What it is
Carfilzomib is a chain of four amino-acid units with a reactive trap at one end. The Kyprolis label calls it "a tetrapeptide epoxyketone." Read from its chemical name, the chain is a morpholinoacetyl cap, then homophenylalanine (phenylalanine with one extra carbon — not one of the 20 standard amino acids), leucine, phenylalanine, and a final leucine whose end is an epoxyketone, a strained three-membered ring next to a ketone (our reading). Formula C40H57N5O7, molecular weight 719.9.
It is "practically insoluble in water", so every vial carries fifty times its weight in a cyclodextrin solubiliser — 500 mg of sulfobutylether beta-cyclodextrin per 10 mg of carfilzomib (label).
How it works
Like bortezomib, carfilzomib blocks the proteasome, the protein-disposal complex cells rely on to clear tagged proteins. The difference is the grip. The label states that carfilzomib "irreversibly binds to the N-terminal threonine-containing active sites of the 20S proteasome", the cutting core inside the larger 26S complex: the epoxyketone reacts with the active site and stays bound, where bortezomib's boronic acid lets go. In laboratory studies it was antiproliferative and pro-apoptotic in tumour cells (label).
What the label's trials show
| Regimen (label indication) | Trial | Result |
|---|---|---|
| With lenalidomide + dexamethasone, 1–3 prior lines | ASPIRE (NCT01080391), 792 patients, vs lenalidomide + dexamethasone, open-label | Progression-free survival 26.3 vs 17.6 months (HR 0.69); overall survival 48.3 vs 40.4 months (HR 0.79); response 87% vs 67% |
| With dexamethasone, 1–3 prior lines | ENDEAVOR (NCT01568866), 929 patients, vs bortezomib + dexamethasone, open-label | Progression-free survival 18.7 vs 9.4 months (HR 0.53); overall survival 47.6 vs 40.0 months (HR 0.79); response 77% vs 63% |
Both trials were open-label. ASPIRE excluded patients with creatinine clearance below 50 mL/min, NYHA class III–IV heart failure or a heart attack in the previous four months — groups the warnings below are about. ENDEAVOR is a trial result the label reports, not a ranking by this library. The label also lists approvals with daratumumab or isatuximab and as a single agent.
Safety
The first warning on the label is cardiac toxicity: new or worsening heart failure, cardiomyopathy, myocardial ischaemia and infarction, "including fatalities", some in patients with normal heart function at baseline, and "death due to cardiac arrest has occurred within one day" of a dose. In the randomised combination trials, cardiac failure events occurred in 8% and arrhythmias in 8%. Further warnings: acute kidney failure, tumour lysis syndrome, lung toxicity including acute respiratory distress, pulmonary hypertension, shortness of breath and hypertension including hypertensive crisis. Doses, set by body surface area, are on the label and decided by the treating team.
Where it stands
- Approved in the US since 2012-07-20 (Kyprolis, NDA 202714, Onyx Pharmaceuticals, an Amgen company), in 10, 30 and 60 mg vials.
- No generic listed in Drugs@FDA (openFDA, 2026-10-14).
- Research record: PubMed indexes 1,941 records, 75 tagged as randomised trials (2026-10-14).
Related reading
The first proteasome blocker, a two-unit peptide, is bortezomib. For the bond that joins carfilzomib's four units, see the peptide bond; for the standard building blocks it partly departs from, the amino acid chart.