Among a spate of COVID-19-related therapy developments to start the week, Kiniksa Pharmaceuticals Inc. produced positive phase II data of its monoclonal antibody, mavrilimumab, in treating non-mechanically ventilated patients with severe COVID-19 pneumonia and hyperinflammation.
The positive data confirmed the company’s approach and will allow it to finalize the phase III study design, John Paolini, Kiniksa’s chief medical officer, told BioWorld. That phase III’s enrollment is ongoing.
The study’s primary endpoint was the proportion of patients who survive and are free of mechanical ventilation at day 29, which was 12.3% higher with mavrilimumab vs. placebo (p=0.1224, meeting the predefined statistical threshold of p<0.2). In a non-mechanically ventilated cohort, 1,116 patients with hypoxia and severe COVID-19 pneumonia/hyperinflammation were enrolled across sites in the U.S., Brazil, Chile, Peru, and South Africa and randomized in a 1-to-1-to-1 ratio to receive a single I.V.-delivered dose of mavrilimumab 10 mg/kg, 6 mg/kg or placebo. Key secondary endpoints included time to two-point clinical improvement on the National Institute of Allergy and Infectious Diseases scale, time to return to room air and mortality.There was also a 65% reduction in risk of mechanical ventilation/death with mavrilimumab vs. placebo (p=0.0175) and a 61% reduction in risk of death with mavrilimumab vs. placebo (p=0.0726).
The study’s baseline population was 43% non-white, 49% were obese (with a body mass index greater than or equal to 30) and 29% were older than 65.
The data also showed a clinical improvement on top of steroids and/or antivirals.
Mavrilimumab is a fully human, anti-CD3 monoclonal antibody targeting granulocyte macrophage colony-stimulating factor receptor alpha.
Shares of Kiniksa (NASDAQ:KNSA) closed April 12 at $16.15, down $1.54.
REGEN-COV protects from infection
Regeneron Pharmaceuticals Inc. also posted positive data from its two phase III trials of REGEN-COV (casirivimab with imdevimab) for treating COVID-19. The study 2069B showed recently infected asymptomatic patients receiving 1,200 mg subcutaneously reduced the overall risk of progressing to symptomatic COVID-19 by 31%, which was the primary endpoint, and 76% by day three.
Data from the Tarrytown, N.Y.-based company’s other phase III study, 2069A, showed that REGEN-COV protected household contacts from exposure to SARS-CoV-2 at home, with 72% protection against symptomatic infections in the first week and 93% in subsequent weeks. The trial met its primary and key secondary endpoints. Both studies were conducted with the National Institute of Allergy and Infectious Disease, part of the U.S. NIH.
Shares of Regeneron (NASDAQ:REGN) closed April 12 at $472.80, down $2.37.
Oxford University also posted positive interim phase III data from its study of inhaled budesonide showing the corticosteroid shortened the recovery time of COVID-19 patients older than age 50 by a median of three days. The analysis also showed that among patients who completed all 28 days of study follow-up, 8.5% in the budesonide group were hospitalized with COVID-19 compared with 10.3% in the usual care group.
Farxiga misses in phase III
Astrazeneca plc’s phase III study did not fare so well. High-level results from the primary analysis of the DARE-19 study assessing hospitalized COVID-19 patients treated with Farxiga (dapagliflozin) did not demonstrate statistical significance in its primary endpoint of prevention in measuring organ dysfunction and all-cause mortality nor in the primary endpoint of recovery measuring a change in clinical status (from early recovery to death) at 30 days.
The clinical trial was evaluating the sodium-glucose co-transporter-2 (SGLT2) inhibitor in patients hospitalized with COVID-19 with risk factors for developing serious complications, including hypertension, type 2 diabetes, atherosclerotic cardiovascular disease, heart failure or chronic kidney diseases in stages 3-4.