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Photo courtesy of Amgen
The European Commission (EC) has granted marketing authorization for carfilzomib (Kyprolis) to be used in combination with lenalidomide and dexamethasone to treat adults with multiple myeloma (MM) who have received at least 1 prior therapy.
Carfilzomib is the first irreversible proteasome inhibitor approved in the European Union (EU) as part of combination treatment for patients with relapsed MM.
Carfilzomib was granted orphan designation in the EU in 2008. The drug also received accelerated assessment, which shortened the review period from 210 days to 150 days.
Carfilzomib is a product of Onyx Pharmaceuticals, Inc., a subsidiary of Amgen that holds development and commercialization rights to the drug globally, excluding Japan.
ASPIRE trial
The EC approved carfilzomib based on data from the phase 3 ASPIRE trial, which were presented at ASH 2014 and published in NEJM.
The trial enrolled 792 patients with relapsed or refractory MM who had received 1 to 3 prior lines of therapy. The patients were randomized (1:1) to receive carfilzomib plus lenalidomide and dexamethasone (KRd) or just lenalidomide and dexamethasone (Rd) for 18 cycles.
Lenalidomide and dexamethasone were continued thereafter until disease progression. There was no planned cross-over from the control arm to treatment with carfilzomib.
The study’s primary endpoint was progression-free survival. The median progression-free survival was significantly longer in the KRd arm than the Rd arm—26.3 months and 17.6 months, respectively (hazard ratio=0.69, P=0.0001).
At the time of analysis, the difference in overall survival did not reach the prespecified boundary for statistical significance.
The overall response rate was 87% in the KRd arm and 67% in the Rd arm. The median duration of response was 28.6 months and 21.2 months, respectively.
The rates of death due to adverse events (AEs) within 30 days of the last dose were similar between the treatment arms.
The most common causes of death not due to progressive disease occurring in patients in the KRd arm and the Rd arm, respectively, were cardiac disorders (3% vs 2%), infection (2% vs 3%), renal events (0% vs less than 1%), and other AEs (2% vs 3%).
Serious AEs were reported in 60% of patients in the KRd arm and 54% in the Rd arm. The most common serious AEs reported in the KRd arm and the Rd arm, respectively, were pneumonia (14% vs 11%), respiratory tract infection (4% vs 2%), pyrexia (4% vs 2%), and pulmonary embolism (3% vs 2%).
Global development
In the US, carfilzomib is approved for use in combination with lenalidomide and dexamethasone to treat MM patients who have received 1 to 3 prior lines of therapy.
Carfilzomib also has accelerated approval in the US as a single agent to treat MM patients who have received at least 2 prior therapies, including bortezomib and an immunomodulatory agent, and have demonstrated disease progression on or within 60 days of the completion of last therapy.
Amgen plans to submit data from the phase 3 ENDEAVOR trial for potential authorization of carfilzomib in combination with dexamethasone in the EU.
This data serves as the basis of the supplemental new drug application of carfilzomib in combination with dexamethasone for patients with relapsed MM, which has been accepted for priority review in the US.
In addition to the US and EU, carfilzomib is approved for use in Argentina, Israel, Kuwait, Mexico, Thailand, and Colombia. Additional regulatory applications for the drug have been submitted to health authorities worldwide. 
Photo courtesy of Amgen
The European Commission (EC) has granted marketing authorization for carfilzomib (Kyprolis) to be used in combination with lenalidomide and dexamethasone to treat adults with multiple myeloma (MM) who have received at least 1 prior therapy.
Carfilzomib is the first irreversible proteasome inhibitor approved in the European Union (EU) as part of combination treatment for patients with relapsed MM.
Carfilzomib was granted orphan designation in the EU in 2008. The drug also received accelerated assessment, which shortened the review period from 210 days to 150 days.
Carfilzomib is a product of Onyx Pharmaceuticals, Inc., a subsidiary of Amgen that holds development and commercialization rights to the drug globally, excluding Japan.
ASPIRE trial
The EC approved carfilzomib based on data from the phase 3 ASPIRE trial, which were presented at ASH 2014 and published in NEJM.
The trial enrolled 792 patients with relapsed or refractory MM who had received 1 to 3 prior lines of therapy. The patients were randomized (1:1) to receive carfilzomib plus lenalidomide and dexamethasone (KRd) or just lenalidomide and dexamethasone (Rd) for 18 cycles.
Lenalidomide and dexamethasone were continued thereafter until disease progression. There was no planned cross-over from the control arm to treatment with carfilzomib.
The study’s primary endpoint was progression-free survival. The median progression-free survival was significantly longer in the KRd arm than the Rd arm—26.3 months and 17.6 months, respectively (hazard ratio=0.69, P=0.0001).
At the time of analysis, the difference in overall survival did not reach the prespecified boundary for statistical significance.
The overall response rate was 87% in the KRd arm and 67% in the Rd arm. The median duration of response was 28.6 months and 21.2 months, respectively.
The rates of death due to adverse events (AEs) within 30 days of the last dose were similar between the treatment arms.
The most common causes of death not due to progressive disease occurring in patients in the KRd arm and the Rd arm, respectively, were cardiac disorders (3% vs 2%), infection (2% vs 3%), renal events (0% vs less than 1%), and other AEs (2% vs 3%).
Serious AEs were reported in 60% of patients in the KRd arm and 54% in the Rd arm. The most common serious AEs reported in the KRd arm and the Rd arm, respectively, were pneumonia (14% vs 11%), respiratory tract infection (4% vs 2%), pyrexia (4% vs 2%), and pulmonary embolism (3% vs 2%).
Global development
In the US, carfilzomib is approved for use in combination with lenalidomide and dexamethasone to treat MM patients who have received 1 to 3 prior lines of therapy.
Carfilzomib also has accelerated approval in the US as a single agent to treat MM patients who have received at least 2 prior therapies, including bortezomib and an immunomodulatory agent, and have demonstrated disease progression on or within 60 days of the completion of last therapy.
Amgen plans to submit data from the phase 3 ENDEAVOR trial for potential authorization of carfilzomib in combination with dexamethasone in the EU.
This data serves as the basis of the supplemental new drug application of carfilzomib in combination with dexamethasone for patients with relapsed MM, which has been accepted for priority review in the US.
In addition to the US and EU, carfilzomib is approved for use in Argentina, Israel, Kuwait, Mexico, Thailand, and Colombia. Additional regulatory applications for the drug have been submitted to health authorities worldwide.
Photo courtesy of Amgen
The European Commission (EC) has granted marketing authorization for carfilzomib (Kyprolis) to be used in combination with lenalidomide and dexamethasone to treat adults with multiple myeloma (MM) who have received at least 1 prior therapy.
Carfilzomib is the first irreversible proteasome inhibitor approved in the European Union (EU) as part of combination treatment for patients with relapsed MM.
Carfilzomib was granted orphan designation in the EU in 2008. The drug also received accelerated assessment, which shortened the review period from 210 days to 150 days.
Carfilzomib is a product of Onyx Pharmaceuticals, Inc., a subsidiary of Amgen that holds development and commercialization rights to the drug globally, excluding Japan.
ASPIRE trial
The EC approved carfilzomib based on data from the phase 3 ASPIRE trial, which were presented at ASH 2014 and published in NEJM.
The trial enrolled 792 patients with relapsed or refractory MM who had received 1 to 3 prior lines of therapy. The patients were randomized (1:1) to receive carfilzomib plus lenalidomide and dexamethasone (KRd) or just lenalidomide and dexamethasone (Rd) for 18 cycles.
Lenalidomide and dexamethasone were continued thereafter until disease progression. There was no planned cross-over from the control arm to treatment with carfilzomib.
The study’s primary endpoint was progression-free survival. The median progression-free survival was significantly longer in the KRd arm than the Rd arm—26.3 months and 17.6 months, respectively (hazard ratio=0.69, P=0.0001).
At the time of analysis, the difference in overall survival did not reach the prespecified boundary for statistical significance.
The overall response rate was 87% in the KRd arm and 67% in the Rd arm. The median duration of response was 28.6 months and 21.2 months, respectively.
The rates of death due to adverse events (AEs) within 30 days of the last dose were similar between the treatment arms.
The most common causes of death not due to progressive disease occurring in patients in the KRd arm and the Rd arm, respectively, were cardiac disorders (3% vs 2%), infection (2% vs 3%), renal events (0% vs less than 1%), and other AEs (2% vs 3%).
Serious AEs were reported in 60% of patients in the KRd arm and 54% in the Rd arm. The most common serious AEs reported in the KRd arm and the Rd arm, respectively, were pneumonia (14% vs 11%), respiratory tract infection (4% vs 2%), pyrexia (4% vs 2%), and pulmonary embolism (3% vs 2%).
Global development
In the US, carfilzomib is approved for use in combination with lenalidomide and dexamethasone to treat MM patients who have received 1 to 3 prior lines of therapy.
Carfilzomib also has accelerated approval in the US as a single agent to treat MM patients who have received at least 2 prior therapies, including bortezomib and an immunomodulatory agent, and have demonstrated disease progression on or within 60 days of the completion of last therapy.
Amgen plans to submit data from the phase 3 ENDEAVOR trial for potential authorization of carfilzomib in combination with dexamethasone in the EU.
This data serves as the basis of the supplemental new drug application of carfilzomib in combination with dexamethasone for patients with relapsed MM, which has been accepted for priority review in the US.
In addition to the US and EU, carfilzomib is approved for use in Argentina, Israel, Kuwait, Mexico, Thailand, and Colombia. Additional regulatory applications for the drug have been submitted to health authorities worldwide.