Long-Term Analysis Of Phase 3 Head-To-Head Study Confirms KYPROLIS® (Carfilzomib) Regimen Extends Overall Survival In Patients With Relapsed Multiple Myeloma Amgen (NASDAQ: AMGN) today announced positive results from a post-hoc analysis requested by the U.S. Food and Drug Administration (FDA) of the Phase...

THOUSAND OAKS, Calif. , Aug. 30, 2017 /PRNewswire/ -- Amgen (NASDAQ: AMGN ) today announced positive results from a post-hoc analysis requested by the U.S. Food and Drug Administration (FDA) of the Phase 3 head-to-head ENDEAVOR trial, which followed patients for at least three years after enrollment. The analysis evaluated overall survival (OS) and long-term safety of KYPROLIS ® (carfilzomib) administered at 56 mg/m 2 twice weekly and dexamethasone (Kd) versus Velcade ® (bortezomib) and dexamethasone (Vd) in patients with relapsed or refractory multiple myeloma. Kd reduced the risk of death by 24 percent over Vd (median OS 47.8 months for Kd versus 38.8 months for Vd, HR=0.76, 95 percent CI, 0.63-0.92; p =0.0017). This Kd regimen is currently approved in the U.S., European Union and other countries based on the primary analysis of progression-free survival in the ENDEAVOR study.

"We are excited about the three-year follow-up of the ENDEAVOR study as the overall survival benefit reflects both the efficacy and the long-term safety of this KYPROLIS regimen in patients with relapsed multiple myeloma," said Sean E. Harper , M.D., executive vice president of Research and Development at Amgen. "These results confirm that when a patient relapses, KYPROLIS should replace Velcade as a standard-of-care."

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, hypertension, dyspnea, fatigue, cough, insomnia, upper respiratory tract infection, nausea, bronchitis, asthenia, back pain, thrombocytopenia, edema peripheral, headache and muscle spasms.

Results from the primary ENDEAVOR OS analysis were recently published online in The Lancet Oncology. Data showed Kd reduced the risk of death by 21 percent over Vd. Patients treated with KYPROLIS lived 7.6 months longer than those treated with Velcade (median OS 47.6 months for Kd versus 40.0 months for Vd, HR=0.79, 95 percent CI, 0.65-0.96). On Aug. 30, 2017 , Amgen announced the FDA accepted for review the supplemental New Drug Application (sNDA) for KYPROLIS to include OS data from the Phase 3 head-to-head ENDEAVOR trial in the product information. The FDA has set a Prescription Drug User Fee Act (PDUFA) action date of April 30 , 2018.

Since its approval in 2012, more than 50,000 patients worldwide have received KYPROLIS. The KYPROLIS clinical program continues to focus on providing solutions for physicians and patients in treating 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.

The randomized ENDEAVOR (Randomiz E d, Ope N Label, Phase 3 Study of Carfilzomib Plus DE xameth A sone V s Bortezomib Plus Dexamethas O ne in Patients With R elapsed Multiple Myeloma) trial of 929 patients evaluated Kd versus Vd 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. 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/m 2 on days 1 and 2, and if tolerated was escalated to 56 mg/m 2 from day 8 cycle one onwards. Patients who received bortezomib (1.3 mg/m 2 ) with low-dose dexamethasone (20 mg) were treated with bortezomib administered subcutaneously or intravenously at the discretion of the investigator and in accordance with regional 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 Multiple Myeloma

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. 2,3 In the U.S., there are nearly 95,000 people living with, or in remission from, multiple myeloma. 4 Approximately 30,330 Americans are diagnosed with multiple myeloma each year and 12,650 patient deaths are reported on an annual basis. 4

About KYPROLIS ® (carfilzomib)

Proteasomes play an important role in cell function and growth by breaking down proteins that are damaged or no longer needed. 5 KYPROLIS has been shown to block proteasomes, leading to an excessive build-up of proteins within cells. 5 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. 5,6

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

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

Acute Renal Failure

Tumor Lysis Syndrome

Pulmonary Toxicity

Pulmonary Hypertension

Venous Thrombosis

Infusion Reactions

Thrombocytopenia

Hepatic Toxicity and Hepatic Failure

Thrombotic Microangiopathy

Posterior Reversible Encephalopathy Syndrome (PRES)

Increased Fatal and Serious Toxicities in Combination with Melphalan and Prednisone in Newly Diagnosed Transplant ‐ ineligible Patients

Embryo-fetal Toxicity

ADVERSE REACTIONS

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.

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.

Forward-Looking Statements

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CONTACT: Amgen, Thousand Oaks Kristen Davis , 805-447-3008 (Media) Kristen Neese , 805-313-8267 (Media) Arvind Sood , 805-447-1060 (Investors)