Mavrilimumab linked to 65% reduced risk for mortality, ventilation in severe COVID-19
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A single dose of the granulocyte/macrophage-colony stimulating factor antibody mavrilimumab was linked to reduced mortality and mechanical ventilation in patients hospitalized for severe COVID-19, according to a speaker at the EULAR 2021 Congress.
“The cytokine GM-CSF is vital to both lung homeostasis and regulation of inflammation in autoimmunity,” Lara Pupim, MD, MSCI, vice president of clinical research and development at Kiniksa Pharmaceuticals, told attendees. “[GM-CSF] may contribute to respiratory failure and death in patients with COVID-19 pneumonia and inflammation.”
The human monoclonal antibody mavrilimumab (Kiniksa Pharmaceuticals) has previously shown the capacity to block signaling of this cytokine and downregulate inflammatory processes in other conditions, according to Pupim.
In the current ongoing, global, randomized, double-blind, placebo-controlled transition phase 2/3 trial, the researchers aimed to assess the clinical outcomes for the drug in patients hospitalized with severe COVID-19-associated pneumonia and systemic hyperinflammation.
Being alive and free of ventilation at day 29 served as the primary outcome measure. The group also assessed time to clinical improvement, time to return to room air and mortality at the same time point.
Pupim reported findings for the first of two cohorts. The findings she presented included data for 116 patients accrued in the U.S., Brazil, Chile, Peru and South Africa.
Treatment with 10 mg/kg or 6 mg/kg mavrilimumab or placebo was randomly assigned within 48 hours of randomization. Importantly, 96% of patients were also receiving corticosteroids and nearly one-third were receiving remdesivir (Veklury, Gilead Sciences) as standard of care for COVID-19.
No differences were reported in outcomes for the two doses of mavrilimumab. “The results presented here are pooled from both mavrilimumab groups,” Pupim said.
However, the findings showed that 86.7% of patients treated with the study drug and 74.4% of those treated with placebo were alive and off ventilation at day 29, a difference of 12.3 percentage points (P = .1224), according to Pupim.
A 65% reduction in risk for ventilation or mortality was observed at day 29 in patients treated with mavrilimumab compared with placebo (HR = 0.35; P = .0175). “Separation in the Kaplan-Meier curves was evident very early after study drug administration,” Pupim said.
Mortality rates at day 29 were 8% for mavrilimumab and 20.5% for placebo, a difference of 12.5 percentage points (P = .0718), according to the findings. A 61% reduction in mortality risk was reported for patients treated with mavrilimumab vs. placebo (HR = 0.39; P = .0726).
Looking at other outcomes, time to two-point clinical improvement was 7 days in the mavrilimumab arm and 11 days in the placebo arm, which Pupim noted was a non-significant difference. Similarly, time to room air was 7 days for the study drug and 9 days for placebo, which was also not significant.
The safety profile showed that no drug-related serious adverse events occurred in the mavrilimumab group, according to Pupim. “Secondary infections, which are known complications of COVID-19, occurred less frequently in mavrilimumab recipients compared to placebo,” she said. “Thrombotic events, another known complication of COVID-19, occurred in the placebo arm only.”
“In non-mechanically ventilated patients with severe COVID-19 pneumonia and hyperinflammation, mavrilimumab reduced mechanical ventilation and death” compared with placebo, Pupim concluded.
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