Cubist Pharmaceuticals, Inc announced the early closing of enrolment in its ecallantide phase-2 programme. Ecallantide, in development as therapy to reduce bleeding in on-pump cardiac surgery, is now known as CB-500,929. After a regularly scheduled review meeting, the Data Safety Monitoring Board (DSMB) contacted the company to recommend a temporary suspension in enrolment in one of the CB-500,929 trials, Conserv-2. The Conserv-2 trial is evaluating a high dose of CB-500,929 (~75 mg total administered dose, which is the highest of three doses administered in the Conserv-1 dose ranging study) in higher-risk-of-bleed patients undergoing on- pump cardiac surgery.
The DSMB had observed a statistical difference in mortality between the arms of the Conserv-2 trial that it felt needed to be assessed before the trial could be resumed. While overall mortality was consistent with expected outcomes for the patient population in the Conserv-2 trial, the data for patients treated to date shows more deaths in the CB-500,929 arm. Initial review shows mortality observed in the trial was due to a variety of causes typically expected in a high-risk-for-bleed population undergoing cardiac surgery. There was no such imbalance detected in the Conserv-1 trial, also being monitored by the DSMB.
Cubist then determined that the best path forward, with more than 450 patients now enrolled in Conserv-1 and Conserv-2 combined, was to end enrolment, complete follow up of patients who have been treated, and move forward quickly toward data lock and a complete analysis of results. The original target enrollment for the Conserv-1 and Conserv-2 trials combined was 650. The company has notified the FDA of the DSMB recommendation and the company's decision to end enrolment early in both Conserv-1 and Conserv-2.
Cubist CEO Mike Bonney said, "When we designed phase-2 to study ecallantide as therapy to reduce blood loss in on pump cardiac surgery, we intentionally made it a robust program. The Conserv-2 trial in particular was intended to provide insight on all-cause outcomes in a higher risk cardiac surgery patient population. We will move as quickly as is prudent to analyze all the data from both Conserv- 1 and Conserv-2 in the first quarter."
Cubist Pharma is a biopharmaceutical company focused on the research, development, and commercialization of pharmaceutical products that address unmet medical needs in the acute care environment.