THOUSAND OAKS, Calif., Dec. 5, 2015 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today announced that The Lancet Oncology published results from the pivotal Phase 3 head-to-head ENDEAVOR study comparing Kyprolis® (carfilzomib) plus dexamethasone to Velcade® (bortezomib) plus dexamethasone in patients with relapsed multiple myeloma. The data showed that patients treated with Kyprolis plus dexamethasone achieved progression-free survival (PFS) of 18.7 months compared to 9.4 months in those receiving bortezomib plus dexamethasone (HR=0.53; 95 percent CI: 0.44,0.65 p<0.0001), a current standard of care in relapsed multiple myeloma.
These findings demonstrate that patients with relapsed multiple myeloma treated with Kyprolis lived twice as long without disease worsening as those treated with bortezomib. The most common adverse events (greater than 25 percent) in the Kyprolis arm were diarrhea, anemia, fatigue, dyspnea, pyrexia and insomnia. Treatment discontinuation due to adverse events and on-study deaths were comparable between the two arms.
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"In this head-to-head comparison, carfilzomib plus dexamethasone resulted in a twofold decrease in the risk of progression or death, compared with bortezomib plus dexamethasone, a result that was consistent regardless of age or prior bortezomib exposure," said study co-author and investigator, Meletios A. Dimopoulos, M.D., professor of Clinical Therapeutics at the National and Kapodistrian University of Athens, School of Medicine. "For patients with multiple myeloma, these results are clinically meaningful and translate to more than nine months without disease progression."
"Coupled with results previously seen in the ASPIRE pivotal trial, data from the ENDEAVOR study support the use of Kyprolis as a backbone therapy for the management of relapsed multiple myeloma, a difficult-to-treat blood cancer," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "This is an important publication because it provides clinical evidence of Kyprolis' potential to extend the time patients live without their disease progressing and improve the depth and duration of a response."
Multiple myeloma is an incurable blood cancer, characterized by a recurring pattern of remission and relapse, and while new therapies have become available, a significant unmet need still remains for patients no longer responding to treatment.1,2 Multiple myeloma is an orphan disease and accounts for approximately one percent of all cancers.3,4
Regulatory Status
Data from the ENDEAVOR study are the basis of the supplemental New Drug Application (sNDA) of Kyprolis in combination with dexamethasone for patients with relapsed multiple myeloma. The sNDA was accepted Sept.19, 2015, for priority review by the U.S. Food and Drug Administration (FDA) and the Prescription Drug User Fee Act (PDUFA) target action date is Jan. 22, 2016. Priority review is assigned to applications for drugs that treat serious conditions and would, if approved, provide significant improvements in the safety or effectiveness of the treatment, diagnosis or prevention of serious conditions. Amgen also just announced submission of the ENDEAVOR data to the European Commission for potential authorization of Kyprolis in combination with dexamethasone in the European Union.
About ENDEAVOR
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, versus 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.5
The superiority of the Kyprolis combination compared to the bortezomib combination with respect to PFS was seen across all pre-specified subgroups, including Velcade-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 vs. 62.6 percent; p<0.0001) and lower rate of grade 2 or higher neuropathy events (6 percent vs. 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 vs. 2.9 percent) and acute renal failure (grouped term; 8.2 percent vs. 4.8 percent). However, the rates of cardiac and renal failure for Kyprolis were comparable to those observed in the 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 vs. 2.6 percent), dyspnea (preferred term; 5.4 percent vs. 2.2 percent), cardiac failure (grouped term; 4.7 percent vs. 1.8 percent), acute renal failure (grouped term; 4.0 percent vs. 2.6 percent), ischemic heart disease (grouped term; 1.7 percent vs. 1.6 percent) and pulmonary hypertension (grouped term; 0.6 percent vs. 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.
Amgen Webcast Investor Meeting
Amgen will host a webcast investor meeting at the 57th Anuual American Society of Hematology (ASH) Meeting on Monday, Dec. 7, 2015, at 7 p.m. ET. Sean E. Harper, M.D., executive vice president of Research and Development at Amgen, along with members of Amgen's clinical development team and clinical investigators will participate to discuss data presented at ASH and Amgen's broader oncology portfolio of products.
Live audio of the conference call will be simultaneously broadcast over the Internet and will be available to members of the news media, investors and the general public.
The webcast, as with other selected presentations regarding developments in Amgen's business given by management at certain investor and medical conferences, can be found on Amgen's website, www.amgen.com, under Investors. Information regarding presentation times, webcast availability and webcast links are noted on Amgen's Investor Relations Events Calendar. The webcast will be archived and available for replay for at least 90 days after the event.
About Kyprolis® (carfilzomib) for Injection
Kyprolis is an irreversible proteasome inhibitor for use in the treatment of patients with relapsed multiple myeloma.2 Proteasomes play an important role in cell function and growth by breaking down proteins that are damaged or no longer needed.6 Kyprolis has been shown to block proteasomes, leading to an excessive build-up of proteins within cells.7 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.7 The irreversibility of Kyprolis' binding has also been shown to offer a more sustained inhibition of the targeted enzymes.8
Kyprolis is currently 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 FDA accelerated approval as a single agent for the treatment of patients with multiple myeloma who have received at least two prior therapies including bortezomib and an immunomodulatory agent and have demonstrated disease progression on or within 60 days of completion of the last therapy. Approval is based on response rate.
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