|Systematic (IUPAC) name|
|Licence data||US FDA:|
|Pregnancy cat.||D (US)|
|Legal status||℞-only (US)|
|Mol. mass||719.91 g mol|
The US FDA approved it for relapsed and refractory multiple myeloma on 20 July 2012.
Discovery, early development and regulatory approval 
Carfilzomib is derived from epoxomicin, a natural product that was shown by the laboratory of Craig Crews at Yale University to inhibit the proteasome. The Crews laboratory subsequently invented a more specific derivative of epoxomicin named YU101, which was licensed to Proteolix, Inc.. Scientists at Proteolix modified YU101 to create carfilzomib, which they advanced to multiple Phase 1 and 2 clinical trials, including a pivotal Phase 2 clinical trial designed to seek accelerated approval. Clinical trials for carfilzomib continue under Onyx Pharmaceuticals, which acquired Proteolix in 2009.
In January 2011, the U.S. FDA granted carfilzomib fast-track status, allowing Onyx to initiate a rolling submission of its new drug application for carfilzomib. In December 2011, the FDA granted Onyx standard review designation,  for its new drug application submission based on the 003-A1 study, an open-label, single-arm Phase 2b 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.
Carfilzomib was approved by the FDA for use in patients with relapsed and refractory multiple myeloma on 20 July 2012. Onyx expects to launch the drug in the U.S. on 1 August 2012. When it launches, it will cost $10,000 per 28-day cycle, making it the most expensive FDA-approved drug for multiple myeloma.
Carfilzomib irreversibly binds to and inhibits the chymotrypsin-like activity of the 20S proteasome, an enzyme that degrades unwanted cellular proteins. Inhibition of proteasome-mediated proteolysis results in a build-up of polyubiquinated proteins, which may cause cell cycle arrest, apoptosis, and inhibition of tumor growth.
Clinical trials 
A single-arm, phase 2 trial (-003-A1) of carfilzomib in patients with relapsed and refractory multiple myeloma showed that single-agent carfilzomib had durable responses in 36 percent of the 257 patients evaluated.
In another phase 2 trial (-006) of patients with relapsed and/or refractory multiple myeloma, carfilzomib in combination with lenalidomide and dexamethasone demonstrated an overall response rate of 78 percent. Researchers found carfilzomib could be administered over a period of 14–23 months with no new or overlapping toxicities.
In a phase 2 trial (-004), carfilzomib had a 53 percent overall response rate among patients with relapsed and/or refractory multiple myeloma who had not previously received bortezomib. This study also found prolonged carfilzomib treatment is well-tolerated with approximately 22 percent of patients continuing treatment beyond one year.
In a frontline phase 1/2 study, the combination of carfilzomib, lenalidomide, and low-dose dexamethasone was highly active and well tolerated, permitting the use of full doses for an extended time in newly-diagnosed multiple myeloma patients, with limited need for dose modification. Responses were rapid and improved over time, reaching 100% very good partial response.
A phase 3 trial comparing carfilzomib, lenalidomide and dexamethasone versus lenalidomide and dexamethasone in patients with relapsed multiple myeloma is ongoing. It is no longer recruiting and should report in 2014.
- Carfilzomib, NCI Drug Dictionary
- Meng, L; Mohan, R., Kwok, B.H., Elofsson, M., Sin, N., Crews, C.M. (1999). "Epoxomicin, a potent and selective proteasome inhibitor, exhibits in vivo antiinflammatory activity". Proc Natl Acad Sci USA 96 (18): 10403–8. doi:10.1073/pnas.96.18.10403. PMC 17900. PMID 10468620.
- Myung, J; Kim, K.B., Lindsten, K., Dantuma, N.P., Crews, C.M. (2001). "Lack of proteasome active site allostery as revealed by subunit-specific inhibitors". Mol Cell 7 (2): 411–20. doi:10.1016/S1097-2765(01)00188-5. PMID 11239469.
- Carfilzomib: From Discovery To Drug
- "Onyx multiple myeloma drug wins FDA fast-track status". San Francisco Business Times. 2011-01-31. Retrieved 2011-09-01.
- "Beacon Breaking News – Carfilzomib to Get Standard, Not Priority, FDA Review". The Myeloma Beacon. Retrieved 2012-02-27.
- "Fast Track, Accelerated Approval and Priority Review; Accelerating Availability of New Drugs for Patients with Serious Diseases". FDA. Retrieved 2012-02-27.
- "PX-171-003-A1, an open-label, single-arm, phase (Ph) II study of carfilzomib (CFZ) in patients (pts) with relapsed and refractory multiple myeloma (R/R MM): Long-term follow-up and subgroup analysis". ASCO 2011; Abstract 8027. 2011. Retrieved 2011-09-01.
- "FDA approves Kyprolis for some patients with multiple myeloma". U.S. Food and Drug Administration.
- "FDA Approves Kyprolis (Carfilzomib) For Relapsed And Refractory Multiple Myeloma". The Myeloma Beacon. Retrieved 2012-07-20.
- Onyx Says Carfilzomib Results Promising, Drug Discovery & Development, July 27, 2010
- "Phase II results of Study PX-171-007: A phase Ib/II study of carfilzomib (CFZ), a selective proteasome inhibitor, in patients with selected advanced metastatic solid tumors" - ASCO 2009; Abstract 3515.
- "ASCO Showcasing Bay Area Cancer Therapies". San Francisco Business Times. 2011-06-02. Retrieved 2011-09-01.
- "Interim results from PX-171-006, a phase (Ph) II multicenter dose-expansion study of carfilzomib (CFZ), lenalidomide (LEN), and low-dose dexamethasone (loDex) in relapsed and/or refractory multiple myeloma (R/R MM)". ASCO 2011; Abstract 8025. 2011. Retrieved 2011-09-01.
- "The effect of carfilzomib (CFZ) in patients (Pts) with bortezomib (BTZ)-naive relapsed or refractory multiple myeloma (MM): Updated results from the PX-171-004 study". ASCO 2011; Abstract 8026. 2011. Retrieved 2011-09-01.
- "Siegel DS, Martin T, Wang, M, et al. Results of PX-171- 003-A1, an open-label, single-arm, phase 2 study of carfilzomib in patients with relapsed and refractory multiple myeloma. Presented at: 52nd ASH Annual Meeting and Exposition; December 4-7, 2010; Orlando, Florida.". OncLive.com. 2011-03-09. Retrieved 2011-09-01.
- "Final Results of a Frontline Phase 1/2 Study of Carfilzomib Lenalidomide, and Low-Dose Dexamethasone (CRd) in Multiple Myeloma (MM)". ASH 20111; Abstract 631. Retrieved 2012-02-27.
- "Phase 3 Study Comparing Carfilzomib, Lenalidomide, and Dexamethasone (CRd) Versus Lenalidomide and Dexamethasone (Rd) in Subjects With Relapsed Multiple Myeloma". ClinicalTrials.gov. 2011-08-04. Retrieved 2011-09-01.