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|Amgen Submits Application In Europe To Expand Indication Of Kyprolis® (carfilzomib) For The Treatment Of Relapsed Multiple Myeloma|
The application is based on results from the Phase 3 head-to-head ENDEAVOR study in which patients with multiple myeloma treated with Kyprolis plus dexamethasone achieved superior progression-free survival (PFS) compared to those receiving Velcade® (bortezomib) plus dexamethasone (18.7 versus 9.4 months, respectively) (p<0.0001). The most common adverse events (greater than 25 percent) in the Kyprolis arm were diarrhea, anemia, fatigue, dyspnea, pyrexia and insomnia.
"Physicians need options to personalize treatment for complicated diseases like multiple myeloma," said
About Multiple Myeloma
The superiority of the Kyprolis combination compared to the bortezomib combination with respect to PFS was seen across key pre-specified subgroups, including bortezomib-naïve patients, those with high- or standard-risk cytogenetics and with or without prior transplantation. The Kyprolis combination also demonstrated superiority over the bortezomib combination for secondary endpoints, achieving a higher overall response rate (76.9 percent versus 62.6 percent; p<0.0001) and lower rate of grade 2 or higher neuropathy events (6 percent versus 32 percent; p<0.0001). Treatment with the Kyprolis combination resulted in a two-fold increase in the median duration of response (21.3 months) compared to the bortezomib combination (10.4 months).
In the Kyprolis and bortezomib groups, 54.3 percent and 28.6 percent of patients achieved a very good partial response or better (p<0.0001), and 12.5 percent and 6.2 percent of patients achieved a complete response or better (p<0.0001), respectively. Overall survival data are not yet mature and continue to be monitored.
Treatment discontinuation due to adverse events and on-study deaths were comparable between the two arms. A number of known adverse drug reactions were reported at a higher rate in the Kyprolis group compared with the bortezomib group, including any-grade dyspnea, hypertension, pyrexia, and cough (preferred terms) as were any-grade cardiac failure (grouped term; 8.2 percent versus 2.9 percent) and acute renal failure (grouped term; 8.2 percent versus 4.8 percent). The rates of cardiac and renal failure for Kyprolis were comparable to those observed in previous Phase 3 ASPIRE study.
Rates of grade 3 or higher adverse events were 73.2 percent in the Kyprolis group and 66.9 percent in the bortezomib group. Grade 3 or higher adverse events of interest in the Kyprolis and bortezomib groups included hypertension (preferred term; 8.9 percent versus 2.6 percent), dyspnea (preferred term; 5.4 percent versus 2.2 percent), cardiac failure (grouped term; 4.7 percent versus 1.8 percent), acute renal failure (grouped term; 4.0 percent versus 2.6 percent), ischemic heart disease (grouped term; 1.7 percent versus 1.6 percent) and pulmonary hypertension (grouped term; 0.6 percent versus 0.2 percent).
Patients received treatment until progression with Kyprolis as a 30-minute infusion on days 1, 2, 8, 9, 15 and 16 of 28 day treatment cycles, along with low-dose dexamethasone (20 mg). For Cycle 1 only, Kyprolis was administered at 20 mg/m2 on days 1 and 2, followed by escalation to 56 mg/m2 from day 8. Patients who tolerated 56 mg/m2 in Cycle 1 were kept at this dose for subsequent cycles. Patients who received bortezomib (1.3 mg/m2) with low-dose dexamethasone (20 mg) were administered bortezomib subcutaneously or intravenously at the discretion of the investigator and in accordance with regulatory approval of bortezomib. More than 75 percent of the patients in the control arm received bortezomib subcutaneously. This study was conducted at 235 sites worldwide. For information about this trial, please visit www.clinicaltrials.gov under trial identification number NCT01568866.
About Kyprolis® (carfilzomib)
Kyprolis is currently approved in
Kyprolis is approved in the U.S. in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received one to three prior lines of therapy.
Kyprolis is also indicated under
Kyprolis is a product of Onyx Pharmaceuticals, Inc. Onyx Pharmaceuticals is a subsidiary of Amgen and holds development and commercialization rights to Kyprolis globally, excluding Japan.
Important EU Product Safety Information
This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions.
Kyprolis treatment should be supervised by a physician experienced in the use of anti-cancer therapy. The most serious side effects that may occur during Kyprolis treatment include: Cardiac toxicity, pulmonary toxicities, pulmonary hypertension, dyspnea, hypertension including hypertensive crises, acute renal failure, tumor lysis syndrome, infusion reactions, thrombocytopenia, hepatic toxicity, posterior reversible encephalopathy syndrome (PRES) and thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS). The most common side effects are anemia, fatigue, diarrhea, thrombocytopenia, nausea, pyrexia, dyspnea, respiratory tract infection, cough and peripheral edema.
Please refer to the Summary of Product Characteristics for full European prescribing information.
Important U.S. Product Safety Information
Withhold Kyprolis for Grade 3 or 4 cardiac adverse events until recovery, and consider whether to restart Kyprolis based on a benefit/risk assessment.
Adequate hydration is required prior to each dose in Cycle 1. Monitor all patients for evidence of volume overload, especially patients at risk for cardiac failure. Adjust total fluid intake as clinically appropriate in patients with baseline cardiac failure or who are at risk for cardiac failure.
Patients > 75 years, the risk of cardiac failure is increased. Patients with New York Heart Association Class III and IV heart failure, recent myocardial infarction, and conduction abnormalities may be at greater risk for cardiac complications.
Acute Renal Failure
Tumor Lysis Syndrome
Hepatic Toxicity and Hepatic Failure
Thrombotic Thrombocytopenic Purpura /Hemolytic Uremic Syndrome (TTP/HUS)
Posterior Reversible Encephalopathy Syndrome (PRES)
Females of reproductive potential should be advised to avoid becoming pregnant while being treated with Kyprolis and the potential hazard to the fetus if Kyprolis is used during pregnancy.
The most common adverse events occurring in at least 20% of patients treated with Kyprolis in the combination therapy trial: decreased lymphocytes, decreased absolute neutrophil count, decreased phosphorus, anemia, neutropenia, decreased total white blood cell count, decreased platelets, diarrhea, fatigue, thrombocytopenia, pyrexia, muscle spasm, cough, upper respiratory tract infection, decreased hemoglobin, hypokalemia.
Full prescribing information for the U.S. is available at www.kyprolis.com.
Forward Looking Statements
No forward-looking statement can be guaranteed and actual results may differ materially from those we project. Discovery or identification of new product candidates or development of new indications for existing products cannot be guaranteed and movement from concept to product is uncertain; consequently, there can be no guarantee that any particular product candidate or development of a new indication for an existing product will be successful and become a commercial product. Further, preclinical results do not guarantee safe and effective performance of product candidates in humans. The complexity of the human body cannot be perfectly, or sometimes, even adequately modeled by computer or cell culture systems or animal models. The length of time that it takes for us and our partners to complete clinical trials and obtain regulatory approval for product marketing has in the past varied and we expect similar variability in the future. We develop product candidates internally and through licensing collaborations, partnerships and joint ventures. Product candidates that are derived from relationships may be subject to disputes between the parties or may prove to be not as effective or as safe as we may have believed at the time of entering into such relationship. Also, we or others could identify safety, side effects or manufacturing problems with our products after they are on the market. Our business may be impacted by government investigations, litigation and product liability claims. If we fail to meet the compliance obligations in the corporate integrity agreement between us and the U.S. government, we could become subject to significant sanctions. We depend on third parties for a significant portion of our manufacturing capacity for the supply of certain of our current and future products and limits on supply may constrain sales of certain of our current products and product candidate development.
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To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/amgen-submits-application-in-europe-to-expand-indication-of-kyprolis-carfilzomib-for-the-treatment-of-relapsed-multiple-myeloma-300188522.html