Mavrilimumab Reduces Progression to Mechanical Ventilation, Improves Survival in Severe COVID-19 Pneumonia and Hyperinflammation

A single infusion of mavrilimumab may reduce progression to mechanical ventilation and improve survival in patients with severe COVID-19 pneumonia and hyperinflammation receiving supplemental oxygen therapy, corticosteroids, and remdesivir, according to study findings presented at the European Alliance of Associations for Rheumatology (EULAR) 2021 Virtual Congress, held from June 2 to 5, 2021.

In an ongoing, global, randomized, double-blind, placebo-controlled phase 2/3 trial, researchers aimed to determine the safety and efficacy of mavrilimumab in adults hospitalized with severe COVID-19 pneumonia and systemic hyperinflammation.

In phase 2 of the trial, participants requiring supplemental oxygen therapy without mechanical ventilation were assigned to cohort 1 and patients requiring mechanical ventilation for more than 48 hours before randomization were assigned to cohort 2. A total of 116 patients (mean age, 57 years; non-White, 43%; BMI ≥30) who were assigned to cohort 1 were randomly assigned (1:1:1) to receive either a single dose of intravenously administered mavrilimumab (6 or 10 mg/kg) or placebo.

The primary efficacy outcome was the number of living patients who did not require mechanical ventilation after day 29 of the analysis. Secondary outcomes included the time to 2-point clinical improvement as measured using the National Institute of Allergy and Infectious Diseases COVID-19 ordinal scale; the time to return to room air; and mortality through day 29. Of note, the researchers prespecified the evidentiary standard of a 2-sided α to be 0.2, which was not adjusted for multiplicity.

All patients received local standard of care; 96% of patients received treatment with corticosteroids, including dexamethasone, and 29% received treatment with remdesivir. Among patients who received mavrilimumab, there was no significant differences in outcomes between 6 mg/kg and 10 mg/kg doses and results for these arms were presented together.

At day 29, patients who received mavrilimumab had a reduced need for mechanical ventilation and had improved survival. Compared with patients who received placebo, the number of patients who received mavrilimumab who were alive and free of mechanical ventilation was 12.3 percentage points greater (P =.1224); mortality at day 29 was 12.5 percentage points lower (P =.0718).

Among patients who received treatment with mavrilimumab, the risk for mechanical ventilation or death through day 29 was reduced by 65% (hazard ratio [HR], 0.35; P =.0175) and risk for death through day 29 was reduced by 61% (HR, 0.39; P =.0726).

Adverse events, including secondary infections and thrombotic events, were less frequently observed in patients who received mavrilimumab, and thrombotic events only occurred in patients in the placebo cohort (12.5%).

“Results indicate mavrilimumab, a potent inhibitor of [granulocyte/macrophage-colony stimulating factor] signaling, may have added clinical benefit on top of the current standard therapy for COVID-19,” the researchers reported. “Of potential importance is that this treatment strategy is mechanistically independent of the specific virus or viral variant.”

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.

Reference

Pupim L, Wang TS, Hudock K, et al. Mavrilimumab improves outcomes in phase 2 trial in non-mechanically-ventilated patients with severe COVID-19 pneumonia and systemic hyperinflammation. Presented at: EULAR 2021 Virtual Congress; June 2-5, 2021. Abstract LB0001.