Benzinga | Dec 22, 2020 08:03AM EST

Kiniksa Announces Data From US Investigator-Initiated Study Of Mavrilimumab In Severe COVID-19 Pneumonia And Hyperinflammation

- Early signal of efficacy with trends toward lower mortality and shorter duration of mechanical ventilation in patients treated with mavrilimumab --



- Data from the Phase 2 portion of Kiniksa's adaptive design Phase 2/3 clinical trial expected in 1H 2021 -

HAMILTON, Bermuda, Dec. 22, 2020 (GLOBE NEWSWIRE) -- Kiniksa Pharmaceuticals, Ltd. (NASDAQ:KNSA) ("Kiniksa"), a biopharmaceutical company with a pipeline of assets designed to modulate immunological pathways across a spectrum of diseases, today announced data from the investigator-initiated placebo-controlled study of mavrilimumab in patients with severe COVID-19 pneumonia and hyperinflammation. Enrollment in the study was closed early to focus on Kiniksa's registrational development program in the same patient population.

"The data showed encouraging trends of reduced mortality and duration of mechanical ventilation in patients treated with mavrilimumab, especially when considering that many patients in this placebo-controlled study had already been treated with remdesivir and/or corticosteroids," said John F. Paolini, MD, PhD, Chief Medical Officer of Kiniksa. "These data are comparable to the data from the open-label treatment protocol reported in June of 2020. We believe the totality of these two data sets supports continued evaluation of mavrilimumab in severe COVID-19 pneumonia and hyperinflammation."

The investigator-initiated study was a randomized, double-blind, placebo-controlled study across a consortium of U.S. academic sites, including Cleveland Clinic, University of Cincinnati, and Virginia Commonwealth University, designed to evaluate the efficacy and safety of mavrilimumab versus placebo on top of standard of care therapy in patients with severe COVID-19 pneumonia and hyperinflammation. The study enrolled 40 patients with severe COVID-19 pneumonia (all patients presented with pneumonia and hypoxia: all patients required supplemental oxygen, 50% of patients required non-invasive ventilation, none required mechanical ventilation at baseline; median PaO2/FiO2 ratio 137) and hyperinflammation (median C-reactive protein 13.1 mg/dL). Concomitant medications at baseline included corticosteroids (65% of patients) and remdesivir (75% of patients). Patients were randomized 1:1 to a single intravenous (IV) infusion of mavrilimumab 6mg/kg (n=21) or placebo (n=19) and were followed for at least 60 days.

Data showed an early signal of efficacy, with trends toward clinical improvement as well as lower mortality and shorter duration of mechanical ventilation in patients treated with mavrilimumab on top of corticosteroids, including dexamethasone, and/or remdesivir.

* There was a 20.5% relative increase in the primary efficacy endpoint, the proportion of patients alive and off supplemental oxygen at Day 14 (mavrilimumab: 57.1% [n=21]; placebo: 47.4% [n=19]; nominal p=0.536).

* There was a 20.7% relative increase in the secondary efficacy endpoint, the proportion of patients alive and without respiratory failure at Day 28 (mavrilimumab: 95.2%; placebo: 78.9%; nominal p=0.172).

* There was 1 death (4.8%) in the mavrilimumab arm by Day 28, compared to 3 deaths (15.8%) in the placebo arm (nominal p=0.222). By Day 60 there was 1 death (4.8%) in the mavrilimumab arm, compared to 4 deaths (21.1%) in the placebo arm (nominal p=0.108).

* While the percentage of patients who progressed to mechanical ventilation was similar between treatment arms (mavrilimumab: 23.8% [n=5]; placebo: 21.1% [n=4]), the median (interquartile) duration of mechanical ventilation was shorter in the mavrilimumab arm (12 [9.0, 18.0] days) compared to the placebo arm (17 [11.0, 24.5] days). Additionally, 4 of the 5 patients who progressed to mechanical ventilation in the mavrilimumab arm had recovered by Day 28, whereas all patients in the placebo arm who progressed to mechanical ventilation had died by Day 28.

* There was no difference in serious adverse events between the mavrilimumab arm and the placebo arm.

"In the context of the evolving standard of care, the data from this trial in severe COVID-19 pneumonia and hyperinflammation are encouraging," said Sanj K. Patel, Chief Executive Officer and Chairman of the Board of Kiniksa. "While vaccination is expected to be the mainstay of COVID-19 prevention, we believe there will remain an unmet need for effective therapeutics to treat patients who develop severe hyperinflammation. I look forward to the results of the larger Kiniksa-sponsored trial of mavrilimumab in this patient population."

Kiniksa is enrolling the Phase 2 portion of an adaptive design, placebo-controlled Phase 2/3 clinical trial in severe COVID-19 pneumonia and hyperinflammation. The company expects data from the Phase 2 portion of the trial in the first half of 2021.