Candidate: Kevzara® (sarilumab)
Type: Interleukin-6 (IL-6) receptor antagonist approved by the FDA in 2017 to treat adults with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs.
Status: Regeneron Pharmaceuticals and Sanofi said July 2 their U.S.-based Phase III trial (NCT04315298) assessing Kevzara (400 mg dose) in COVID-19 patients requiring mechanical ventilation missed its primary and key secondary endpoints when added to best supportive care (placebo) compared to best supportive care alone. As a result, the companies stopped the trial, including in a second cohort of patients who received an 800 mg dose of Kevzara.
The companies said they saw “minor” positive trends in the primary pre-specified analysis group of 194 critically ill patients on Kevzara 400 mg who were mechanically ventilated at time of enrollment. Endpoints showing positive trends included the trial’s primary endpoint, the percentage of patients at day 22 who achieved at least a 1-point change from baseline on a 7-point scale ranging from death to discharge from hospital. Also trending positive was the proportion of patients who died by day 29; and proportion of patients who recovered by day 22.
However, those trends did not reach statistical significance and were countered by negative trends in a subgroup of critical patients who were not mechanically ventilated at baseline, Sanofi and Regeneron said.
In the primary analysis group, serious adverse events included multi-organ dysfunction syndrome (6% Kevzara, 5% placebo) and hypotension (4% Kevzara, 3% placebo). Adverse events were reported in 80% of Kevzara patients and 77% of placebo patients. The primary analysis group included 194 patients who were critically ill with COVID-19 and receiving mechanical ventilation at the time of enrolment. A second cohort, which was partially recruited and included just 27 patients, compared Kevzara 800 mg vs. placebo.
Detailed results will be submitted for publication in a peer-reviewed publication later this year, Sanofi and Regeneron said.
The Phase III trial, launched in March, was partially funded by the U.S. Biomedical Advanced Research and Development Authority (BARDA), under OT number: HHSO100201700020C. The study was designed to test whether Kevzara would perform as well as another interleukin-6 (IL-6) inhibitor, Roche (Genentech)’s Actemra®, did in a 21-patient, single-arm Chinese trial. The Chinese trial showed that inhibiting the IL-6 pathway allowed for successful hospital discharge in severe patients by rapidly reducing fever and improving oxygenation.
Still ongoing, the companies said, is a separate Phase III trial of Kevzara outside the U.S. in hospitalized patients with severe and critical COVID-19 using a different dosing regimen. Results from that trial are expected in the third quarter.
In April, Regeneron and Sanofi narrowed the Phase III portion of the Phase II/III trial to enroll only patients with critical respiratory illness caused by COVID-19, after preliminary analysis showed a benefit from the drug only in those patients. The companies have ended the portion of the study assessing the drug in less advanced “severe” respiratory illness caused by the disease. The Phase II portion assessed 457 hospitalized patients, who were categorized as “severe” (28% of patients), “critical” (49%) or “multi-system organ dysfunction” (MSOD; 23%).
The global clinical program has been launched in Italy, Spain, Germany, France, Canada, Russia and the U.S. Regeneron leads clinical studies in the U.S., while Sanofi does so overseas.
COVID-19: 200 Candidates and Counting
To navigate through the >200 potential therapeutic and vaccine options for COVID-19, GEN has grouped the candidates into four broad categories based on their developmental and (where applicable) clinical progress:
● FRONT RUNNER – the most promising therapeutics/vaccines based on clinical progress, favorable data or both.
● DEFINITELY MAYBE – earlier phases with promising partners, or more advanced candidates in development that have generated uneven data
● KEEPING AN EYE ON… – interesting technology, attracting notable partners, or both, but preliminary data.
● TOO SOON TO TELL – longshots pending additional experimental and/or clinical data.
GEN has also tagged the most common treatment types: