The European Commission approved an expanded indication for Kyprolis Amgen (of carfilzomib) for the treatment of patients with multiple myeloma relapse

The European Commission approved an expanded indication for Kyprolis Amgen (of carfilzomib) for the treatment of patients with multiple myeloma relapse -

Amgen announced that the European Commission (EC) approved a variation of the marketing authorization for Kyprolis® (carfilzomib) to include the use in combination with dexamethasone alone for patients with multiple myeloma adults who received at least one prior therapy. Prolonged marks the second indication for Kyprolis approval by the EC in less than a year.
"In the Phase 3 head-to-head, Kyprolis in combination with dexamethasone doubled the time patients lived without their cancer progressing and the complete response rate compared to bortezomib and dexamethasone, "said Sean E. Harper, MD, executive vice president of research and development at Amgen." Kyprolis based schemes have shown the superiority of two old options of therapeutic standard of care for patients relapsed myeloma, strengthening Kyprolis place as a fundamental therapy in this patient population. "
The EC approved the expanded indication for Kyprolis based on data from the Phase 3 head-to-head ENDEAVOR in which multiple myeloma patients treated with Kyprolis plus dexamethasone (Kd) with superior progression free survival (PFS) of 18.7 months against 9.4 months in those receiving bortezomib plus dexamethasone (Vd) (HR = 0.53; 95 percent CI: 0.44, 0.65; p <0 .0001="" 6.2="" against="" also="" better="" compared="" complete="" demonstrated="" double="" em="" endpoints="" for="" improvement="" in="" including="" kd="" on="" or="" patients="" percent="" rate="" response="" secondary="" the="" those="" to="" treated="" vd="" were="" which="" with=""> p

<0 .0001="" 20="" 28="" 2="" 32="" 36="" 4="" 8="" a="" adverse="" and="" anemia="" bortezomib="" both="" but="" ci:="" common="" cough="" diarrhea="" dose-limiting="" dyspnea="" edema.="" events="" experienced="" fatigue="" frequent="" grade="" groups="" higher="" in="" infection="" kd="" kyprolis="" lower="" most="" nausea="" neuropathy="" occurred="" of="" or="" p="" patients="" percent="" peripheral="" profile="" pyrexia="" rate="" reactions="" receiving="" respectively="" respiratory="" safety="" significantly="" similar="" than="" that="" the="" those="" thrombocytopenia="" toxicity="" tract="" treated="" vd="" vs.="" was="" were="" with="">
Kyprolis was first approved by the EC in November 2015 for use in combination with lenalidomide and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy based on results of the ASPIRE study. Today's approval by the EC following the approval of the US Food and Drug Administration of a New Drug Application extra based on the results of ENDEAVOR in January 2016.
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 represents approximately one percent of all cancers worldwide.2-4 in Europe, approximately 39,000 patients are diagnosed with multiple myeloma each year and 24,000 patient deaths are reported annually basis.5
about ENDEAVOR
The randomized ENDEAVOR (Randomiz E d, Ope N label, phase 3 study carfilzomib more dE xameth A sone V s bortezomib more Dexamethas O not in patients R elapsed multiple myeloma) trial of 929 patients evaluated Kyprolis in combination with low-dose dexamethasone, versus bortezomib with low-dose dexamethasone in patients with myeloma multiple relapsed after at least one but no more than three prior therapies. The primary outcome of the trial endpoint was PFS, defined as the time between the start of treatment until disease progression or death. In a clinical trial, the measurement of the PFS is a way to demonstrate how a works.6 treatment
As noted above, Kyprolis with dexamethasone (Kd) was superior to bortezomib and dexamethasone (Vd) and demonstrated much longer PFS. Improvement in PFS in the Kd arm relative to Vd arm was seen through the pre-specified key subgroups including patients naive bortezomib those cytogenetic high or standard risk and with or without prior transplantation .
In terms of secondary endpoints, Kd achieved an overall response rate higher than Vd (76.9 percent against 62.6 percent; p <0 .0001="" 28.6="" 54.3="" a="" achieved="" and="" better="" bortezomib="" em="" good="" group="" in="" kyprolis="" of="" or="" partial="" patients="" percent="" response="" very=""> p
<0 .0001="" and="" are="" be="" continue="" data="" mature="" monitored.="" not="" overall="" p="" respectively.="" survival="" to="" yet=""> Discontinuation due to adverse events and deaths on the study were comparable between the two arms.7 A number of adverse reactions to known drugs were reported at a higher rate Kyprolis in the bortezomib group compared to the group, including any grade dyspnea, hypertension, pyrexia, and cough as were all grades of heart failure (group term; 8 percent against 3 percent) and acute renal failure (group term; 8 percent against 5 percent) .7
adverse event rate of 3 or higher degree were 73 percent in the Kyprolis group and 67 percent in the group7 bortezomib adverse events higher interest in Kyprolis and grade 3 or bortezomib groups included hypertension (preferred term, 9 percent against 3 percent), dyspnea (preferred term; 5 percent against 2 percent), heart failure (group term; 5 per cent against 2 per cent), acute renal failure (group term; 4 percent against 3 percent), ischemic heart disease (group term; 2 per cent against 2 per cent) and pulmonary arterial hypertension ( grouped term, 0.6 percent against 0.2 percent) .7
patients received treatment until progression with Kyprolis in 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 day 1 and 2, and if tolerated followed by escalation to 56 mg / m2 on day 8. Patients who tolerated 56 mg / m2 cycle 1 were maintained at this dose for subsequent cycles. Patients who received bortezomib (1.3 mg / m2) with low-dose dexamethasone (20 mg) were administered subcutaneous or intravenous bortezomib at the discretion of the investigator and in accordance with regulatory approval of bortezomib. Over 75 percent of patients in the control arm received bortezomib subcutaneously. This study was conducted in 235 sites worldwide. For more 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 more needed .8 Kyprolis has been shown to block proteasome, leading to an excessive accumulation of proteins in cells.8 in some cells Kyprolis can cause cell death, particularly in myeloma cells because they are more likely to contain greater proteins.8,9 abnormal amount of
Kyprolis is approved in the US for the following:

• in combination with dexamethasone or lenalidomide plus dexamethasone for the treatment of patients multiple myeloma relapsed or refractory who received a three-line treatment.
• as a single agent for the treatment of multiple myeloma patients with relapsed or refractory who received one or more lines of therapy.

Kyprolis is also approved in Argentina, Israel, Kuwait, Mexico, Thailand, Colombia, Korea, Canada, Switzerland, Russia, Brazil and the European Union. Additional regulatory applications for Kyprolis are ongoing and have been submitted to health authorities worldwide.
For more information on the United States, please visit www.kyprolis.com.
Important EU Product Safety Information
This medicine 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 anticancer therapy. The most serious side effects that may occur during treatment Kyprolis include: cardiac toxicity, pulmonary toxicity, pulmonary hypertension, dyspnea, hypertension, including hypertensive crisis, acute renal failure, lysis syndrome tumor, reactions infusion, 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 a full European Prescribing Information.
Important US Safety Information
cardiac toxicities

• The emergence or worsening of pre- existing heart failure (such as congestive heart failure, pulmonary edema, decreased ejection fraction), restrictive cardiomyopathy, myocardial ischemia, myocardial infarction, including deaths after KYPROLIS administration. Some events occurred in patients whose ventricular function normal basis. Death due to cardiac arrest has occurred within a day of KYPROLIS administration.
• Monitor patients for signs or symptoms of heart or clinical ischemic heart failure. quickly assess if cardiac toxicity is suspected. Abstention KYPROLIS 4 adverse cardiac events until grade 3 or recovery, and restart KYPROLIS consider the reduction in the level 1 of the dose based on a benefit / risk assessment.
• While adequate hydration is necessary before each dose cycle 1, monitor all patients for volume overload of signs, particularly in patients at risk of heart failure. Adjust total fluid intake in clinical status in patients with a baseline heart failure or who are at risk of heart failure.
• Patients ≥ 75 years, the risk of heart failure increases. Patients with New York Heart Association Class III and IV heart failure, recent myocardial infarction, conduction abnormalities, angina or arrhythmia may be at increased risk of cardiac complications and should have a medical evaluation complete (including blood pressure and fluid management) before starting treatment with KYPROLIS and remain under close monitoring.

acute renal failure

• cases of acute renal failure and renal failure adverse events (including renal failure) were observed in patients receiving KYPROLIS. Acute renal failure have been reported more frequently in patients with advanced relapsed and refractory multiple myeloma who received monotherapy KYPROLIS. Monitor renal function with regular measurement of serum creatinine and / or creatinine clearance estimated. Reduce or hold the dose as appropriate.

Tumor lysis syndrome

• Cases of tumor Lysis Syndrome (TLS), including fatal outcome, have occurred in patients receiving KYPROLIS. Multiple myeloma and a high tumor burden should be considered a higher risk for TLS. Adequate hydration is necessary before each dose at cycle 1, and in subsequent cycles as needed. Consider uric acid lowering drugs in patients at risk of TLS. Monitor TLS evidence during treatment and manage quickly. Abstention KYPROLIS up TLS is solved.

Pulmonary toxicity

• Distress Acute Respiratory Syndrome (ARDS), acute respiratory failure, and acute pulmonary infiltrative diffuse disease like pneumonia and interstitial lung disease occurred in patients receiving KYPROLIS. Some events have been fatal. If pulmonary toxicity induced by medication, stop KYPROLIS.

Pulmonary hypertension

• Pulmonary arterial hypertension (PAH) has been reported in patients treated with KYPROLIS. To assess cardiac imaging and / or other tests as indicated. Abstention KYPROLIS for PAH until resolved or returned to baseline and consider restarting KYPROLIS based on a benefit / risk assessment.

Dyspnea

• Dyspnea was reported in patients treated with KYPROLIS. Evaluate dyspnea exclude cardiopulmonary conditions, including heart failure and pulmonary syndromes. Stop KYPROLIS for grade 3 or 4 dyspnea until resolved or returned to baseline. Consider whether to restart KYPROLIS based on a benefit / risk assessment.

Hypertension

• Hypertension, including hypertensive crisis and hypertensive emergency, was observed with KYPROLIS. Some of these events have been fatal. regularly monitor blood pressure in all patients. If hypertension can not be adequately controlled, retain and assess KYPROLIS. Consider whether to restart KYPROLIS based on a benefit / risk assessment.

venous thrombosis

• venous thromboembolic events (including deep vein thrombosis and pulmonary embolism) were observed with KYPROLIS. VTE prophylaxis is recommended for patients treated with the combination of KYPROLIS with dexamethasone or lenalidomide plus dexamethasone. The thromboprophylaxis regimen should be based on an evaluation of the underlying risks of the patient.
• Patients using oral contraceptives or hormonal contraceptive method associated with a risk of thrombosis should consider another method of effective contraception during treatment with KYPROLIS in combination with dexamethasone or lenalidomide associated with dexamethasone .

infusion reactions

• infusion reactions, including life-threatening reactions have occurred in patients receiving KYPROLIS. Symptoms include fever, chills, arthralgia, myalgia, facial flushing, facial edema, vomiting, weakness, shortness of breath, hypotension, syncope, chest tightness, or angina. These reactions can occur immediately following or up to 24 hours after administration of KYPROLIS. Premedication with dexamethasone to reduce the incidence and severity of infusion reactions. Inform patients of the risks and symptoms of infusion reactions and contact immediately if they occur a doctor.

thrombocytopenia

• KYPROLIS causes thrombocytopenia with platelet recovery basis usually have the beginning of the next cycle. Thrombocytopenia has been reported in patients receiving KYPROLIS. Monitor platelet counts frequently during treatment with KYPROLIS. Reduce or hold the dose as appropriate.

liver failure and liver toxicity

• Cases of hepatic failure, including fatal cases, have been reported during treatment with KYPROLIS. KYPROLIS may cause an increase in serum transaminases. Monitor liver enzymes regularly regardless of the reference values. Reduce or hold the dose as appropriate.

thrombotic microangiopathy

• Cases of thrombotic microangiopathy, including thrombotic thrombocytopenic purpura / hemolytic uremic syndrome (TTP / HUS), including the fatal outcome occurred in patients receiving KYPROLIS. Monitor for signs and symptoms of TTP / HUS. KYPROLIS stop if the diagnosis is suspected. If the diagnosis of TTP / HUS is excluded KYPROLIS can be restarted. The safety of resuming KYPROLIS therapy in previously challenging TTP / HUS patients is not known.

Syndrome posterior reversible encephalopathy (PRES)

• Cases of PRES have occurred in patients receiving KYPROLIS. NEAR was formerly known as reversible posterior leukoencephalopathy syndrome. Consider a neuro-radiological imaging (MRI) for the appearance of visual or neurological symptoms. KYPROLIS stop if PRES is suspected and evaluated. The safety of resuming KYPROLIS treatment in patients previously SEPR experience is not known.

Toxicity embryofoetal

• KYPROLIS may cause fetal harm when administered to a pregnant woman based on its mechanism of action and results in animals.
• Females of reproductive potential should be advised to avoid becoming pregnant during treatment with KYPROLIS. The males of reproductive potential should be advised to avoid fathering a child during treatment with KYPROLIS. If this drug is used during pregnancy, or if pregnancy occurs while taking this drug, the patient should be informed of the potential hazard to the fetus.

ADVERSE REACTIONS

• The most common adverse reactions occurring in at least 20% of patients treated with KYPROLIS in trials of combination therapy: anemia, neutropenia, diarrhea, dyspnea, fatigue, thrombocytopenia, pyrexia, insomnia, muscle spasms, cough, upper. respiratory infection, hypokalemia

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, peripheral edema.
full prescribing information for the United States is available www.kyprolis.com.
about Amgen
Amgen is committed to unlocking the potential of biology for patients with severe disease by discovering, developing, manufacturing and delivery of innovative human therapeutics. This approach begins by using tools such as advanced human genetics to unravel the complexities of the disease and to understand the basis of human biology.
Amgen focuses on areas of unmet medical needs and uses its expertise to work for solutions that improve health outcomes and dramatically improve people's lives. A biotechnology pioneer since 1980, Amgen has grown to become a leading independent biotech companies in the world, has reached millions of patients worldwide and develops a drug pipeline with a potential breakaway. < br />