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|European Commission Approves Extended Indication For Amgen's Kyprolis® (Carfilzomib) For The Treatment Of Relapsed Multiple Myeloma Patients|
"In the Phase 3 head-to-head trial, Kyprolis in combination with dexamethasone doubled the time patients lived without their cancer progressing, as well as the rates of complete response compared to bortezomib and dexamethasone," said
The EC approved the extended indication for Kyprolis based on data from the Phase 3 head-to-head ENDEAVOR trial in which patients with multiple myeloma treated with Kyprolis plus dexamethasone (Kd) achieved superior progression-free survival (PFS) of 18.7 months compared to 9.4 months in those receiving bortezomib plus dexamethasone (Vd) (HR=0.53; 95 percent CI: 0.44, 0.65; p <0.0001). Kd also demonstrated improvement over Vd for secondary endpoints, including rates of complete response or better, which were double in patients treated with Kd compared to those treated with Vd (12.5 percent vs. 6.2 percent, p <0.0001). The tolerability profile was similar in the two arms, however patients treated with Kd experienced a significantly lower rate of grade 2 or higher neuropathy events than those treated with Vd, a frequent dose-limiting toxicity in patients receiving bortezomib (6 percent [95 percent CI: 4, 8] vs. 32 percent [95 percent CI: 28, 36], respectively). The most common adverse reactions that occurred in greater than 20 percent of patients treated with Kyprolis were anemia, fatigue, diarrhea, thrombocytopenia, nausea, pyrexia, dyspnea, respiratory tract infection, cough and peripheral edema.
Kyprolis was first approved by the EC in
Multiple myeloma is an incurable blood cancer, characterized by a recurring pattern of remission and relapse.1 It is a rare and very aggressive disease that accounts for approximately one percent of all cancers worldwide.2-4 In
The randomized ENDEAVOR (RandomizEd, OpeN Label, Phase 3 Study of Carfilzomib Plus DExamethAsone Vs Bortezomib Plus DexamethasOne in Patients With Relapsed Multiple Myeloma) trial of 929 patients evaluated Kyprolis in combination with low-dose dexamethasone, vs. bortezomib with low-dose dexamethasone in patients whose multiple myeloma has relapsed after at least one, but not more than three prior therapeutic regimens. The primary endpoint of the trial was PFS, defined as the time from treatment initiation to disease progression or death. In a clinical trial, measuring the PFS is one way to demonstrate how well a treatment works.6
As stated above, Kyprolis with dexamethasone (Kd) was superior to bortezomib and dexamethasone (Vd) and demonstrated significantly longer PFS. Improvement in PFS in the Kd arm compared to the Vd arm was seen across key pre-specified subgroups, including bortezomib-naive patients, those with high- or standard-risk cytogenetics and with or without prior transplantation.
In terms of secondary endpoints, Kd achieved a higher overall response rate than Vd (76.9 percent vs. 62.6 percent; p <0.0001). 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), 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.7 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 as were any-grade cardiac failure (grouped term; 8 percent vs. 3 percent) and acute renal failure (grouped term; 8 percent vs. 5 percent).7
Rates of grade 3 or higher adverse events were 73 percent in the Kyprolis group and 67 percent in the bortezomib group.7 Grade 3 or higher adverse events of interest in the Kyprolis and bortezomib groups included hypertension (preferred term; 9 percent vs. 3 percent), dyspnea (preferred term; 5 percent vs. 2 percent), cardiac failure (grouped term; 5 percent vs. 2 percent), acute renal failure (grouped term; 4 percent vs. 3 percent), ischemic heart disease (grouped term; 2 percent vs. 2 percent) and pulmonary hypertension (grouped term; 0.6 percent vs. 0.2 percent).7
Patients received treatment until progression with Kyprolis as a 30-minute infusion on days 1, 2, 8, 9, 15 and 16 of a 28 day treatment cycle. Patients received low-dose dexamethasone (20 mg) orally or intravenously on days 1, 2, 8, 9, 15, 16, 22, and 23 of each treatment cycle. For Cycle 1 only, Kyprolis was administered at 20 mg/m2 on days 1 and 2, and if tolerated 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)
Proteasomes play an important role in cell function and growth by breaking down proteins that are damaged or no longer needed.8 Kyprolis has been shown to block proteasomes, leading to an excessive build-up of proteins within cells.8 In some cells, Kyprolis can cause cell death, especially in myeloma cells because they are more likely to contain a higher amount of abnormal proteins.8,9
Kyprolis is approved in the U.S. for the following:
Kyprolis is also approved in
For more U.S. information, please visit www.kyprolis.com.
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
Acute Renal Failure
Tumor Lysis Syndrome
Hepatic Toxicity and Hepatic Failure
Posterior Reversible Encephalopathy Syndrome (PRES)
The most common adverse reactions occurring in at least 20% of patients treated with KYPROLIS in monotherapy trials: anemia, fatigue, thrombocytopenia, nausea, pyrexia, dyspnea, diarrhea, headache, cough, edema peripheral.
Full prescribing information for the U.S. is available at www.kyprolis.com.
Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology.
Amgen focuses on areas of high unmet medical need and leverages its expertise to strive for solutions that improve health outcomes and dramatically improve people's lives. A biotechnology pioneer since 1980, Amgen has grown to be one of the world's leading independent biotechnology companies, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential.
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The scientific information discussed in this news release relating to new indications for our products is preliminary and investigative and is not part of the labeling approved by the
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