Study details and other outcome results
The study presented by Dr. Pupim was a phase 2/3 double-blind, placebo-controlled trial predominantly conducted in Brazil, the United States, and South Africa, with some participation in Peru and Chile.
Patients were eligible for inclusion if they had had a positive COVID-19 test within 14 days of randomization and had been hospitalized but not ventilated. Evidence of bilateral pneumonia on chest x-ray or CT scan and clinical laboratory evidence indicative of hyperinflammation were also prerequisites for study enrollment.
The ongoing study comprised two cohorts, Dr. Pupim explained: patients who have not been ventilated and those who have recently been ventilated. Dr. Pupim presented the data on the nonventilated cohort, noting that there was a total of 116 patients aged a mean of 57 years.
Patients were randomized to one of three treatment arms: two groups received a single intravenous infusion of mavrilimumab, either 6 mg/kg or 10 mg/kg, and the third group got a placebo.
“Using a time-to-event approach, looking at mechanical ventilation-free survival, mavrilimumab recipients experienced a 65% reduction in the risk of mechanical ventilation or death,” Dr. Pupim said (P = .0175).
“Separation in the Kaplan-Meier curves was evident very early after study drug administration,” she added.
There were trends toward a faster benefit with mavrilimumab than placebo in two other key secondary endpoints: the median time to achieving a two-point clinical improvement (7 vs. 11 days) and the median time to room air (7 vs. 9 days).
Timing of mavrilimumab administration and safety
Study coauthor and chief clinical development officer at Kiniksa, Arian Pano, MD, answered questions on the presentation. When asked about the timing of giving mavrilimumab, he said: “Based on these data it is before they go to ventilation, as soon as you have symptoms of hyperinflammation and a need for oxygen.”
Mavrilimumab is given as a single infusion “and has been well tolerated; virtually no interruptions occurred in this study.”
No serious adverse events related to mavrilimumab were seen, and adverse events, including secondary infections, which are known complications of COVID-19, occurred less frequently in mavrilimumab recipients, compared with placebo.
Dr. Pupim reported that there was a case of tuberculosis in one patient treated with mavrilimumab (10 mg/kg). That case had occurred in an “endemic area for tuberculosis,” and the patient had been screened before entry but only via a sputum sample.
“Prior to these events, the patient received high-dose corticosteroids, a known risk factor for reactivation of TB, and thus the potential additive contribution of mavrilimumab, if any, is uncertain.” Dr. Pupim said.
“Thrombotic events, another known complication of COVID-19, occurred in the placebo arm only,” she added.
Dr. Pano commented that the study has now “seamlessly continued to phase 3. So, basically, we did not stop the study. At the end of phase 2, we just locked the database and collected the data.” Both the 6 mg/kg and 10 mg/kg are being studied, but it’s “very likely [that] 6 mg/kg could be the dose that we may bring forward to the clinic in terms of registration, but that’s at this point in time. We will need to wait for the phase 3 data,” he observed. Those findings will hopefully be available later this year.
Kiniksa funded the study. Dr. Pupim, Dr. Pano, and multiple study coinvestigators are employees of the company.
Dr. Schulze-Koops was not involved in the study and had no specific disclosures. Dr. Conway had no financial disclosures to make in relation to his comments.