[4] Carfilzomib is derived from epoxomicin, a natural product that was shown by the laboratory of Craig Crews at Yale University to inhibit the proteasome.

[11] In December 2011, the FDA granted Onyx standard review designation,[12][13] for its new drug application submission based on the 003-A1 study, an open-label, single-arm phase IIb trial.

The trial evaluated 266 heavily-pretreated patients with relapsed and refractory multiple myeloma who had received at least two prior therapies, including bortezomib and either thalidomide or lenalidomide.

[3] In a phase II trial (004), carfilzomib had a 53% overall response rate among patients with relapsed and/or refractory multiple myeloma who had not previously received bortezomib.

[18] In another phase II trial (006) of patients with relapsed and/or refractory multiple myeloma, carfilzomib in combination with lenalidomide and dexamethasone demonstrated an overall response rate of 69%.

[20][21] In phase II trials of carfilzomib, the most common grade 3 or higher treatment-emergent adverse events were hematologic toxicity [22] with thrombocytopenia, anemia, lymphopenia, neutropenia, pneumonia, fatigue and hyponatremia.

Treatment discontinuation because of adverse effects occurred less frequently in the KRd arm, and events included thrombocytopenia, hypertension, and heart failure.