ≥18 years old with oxygen saturation ≤94% on room air or requiring supplemental oxygen (low-flow or high-flow), but not invasive mechanical ventilation, were randomized to receive lenzilumab (1800?mg, n=236) or placebo (n=243) via three IV infusions, every 8 hours, within 12 hours of randomization. A secondary analysis of the primary endpoint, survival without ventilation (SWOV), by race/ethnicity and baseline CRP level was assessed at Day 28.

Results: Participants were racially and ethnically diverse: 3.1% Asians, 14.8% B/AA, 38.6% Hispanic/Latino. The likelihood of SWOV was significantly improved by lenzilumab across races and ethnicities compared with placebo (HR: 1.54; 95% CI: 1.02, 2.32; p=0.0403; N=479) and in patients with baseline CRP< 150?mg/L, < 85 years of age (HR 3.04; 1.68, 5.51; p=0.0003; n=337). The likelihood of SWOV in B/AAs trended higher than the overall population (HR: 2.68; 0.89-8.12; p=0.0811; n=71) and was significantly and disproportionately improved in those with baseline CRP< 150?mg/L (HR: 8.96; 1.09-73.55; p=0.0412; n=51). Serious adverse events were similar across treatment groups.

Conclusion: In LIVE-AIR, with a B/AA representation comparable to the US population and usually under-represented in trials, lenzilumab improved the likelihood of SWOV across races and ethnicities of COVID-19 patients; however, B/AA with baseline CRP< 150?mg/L exhibited a markedly greater improvement. Biological, genetic, and social factors contributing to these differences requires further investigation.