On January 17, 2018 Amgen (NASDAQ:AMGN) reported that the U.S. Food and Drug Administration (FDA) has approved the supplemental New Drug Application (sNDA) to add overall survival (OS) data from the Phase 3 head-to-head ENDEAVOR trial to the Prescribing Information for KYPROLIS (carfilzomib) (Press release, Amgen, JAN 17, 2018, View Source;p=RssLanding&cat=news&id=2327111 [SID1234523235]). Data added to the label demonstrated that KYPROLIS and dexamethasone (Kd) reduced the risk of death by 21 percent and increased OS by 7.6 months versus Velcade (bortezomib) and dexamethasone (Vd) in patients with relapsed or refractory multiple myeloma (median OS 47.6 months for Kd versus 40.0 months for Vd, HR=0.79; p=0.01).

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"Overall survival is generally considered to be the gold standard of endpoints because it clearly demonstrates a drug’s value in extending a patient’s life, 1,2" said David M. Reese, M.D., senior vice president of Translational Sciences and Oncology at Amgen. "Blood cancer therapies approved by the FDA between 2003 and 2013 only improved overall survival by an average of 2.61 months.3 KYPROLIS and dexamethasone improved overall survival by 7.6 months, underscoring that this regimen is a significant advancement and should be considered a standard of care for patients with relapsed or refractory multiple myeloma."

The National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (NCCN Guidelines) list Kd as the only preferred doublet regimen at relapse for multiple myeloma. Full OS results from the ENDEAVOR trial were published earlier this year in The Lancet Oncology.

Adverse events observed in this updated analysis were consistent with those previously reported for ENDEAVOR. The most common adverse events (greater than or equal to 20 percent) in the KYPROLIS arm were anemia, diarrhea, pyrexia, dyspnea, fatigue, hypertension, cough, insomnia, upper respiratory tract infection, peripheral edema, nausea, bronchitis, asthenia, back pain, thrombocytopenia and headache.

Since its approval in 2012, more than 50,000 patients worldwide have received KYPROLIS. The KYPROLIS clinical program continues to focus on providing treatment options for physicians and patients for this frequently relapsing and difficult-to-treat cancer. KYPROLIS is available for patients whose myeloma has relapsed or become resistant to another treatment and continues to be studied in a range of combinations and patient populations.

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 Velcade with low-dose dexamethasone in relapsed or refractory patients who previously received at least one, but not more than three, prior therapeutic regimens. The primary endpoint of the trial was progression-free survival, defined as the time from treatment initiation to disease progression or death. The primary analysis was published in The Lancet Oncology and is described in the Prescribing Information.

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 one only, KYPROLIS was administered at 20 mg/m2 on days 1 and 2, and if tolerated was escalated to 56 mg/m2 from day 8 of cycle one onwards. Patients who received Velcade (1.3 mg/m2) with low-dose dexamethasone (20 mg) were treated with Velcade administered subcutaneously or intravenously at the discretion of the investigator and in accordance with regional regulatory approval of Velcade. More than 75 percent of the patients in the control arm received Velcade 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 Multiple Myeloma
Multiple myeloma is an incurable blood cancer, characterized by a recurring pattern of remission and relapse.4 It is a rare and life-threatening disease that accounts for approximately one percent of all cancers.5,6 In the U.S., there are more than 118,000 people living with, or in remission from, multiple myeloma.7 Approximately 30,280 Americans are diagnosed with multiple myeloma each year and 12,590 patient deaths are reported on an annual basis.7

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:

In combination with dexamethasone or with lenalidomide plus dexamethasone for the treatment of patients with relapsed or refractory multiple myeloma who have received one to three lines of therapy.
As a single agent for the treatment of patients with relapsed or refractory multiple myeloma who have received one or more lines of therapy.
KYPROLIS is also approved in Argentina, Australia, Bahrain, Canada, Hong Kong, Israel, Japan, Kuwait, Lebanon, Macao, Mexico, Thailand, Colombia, S. Korea, Canada, Qatar, Switzerland, United Arab Emirates, Turkey, Russia, Brazil, India, Oman and the European Union. Additional regulatory applications for KYPROLIS are underway and have been submitted to health authorities worldwide.

IMPORTANT SAFETY INFORMATION

Cardiac Toxicities

New onset or worsening of pre-existing cardiac failure (e.g., congestive heart failure, pulmonary edema, decreased ejection fraction), restrictive cardiomyopathy, myocardial ischemia, and myocardial infarction including fatalities have occurred following administration of KYPROLIS. Some events occurred in patients with normal baseline ventricular function. Death due to cardiac arrest has occurred within one day of KYPROLIS administration.
Monitor patients for clinical signs or symptoms of cardiac failure or cardiac ischemia. Evaluate promptly if cardiac toxicity is suspected. Withhold KYPROLIS for Grade 3 or 4 cardiac adverse events until recovery, and consider whether to restart KYPROLIS at 1 dose level reduction based on a benefit/risk assessment.
While 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, conduction abnormalities, angina, or arrhythmias may be at greater risk for cardiac complications and should have a comprehensive medical assessment (including blood pressure and fluid management) prior to starting treatment with KYPROLIS and remain under close follow-up.
Acute Renal Failure

Cases of acute renal failure and renal insufficiency adverse events (including renal failure) have occurred in patients receiving KYPROLIS. Acute renal failure was reported more frequently in patients with advanced relapsed and refractory multiple myeloma who received KYPROLIS monotherapy. Monitor renal function with regular measurement of the serum creatinine and/or estimated creatinine clearance. Reduce or withhold dose as appropriate.
Tumor Lysis Syndrome

Cases of Tumor Lysis Syndrome (TLS), including fatal outcomes, have occurred in patients receiving KYPROLIS. Patients with multiple myeloma and a high tumor burden should be considered at greater risk for TLS. Adequate hydration is required prior to each dose in Cycle 1, and in subsequent cycles as needed. Consider uric acid lowering drugs in patients at risk for TLS. Monitor for evidence of TLS during treatment and manage promptly. Withhold KYPROLIS until TLS is resolved.
Pulmonary Toxicity

Acute Respiratory Distress Syndrome (ARDS), acute respiratory failure, and acute diffuse infiltrative pulmonary disease such as pneumonitis and interstitial lung disease have occurred in patients receiving KYPROLIS. Some events have been fatal. In the event of drug-induced pulmonary toxicity, discontinue KYPROLIS.
Pulmonary Hypertension

Pulmonary arterial hypertension (PAH) was reported in patients treated with KYPROLIS. Evaluate with cardiac imaging and/or other tests as indicated. Withhold KYPROLIS for PAH until resolved or returned to baseline and consider whether to restart KYPROLIS based on a benefit/risk assessment.
Dyspnea

Dyspnea was reported in patients treated with KYPROLIS. Evaluate dyspnea to exclude cardiopulmonary conditions including cardiac 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, has been observed with KYPROLIS. Some of these events have been fatal. It is recommended to control hypertension prior to starting KYPROLIS. Monitor blood pressure regularly in all patients. If hypertension cannot be adequately controlled, withhold KYPROLIS and evaluate. Consider whether to restart KYPROLIS based on a benefit/risk assessment.
Venous Thrombosis

Venous thromboembolic events (including deep venous thrombosis and pulmonary embolism) have been observed with KYPROLIS. Thromboprophylaxis is recommended for patients being treated with the combination of KYPROLIS with dexamethasone or with lenalidomide plus dexamethasone. The thromboprophylaxis regimen should be based on an assessment of the patient’s underlying risks.
Patients using oral contraceptives or a hormonal method of contraception associated with a risk of thrombosis should consider an alternative method of effective contraception during treatment with KYPROLIS in combination with dexamethasone or lenalidomide plus 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. Premedicate with dexamethasone to reduce the incidence and severity of infusion reactions. Inform patients of the risk and of symptoms of an infusion reaction and to contact a physician immediately if they occur.
Hemorrhage

Fatal or serious cases of hemorrhage have been reported in patients receiving KYPROLIS. Hemorrhagic events have included gastrointestinal, pulmonary, and intracranial hemorrhage and epistaxis. Promptly evaluate signs and symptoms of blood loss. Reduce or withhold dose as appropriate.
Thrombocytopenia

KYPROLIS causes thrombocytopenia with recovery to baseline platelet count usually by the start of the next cycle. Thrombocytopenia was reported in patients receiving KYPROLIS. Monitor platelet counts frequently during treatment with KYPROLIS. Reduce or withhold dose as appropriate.
Hepatic Toxicity and Hepatic Failure

Cases of hepatic failure, including fatal cases, have been reported during treatment with KYPROLIS. KYPROLIS can cause increased serum transaminases. Monitor liver enzymes regularly regardless of baseline values. Reduce or withhold dose as appropriate.
Thrombotic Microangiopathy

Cases of thrombotic microangiopathy, including thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS), including fatal outcome have occurred in patients receiving KYPROLIS. Monitor for signs and symptoms of TTP/HUS. Discontinue KYPROLIS if diagnosis is suspected. If the diagnosis of TTP/HUS is excluded, KYPROLIS may be restarted. The safety of reinitiating KYPROLIS therapy in patients previously experiencing TTP/HUS is not known.
Posterior Reversible Encephalopathy Syndrome (PRES)

Cases of PRES have occurred in patients receiving KYPROLIS. PRES was formerly known as Reversible Posterior Leukoencephalopathy Syndrome. Consider a neuro-radiological imaging (MRI) for onset of visual or neurological symptoms. Discontinue KYPROLIS if PRES is suspected and evaluate. The safety of reinitiating KYPROLIS therapy in patients previously experiencing PRES is not known.
Increased Fatal and Serious Toxicities in Combination with Melphalan and Prednisone in Newly Diagnosed Transplant‐ineligible Patients

In a clinical trial of transplant‐ineligible patients with newly diagnosed multiple myeloma comparing KYPROLIS, melphalan, and prednisone (KMP) vs bortezomib, melphalan, and prednisone (VMP), a higher incidence of serious and fatal adverse events was observed in patients in the KMP arm. KYPROLIS in combination with melphalan and prednisone is not indicated for transplant‐ineligible patients with newly diagnosed multiple myeloma.
Embryo-fetal Toxicity

KYPROLIS can cause fetal harm when administered to a pregnant woman based on its mechanism of action and findings in animals.
Females of reproductive potential should be advised to avoid becoming pregnant while being treated with KYPROLIS. Males of reproductive potential should be advised to avoid fathering a child while being treated with KYPROLIS. If this drug is used during pregnancy, or if pregnancy occurs while taking this drug, the patient should be apprised 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 the combination therapy trials: anemia, neutropenia, diarrhea, dyspnea, fatigue, thrombocytopenia, pyrexia, insomnia, muscle spasm, cough, upper respiratory tract 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, edema peripheral.
Please see full prescribing information at www.kyprolis.com.

About Amgen’s Commitment to Oncology
Amgen Oncology is committed to helping patients take on some of the toughest cancers, such as those that have been resistant to drugs, those that progress rapidly through the body and those where limited treatment options exist. Amgen’s supportive care treatments help patients combat certain side effects of strong chemotherapy, and our targeted medicines and immunotherapies focus on more than a dozen different malignancies, ranging from blood cancers to solid tumors. With decades of experience providing therapies for cancer patients, Amgen continues to grow its portfolio of innovative and biosimilar oncology medicines.

On January 17, 2018 Amgen (NASDAQ:AMGN) reported that the Journal of Clinical Oncology published positive overall survival (OS) findings from the final analysis of the Phase 3 ASPIRE trial, which demonstrated that the addition of KYPROLIS (carfilzomib) to lenalidomide and dexamethasone (KRd) reduced the risk of death by 21 percent versus lenalidomide and dexamethasone alone (Rd) and extended OS by 7.9 months in patients with relapsed or refractory multiple myeloma (median OS 48.3 months for KRd versus 40.4 months for Rd, HR = 0.79, 95 percent CI, 0.67 – 0.95; 1-sided p=0.0045) (Press release, Amgen, JAN 17, 2018, View Source;p=RssLanding&cat=news&id=2327105 [SID1234523234]). Notably, an OS improvement of 11.4 months was observed for patients at first relapse (47.3 versus 35.9 months [HR = 0.81, 95 percent CI, 0.62 – 1.06]), supporting early use of KRd.

"Results from the final analysis of the Phase 3 ASPIRE trial published today in the Journal of Clinical Oncology are significant, as they further validate carfilzomib, lenalidomide and dexamethasone as a standard of care regimen for patients with relapsed or refractory multiple myeloma," said Keith Stewart, M.B., Ch.B., Mayo Clinic in Arizona and principal investigator of the ASPIRE trial. "Furthermore, these data showed that early use of carfilzomib, lenalidomide and dexamethasone at first relapse provided nearly one additional year of survival for patients regardless of prior treatment with bortezomib or transplant."

"As seen in two different Phase 3 studies, KYPROLIS-based regimens are the first and only therapy combinations to demonstrate a significant overall survival advantage for patients with relapsed or refractory multiple myeloma versus recent standards of care," said David M. Reese, M.D., senior vice president of Translational Sciences and Oncology at Amgen. "We look forward to continuing conversations with regulatory authorities in the U.S. and Europe to add these results to the KYPROLIS label."

The safety data from ASPIRE was consistent with the known safety profile of KYPROLIS. The most common adverse events (greater than or equal to 20 percent) in the KYPROLIS arm were diarrhea, anemia, neutropenia, fatigue, upper respiratory tract infection, pyrexia, cough, hypokalemia, thrombocytopenia, muscle spasms, pneumonia, nasopharyngitis, nausea, constipation, insomnia and bronchitis.

The final analysis of ASPIRE included subgroup analyses by prior lines of therapy, prior Velcade (bortezomib) exposure at first relapse, and prior transplant at first relapse. Among these three groups, there was an 18 to 29 percent reduction in the risk of death for KRd versus Rd, consistent with findings in the overall population. Median OS was 11.4 months longer for KRd versus Rd in patients who had received one prior line of therapy and 6.5 months longer for patients with two or more prior lines (48.8 versus 42.3 months [HR = 0.79, 95 percent CI, 0.62 – 0.99]). Among patients who had received one prior line, median OS was improved by 12 months with KRd versus Rd in those with prior Velcade exposure (45.9 versus 33.9 months [HR = 0.82; 95 percent CI, 0.56 – 1.19]) and by 7.9 months in those without prior Velcade (48.3 versus 40.4 months [HR = 0.80, 95 percent CI, 0.55 – 1.17]). Median OS was also improved by 18.6 months with KRd versus Rd among patients with prior transplantation at first relapse (57.2 versus 38.6 months [HR = 0.71, 95 percent CI, 0.48 –1.05]).

The KRd regimen used in this trial is currently approved in the U.S., European Union and other countries based on primary analysis of progression-free survival (PFS) in the ASPIRE study. Amgen has submitted a supplemental New Drug Application to the U.S. Food and Drug Administration and a variation to the marketing application to the European Medicines Agency to include the OS data from ASPIRE in the product information for KYPROLIS.

About ASPIRE
The international, randomized Phase 3 ASPIRE (CArfilzomib, Lenalidomide, and DexamethaSone versus Lenalidomide and Dexamethasone for the treatment of PatIents with Relapsed Multiple MyEloma) trial evaluated KYPROLIS in combination with lenalidomide and dexamethasone, versus lenalidomide and dexamethasone alone, in patients with relapsed or refractory multiple myeloma following treatment with one to three prior regimens. The primary endpoint of the trial was PFS, defined as the time from treatment initiation to disease progression or death. Secondary endpoints included OS, overall response rate, duration of response, disease control rate, health-related quality of life and safety. Patients were randomized to receive KYPROLIS (20 mg/m2 on days 1 and 2 of cycle one, escalating to 27 mg/m2 on days 8, 9, 15 and 16 of cycle one and continuing on days 1, 2, 8, 9, 15 and 16 of subsequent cycles), in addition to a standard dosing schedule of lenalidomide (25 mg per day for 21 days on, seven days off) and low-dose dexamethasone (40 mg per week in four-week cycles), versus lenalidomide and low-dose dexamethasone alone. The study randomized 792 patients at sites in North America, Europe and Israel.

Patients treated with KRd reported improved global health status, with higher Global Health Status/Quality of Life (QoL) scores compared with Rd over 18 cycles of treatment (2‑sided p<0.0001) measured with the EORTC QLQ‑C30, an instrument validated in multiple myeloma.

Overall survival by Revised International Staging System (R-ISS) stage was also assessed. For R-ISS stage I (KRd, n = 42; Rd, n = 46), median OS was not reached for KRd and was 58 months for Rd (HR = 0.49, 95 percent CI, 0.26 – 0.92). For patients with R-ISS stage II (KRd, n = 194; Rd, n = 195), median OS was 45.4 months for KRd and 41.2 months for Rd (4.2 months; HR = 0.86, 95 percent CI, 0.68 – 1.10). For the small number of patients with R-ISS stage III (KRd, n = 37; Rd, n = 47), median OS was 23.3 months for KRd and 18.8 months for Rd (4.5 months; HR = 1.05, 95 percent CI, 0.66 – 1.68).

For the overall study population, treatment discontinuation due to an adverse event occurred in 19.9 percent of patients treated with KRd and 21.5 percent of patients receiving Rd. Fatal adverse events were reported in 11.5 percent of KRd-treated patients and 10.5 percent of patients treated with Rd. Grade ≥3 adverse event rates were 87 percent for KRd and 83 percent for Rd. Selected grade ≥3 adverse events of interest (grouped terms; KRd vs Rd) included acute renal failure (3.8 percent versus 3.3 percent), cardiac failure (4.3 percent versus 2.1 percent), and hypertension (6.4 percent versus 2.3 percent).

About Multiple Myeloma
Multiple myeloma is an incurable blood cancer, characterized by a recurring pattern of remission and relapse.1 It is a rare and life-threatening disease that accounts for approximately one percent of all cancers. 2,3 Worldwide, approximately 114,000 people are diagnosed with multiple myeloma each year and 80,000 patient deaths are reported on an annual basis.2

About KYPROLIS (carfilzomib)
Proteasomes play an important role in cell function and growth by breaking down proteins that are damaged or no longer needed.4 KYPROLIS has been shown to block proteasomes, leading to an excessive build-up of proteins within cells.4 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. 4,5

KYPROLIS is approved in the U.S. for the following:

In combination with dexamethasone or with lenalidomide plus dexamethasone for the treatment of patients with relapsed or refractory multiple myeloma who have received one to three lines of therapy.
As a single agent for the treatment of patients with relapsed or refractory multiple myeloma who have received one or more lines of therapy.
KYPROLIS is also approved in Argentina, Australia, Bahrain, Canada, Hong Kong, Israel, Japan, Kuwait, Lebanon, Macao, Mexico, Thailand, Colombia, S. Korea, Canada, Qatar, Switzerland, United Arab Emirates, Turkey, Russia, Brazil, India, Oman and the European Union. Additional regulatory applications for KYPROLIS are underway and have been submitted to health authorities worldwide.

IMPORTANT SAFETY INFORMATION

Cardiac Toxicities

New onset or worsening of pre-existing cardiac failure (e.g., congestive heart failure, pulmonary edema, decreased ejection fraction), restrictive cardiomyopathy, myocardial ischemia, and myocardial infarction including fatalities have occurred following administration of KYPROLIS. Some events occurred in patients with normal baseline ventricular function. Death due to cardiac arrest has occurred within one day of KYPROLIS administration.
Monitor patients for clinical signs or symptoms of cardiac failure or cardiac ischemia. Evaluate promptly if cardiac toxicity is suspected. Withhold KYPROLIS for Grade 3 or 4 cardiac adverse events until recovery, and consider whether to restart KYPROLIS at 1 dose level reduction based on a benefit/risk assessment.
While 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, conduction abnormalities, angina, or arrhythmias may be at greater risk for cardiac complications and should have a comprehensive medical assessment (including blood pressure and fluid management) prior to starting treatment with KYPROLIS and remain under close follow-up.
Acute Renal Failure

Cases of acute renal failure and renal insufficiency adverse events (including renal failure) have occurred in patients receiving KYPROLIS. Acute renal failure was reported more frequently in patients with advanced relapsed and refractory multiple myeloma who received KYPROLIS monotherapy. Monitor renal function with regular measurement of the serum creatinine and/or estimated creatinine clearance. Reduce or withhold dose as appropriate.
Tumor Lysis Syndrome

Cases of Tumor Lysis Syndrome (TLS), including fatal outcomes, have occurred in patients receiving KYPROLIS. Patients with multiple myeloma and a high tumor burden should be considered at greater risk for TLS. Adequate hydration is required prior to each dose in Cycle 1, and in subsequent cycles as needed. Consider uric acid lowering drugs in patients at risk for TLS. Monitor for evidence of TLS during treatment and manage promptly. Withhold KYPROLIS until TLS is resolved.
Pulmonary Toxicity

Acute Respiratory Distress Syndrome (ARDS), acute respiratory failure, and acute diffuse infiltrative pulmonary disease such as pneumonitis and interstitial lung disease have occurred in patients receiving KYPROLIS. Some events have been fatal. In the event of drug-induced pulmonary toxicity, discontinue KYPROLIS.
Pulmonary Hypertension

Pulmonary arterial hypertension (PAH) was reported in patients treated with KYPROLIS. Evaluate with cardiac imaging and/or other tests as indicated. Withhold KYPROLIS for PAH until resolved or returned to baseline and consider whether to restart KYPROLIS based on a benefit/risk assessment.
Dyspnea

Dyspnea was reported in patients treated with KYPROLIS. Evaluate dyspnea to exclude cardiopulmonary conditions including cardiac 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, has been observed with KYPROLIS. Some of these events have been fatal. Monitor blood pressure regularly in all patients. If hypertension cannot be adequately controlled, withhold KYPROLIS and evaluate. Consider whether to restart KYPROLIS based on a benefit/risk assessment.
Venous Thrombosis

Venous thromboembolic events (including deep venous thrombosis and pulmonary embolism) have been observed with KYPROLIS. Thromboprophylaxis is recommended for patients being treated with the combination of KYPROLIS with dexamethasone or with lenalidomide plus dexamethasone. The thromboprophylaxis regimen should be based on an assessment of the patient’s underlying risks.
Patients using oral contraceptives or a hormonal method of contraception associated with a risk of thrombosis should consider an alternative method of effective contraception during treatment with KYPROLIS in combination with dexamethasone or lenalidomide plus 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. Premedicate with dexamethasone to reduce the incidence and severity of infusion reactions. Inform patients of the risk and of symptoms of an infusion reaction and to contact a physician immediately if they occur.
Hemorrhage

Fatal or serious cases of hemorrhage have been reported in patients receiving KYPROLIS. Hemorrhagic events have included gastrointestinal, pulmonary, and intracranial hemorrhage and epistaxis. Promptly evaluate signs and symptoms of blood loss. Reduce or withhold dose as appropriate.
Thrombocytopenia

KYPROLIS causes thrombocytopenia with recovery to baseline platelet count usually by the start of the next cycle. Thrombocytopenia was reported in patients receiving KYPROLIS. Monitor platelet counts frequently during treatment with KYPROLIS. Reduce or withhold dose as appropriate.
Hepatic Toxicity and Hepatic Failure

Cases of hepatic failure, including fatal cases, have been reported during treatment with KYPROLIS. KYPROLIS can cause increased serum transaminases. Monitor liver enzymes regularly regardless of baseline values. Reduce or withhold dose as appropriate.
Thrombotic Microangiopathy

Cases of thrombotic microangiopathy, including thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS), including fatal outcome have occurred in patients receiving KYPROLIS. Monitor for signs and symptoms of TTP/HUS. Discontinue KYPROLIS if diagnosis is suspected. If the diagnosis of TTP/HUS is excluded, KYPROLIS may be restarted. The safety of reinitiating KYPROLIS therapy in patients previously experiencing TTP/HUS is not known.
Posterior Reversible Encephalopathy Syndrome (PRES)

Cases of PRES have occurred in patients receiving KYPROLIS. PRES was formerly known as Reversible Posterior Leukoencephalopathy Syndrome. Consider a neuro-radiological imaging (MRI) for onset of visual or neurological symptoms. Discontinue KYPROLIS if PRES is suspected and evaluate. The safety of reinitiating KYPROLIS therapy in patients previously experiencing PRES is not known.
Increased Fatal and Serious Toxicities in Combination with Melphalan and Prednisone in Newly Diagnosed Transplant‐ineligible Patients

In a clinical trial of transplant‐ineligible patients with newly diagnosed multiple myeloma comparing KYPROLIS, melphalan, and prednisone (KMP) vs bortezomib, melphalan, and prednisone (VMP), a higher incidence of serious and fatal adverse events was observed in patients in the KMP arm. KYPROLIS in combination with melphalan and prednisone is not indicated for transplant‐ineligible patients with newly diagnosed multiple myeloma.
Embryo-fetal Toxicity

KYPROLIS can cause fetal harm when administered to a pregnant woman based on its mechanism of action and findings in animals.
Females of reproductive potential should be advised to avoid becoming pregnant while being treated with KYPROLIS. Males of reproductive potential should be advised to avoid fathering a child while being treated with KYPROLIS. If this drug is used during pregnancy, or if pregnancy occurs while taking this drug, the patient should be apprised 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 the combination therapy trials: anemia, neutropenia, diarrhea, dyspnea, fatigue, thrombocytopenia, pyrexia, insomnia, muscle spasm, cough, upper respiratory tract 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, edema peripheral.
Please see full prescribing information at www.kyprolis.com.

About Amgen’s Commitment to Oncology
Amgen Oncology is committed to helping patients take on some of the toughest cancers, such as those that have been resistant to drugs, those that progress rapidly through the body and those where limited treatment options exist. Amgen’s supportive care treatments help patients combat certain side effects of strong chemotherapy, and our targeted medicines and immunotherapies focus on more than a dozen different malignancies, ranging from blood cancers to solid tumors. With decades of experience providing therapies for cancer patients, Amgen continues to grow its portfolio of innovative and biosimilar oncology medicines.

On January 17, 2018 Aeterna Zentaris Inc. (NASDAQ:AEZS) (TSX:AEZS) reported that it has, through a wholly-owned subsidiary, entered into a license and assignment agreement with a wholly-owned subsidiary of Strongbridge Biopharma plc (NASDAQ:SBBP) to carry out development, manufacturing, registration and commercialization of Macrilen (macimorelin) in the United States and Canada (Press release, AEterna Zentaris, JAN 17, 2018, View Source [SID1234523233]).

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"We are very excited to partner with Strongbridge on the commercialization of Macrilen (macimorelin) in the U.S. and Canada," said Michael Ward, Chief Executive Officer of Aeterna Zentaris. "We look forward to exploring the various alternatives to monetizing our rights to Macimorelin outside the United States and Canada."

Aeterna Zentaris will receive an upfront cash payment of US$24,000,000 from Strongbridge, and, for as long as Macrilen (macimorelin) is patent-protected, Aeterna Zentaris will be entitled to a 15% royalty on net sales up to US$75,000,000 and an 18% royalty on net sales above US$75,000,000. Following the end of patent protection in United States or Canada for Macrilen (macimorelin), Aeterna Zentaris will be entitled to a 5% royalty on net sales in that country. In addition, Aeterna Zentaris will also receive one-time payments from Strongbridge following the first achievement of the following commercial milestone events:

US$4,000,000 on achieving US$25,000,000 annual net sales,
US$10,000,000 on achieving US$50,000,000 annual net sales,
US$20,000,000 on achieving US$100,000,000 annual net sales,
US$40,000,000 on achieving US$200,000,000 annual net sales, and
US$100,000,000 on achieving US$500,000,000 annual net sales.
Upon approval by the U.S. Food and Drug Administration ("FDA") of a pediatric indication for Macrilen (macimorelin), Aeterna Zentaris will receive a one-time milestone payment of US$5,000,000 from Strongbridge.

Strongbridge will fund 70% of the costs of a worldwide pediatric development program to be run by Aeterna Zentaris with customary oversight from a joint steering committee. The joint steering committee will be comprised of four persons, two of whom will be appointed by each of Strongbridge and Aeterna Zentaris.

The decision to license Macrilen (macimorelin) in the U.S. and Canada was made following a detailed review process undertaken by a committee of independent directors of Aeterna Zentaris. The committee of independent directors of Aeterna Zentaris was advised by Stifel, Nicolaus & Company, Incorporated. Aeterna Zentaris is continuing to explore various alternatives to monetizing its rights to Macimorelin in other countries around the globe, including whether to find other license partners in these jurisdictions or to use its internal resources to commercialize Macimorelin in one or more of these countries.

The Agreement will be filed on SEDAR at www.sedar.com. The foregoing description of the terms of the Agreement does not purport to be complete and is qualified in its entirety by reference to the Agreement.

Macrilen (macimorelin) is an orally-active ghrelin agonist that stimulates the secretion of growth hormone. Macrilen (macimorelin) has been granted orphan drug designation by the FDA for the evaluation of growth hormone deficiency. On December 20, 2017, the FDA granted Aeterna Zentaris marketing approval for Macrilen (macimorelin) to be used in the diagnosis of patients with adult growth hormone deficiency ("AGHD").

AGHD reportedly affects approximately 60,000 adults across the U.S. and Canada. Growth hormone not only plays an important role in growth from childhood to adulthood, but also helps promote a hormonally-balanced health status. AGHD mostly results from damage to the pituitary gland. It is usually characterized by a reduction in bone mineral density, lean body mass, exercise capacity, and overall quality of life as well as an increase of cardiovascular risks.

On January 17, 2018 Trillium Therapeutics Inc. (NASDAQ/TSX: TRIL), a clinical stage immuno-oncology company developing innovative therapies for the treatment of cancer, reported the following key additions to its leadership team (Press release, Trillium Therapeutics, JAN 17, 2018, View Source [SID1234523296]):

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Blythe Thomson, MD, Executive Medical Director
Jane E. Cole, RN, Senior Director, Clinical Operations
Brian E. Jahns, PharmD, Senior Vice President, Commercial and Business Development

The company also announced that Eric Sievers, MD, has transitioned from Chief Medical Officer to Senior Clinical Advisor. In this new role, Dr. Sievers will maintain a close association with the company’s clinical programs and advisors, and continue to assist Trillium with clinical strategy and communications. The company is now initiating the process of identifying Dr. Sievers’ successor.

"These additions to our management team further bolsters our planned pipeline development activities," said Dr. Niclas Stiernholm, President and CEO of Trillium Therapeutics. "Our new team members bring diverse and deep drug development expertise, and will have a major impact on the advancement of our TTI-621 program and corporate growth. Under Dr. Sievers’ guidance, our TTI-621 program has been well positioned for advancement in 2018. We look forward to continued benefit from Dr. Sievers’ expertise in his new role."

Dr. Thomson, a board certified pediatric hematologist/oncologist, has held multiple academic and industry appointments, most recently at Ariad Pharmaceuticals, Epizyme Inc. and Medpace. She brings a great depth of experience in all phases of clinical development of therapies for solid tumors and hematologic malignancies, and will oversee Trillium’s development programs, ensuring they are optimized for adaptability and efficiency. Dr. Thomson completed her medical training at Ohio State University and the Fred Hutchinson Cancer Research Center, University of Washington, and currently serves as an attending physician at Floating Hospital for Children, Tufts University School of Medicine.

Ms. Cole brings to Trillium over 25 years of experience, leadership and capability in the global execution of drug development programs. A registered nurse who pursued a career in drug development, Ms. Cole has led numerous development teams in executing Phase I through Phase IV clinical trials globally. She has previously held clinical operation roles in multinational pharma companies, including Hoffman-La Roche, as well as in smaller biotechnology and contract research organizations. In her current role she will oversee the company’s clinical operations team as well as its relationships with clinical research organizations. Ms. Cole joins Trillium from Chiltern International, where she was Project Director, Global Executive Lead.

Dr. Jahns has a wealth of experience in commercial activities, including long-term planning, strategic marketing, and working in an international matrix environment with partners in the United States, Canada and Europe. Drawing on his experiences as a pharmacist and an academic, and 18 years at Hoffmann-La Roche, he has been involved in the success of products such as Rituxan, Avastin, Zelboraf and Herceptin. Dr. Jahns will focus on developing partnership opportunities between Trillium and potential collaborators, and providing input on the company’s commercialization activities.

On January 17, 2018 RXi Pharmaceuticals Corporation (NASDAQ: RXII) a clinical-stage company developing a new class of RNAi-based therapeutics reported that it will give an oral presentation highlighting the company’s proprietary therapeutic platform at the Immuno-Oncology Frontiers World conference (Press release, RXi Pharmaceuticals, JAN 17, 2018, View Source [SID1234523194]). This exclusive Immuno-oncology (I-O) partnering event provides direct access to decision makers and KOL’s working towards the next oncology blockbuster. Also, this is the only I-O event co-located with the leading Cell and Gene Therapy global meeting; providing access to the most commercially advanced technical expertise specifically for cellular immunotherapies. The conference will take place January 22-25, 2018 at the Hyatt Regency in Miami, Florida.

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Title: Targeting Immune Checkpoints Using Self-Delivering RNAi (sd-rxRNA) Technology
Session: Stream 2- Emerging Science: Reprogramming the Tumor Microenvironment – Conquering Immune Suppressive Molecular Pathways
Date and Time: Tuesday, January 23, 2018, at 11:50 am ET
Presenter: James Cardia, Ph.D., Director of Business Development and Intellectual Property

The presentation will be available on the Company’s website approximately 1 hour after the presentation at www.rxipharma.com.

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About RXi’s self-delivering RNAi (sd-rxRNA) technology platform

sd-rxRNA, RXi’s proprietary self-delivering RNAi platform, is a single chemically modified compound with delivery and therapeutic properties built directly into the compound itself. The compound is asymmetrical with a phosphorothioate backbone and contains chemical modifications that provide for efficient cellular uptake and gene silencing. These compounds are potent, stable and specific, and demonstrated to be safe and active in a clinical setting.

RXi’s novel sd-rxRNA technology differs from natural and most synthetic RNA interference (RNAi) molecules in that they are chemically modified to allow for efficient internalization of the compounds by cells and silencing of the targeted genes. Importantly, unlike other naked siRNA compounds, delivery of sd-rxRNAs are not limited to a specific cell type. For local delivery and ex vivo cell-based therapeutic applications, our compounds do not require delivery vehicles. This is a major advantage since delivery vehicles can have related toxicity that affects cell viability. sd-rxRNA has demonstrated nearly 100 percent transfection efficiency with high cell viability in numerous cell types.