Amgen To Present New Kyprolis® (carfilzomib) Data At 15th International Myeloma Workshop

Additional Data From Phase 3 ASPIRE Trial Including Age Analysis and Quality of Life Results

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Sep 23, 2015, 09:15 ET

THOUSAND OAKS, Calif., Sept. 23, 2015 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today announced the presentation of several studies evaluating Kyprolis^® (carfilzomib) for Injection, a next-generation proteasome inhibitor, at the 15^th International Myeloma Workshop (IMW), from Sept. 23-26, 2015, in Rome. Kyprolis is approved in the United States (U.S.) for use in combination with lenalidomide and dexamethasone for the treatment of relapsed multiple myeloma, an incurable blood cancer. In the European Union (EU), Kyprolis is under accelerated assessment with the European Medicines Agency (EMA).

"Multiple myeloma has historically been one of the most difficult to treat diseases because of the inherent complexities related to the recurring pattern of remission and relapse," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "Data to be presented at IMW will help provide further insight into the potential of Kyprolis as an important treatment option for patients living with relapsed multiple myeloma."

The following Amgen-sponsored abstracts will be presented at the meeting:

Kyprolis

Efficacy and Safety of Carfilzomib, Lenalidomide, and Dexamethasone (KRd) vs Lenalidomide and Dexamethasone (Rd) in Patients (Pts) With Relapsed Multiple Myeloma (RMM) Based on Age: Secondary Analysis From the Phase 3 Study ASPIRE (NCT01080391)
A. Palumbo, Abstract BP-051, Friday, Sept. 25, 6:40 p.m. - 7:40 p.m. CEST (Poster Area)
Superior Health-Related Quality of Life with Carfilzomib, Lenalidomide, and Dexamethasone versus Lenalidomide and Dexamethasone in Patients With Relapsed Multiple Myeloma (MM): Results From the ASPIRE Trial
A.K. Stewart, Abstract BP-052, Friday, Sept. 25, 6:40 - 7:40 p.m. CEST (Poster Area)

Observational

Survival Analysis in Newly Diagnosed Multiple Myeloma Patients in the United States Medicare Database
A. A. Yusuf, Abstract PO-171, Thursday, Sept. 24, 6:40 - 7:40 p.m. CEST (Poster Area)
Hospitalization Rates for Newly Diagnosed Multiple Myeloma Patients in the United States Medicare Database
A.A. Yusuf, Abstract PO-179, Thursday, Sept. 24, 6:40 - 7:40 p.m. CEST (Poster Area)

In the U.S., Kyprolis is approved as a monotherapy and in combination with lenalidomide and dexamethasone. In Mexico, Israel, Argentina and Thailand, Kyprolis is approved as monotherapy for relapsed, refractory multiple myeloma. In the EU, Kyprolis is under accelerated assessment with the EMA. The EMA application for Kyprolis is based on data from the Phase 3 ASPIRE (CArfilzomib, Lenalidomide, and DexamethaSone versus Lenalidomide and Dexamethasone for the treatment of PatIents with Relapsed Multiple MyEloma) trial and other relevant data. The study showed that patients treated with Kyprolis in combination with Revlimid^® (lenalidomide) and low-dose dexamethasone (regimen referred to as KRd) lived 50 percent longer (8.7 months) without their disease worsening compared to patients treated with lenalidomide and low-dose dexamethasone alone (regimen referred to as Rd). The median progression free survival was 26.3 months in those treated with KRd compared to 17.6 months in those treated with Rd (HR=0.69; 95 percent CI: 0.57-0.83; p<0.0001). The most common adverse events in the Kyprolis arm included pneumonia (1 percent), myocardial infarction (0.8 percent) and upper respiratory tract infection (0.8 percent).

About Multiple Myeloma
Multiple myeloma is the second most common hematologic cancer.¹ Worldwide, more than 230,000 people are living with multiple myeloma with approximately 114,000 new cases diagnosed and 80,000 people dying of the disease each year.^2,3In the U.S., there are nearly 96,000 people living with, or in remission from, multiple myeloma.⁴ The estimated number of new cases of multiple myeloma in 2014 was more than 24,000 and the estimated number of deaths was 11,090.⁴In Europe, it is estimated that more than 89,000 people are living with multiple myeloma. Approximately 39,000 new cases were diagnosed and 24,000 people died in 2012.³

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 low-dose dexamethasone, versus lenalidomide and low-dose dexamethasone alone, in patients with relapsed multiple myeloma following treatment with one to three prior regimens. The primary endpoint of the trial was progression-free survival (PFS), defined as the time from treatment initiation to disease progression or death. Secondary endpoints included overall survival (OS), overall response rate (ORR), duration of response (DOR), disease control rate, health-related quality of life (HR-QoL) and safety. Patients were randomized to receive Kyprolis (20 mg/m² on days 1 and 2 of cycle one only, escalating to 27 mg/m² subsquently), in addition to a standard dosing schedule of lenalidomide (25 mg per day for 21 days on, 7 days off) and low-dose dexamethasone (40 mg per week in 4 week cycles), versus lenalidomide and low-dose dexamethasone alone. In the Kyprolis arm, patients were given a 10 minute infusion on days 1, 2, 8, 9, 15 and 16. Kyprolis was omitted on days 8 and 9 during cycles 13-18 and not administered beyond 18 cycles.The study randomized 792 patients at sites in North America, Europe and Israel.

The OS results did not cross the pre-specified early stopping boundary for the interim analysis. At the time of the interim analysis, there were 143 deaths (36.1 percent) in the KRd group, compared to 162 deaths (40.9 percent) in the Rd group. The ORR was 87 percent with KRd and 67 percent with Rd. In the KRd and Rd groups, 32 percent versus 9 percent of patients achieved a complete response or higher (stringent complete response [sCR] or complete response [CR]), a measurement indicating depth of response. Median DOR was 28.6 months for patients receiving KRd (95 percent CI, 24.9 to 31.3 months) and 21.2 months for patients receiving Rd (95 percent CI, 16.7 to 25.8 months).

The rate of deaths due to adverse events (AEs) within 30 days of the last dose was balanced between the KRd arm and the Rd arm. The most common causes of death occurring in patients in the KRd arm compared to the Rd arm included cardiac disorders (3 percent versus 2 percent), infection (2 percent versus 3 percent), renal (0 percent versus less than 1 percent) and other AEs (2 percent versus 3 percent). Serious AEs were reported in 60 percent of the patients in the KRd arm and 54 percent of the patients in the Rd arm. The most common serious AEs reported in the KRd arm compared to the Rd arm were pneumonia (14 percent versus 11 percent), respiratory tract infection (4 percent versus 1.5 percent), pyrexia (4 percent versus 2 percent) and pulmonary embolism (3 percent versus 2 percent). Discontinuation due to any AE occurred in 26 percent of patients in the KRd arm versus 25 percent of patients in the Rd arm. Adverse events leading to discontinuation of Kyprolis occurred in 12 percent of patients.

The ASPIRE data were presented at the 56^th Annual Meeting of the American Society of Hematology and published in The New England Journal of Medicine in December 2014.

About Kyprolis^® (carfilzomib) for Injection
Kyprolis^® (carfilzomib) for Injection is indicated 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. Clinical benefit, such as improvement in survival or symptoms, has not been verified.

Kyprolis is a product of Onyx Pharmaceuticals, Inc. Onyx Pharmaceuticals is a subsidiary of Amgen and holds development and commercialization rights to Kyprolis globally, excluding Japan. Kyprolis is also approved for use in Argentina, Israel, Mexico and Thailand. For more information about Kyprolis, visit www.kyprolis.com.

Important Safety Information Regarding Kyprolis^® (carfilzomib) for Injection U.S. Indication
This safety information is specific to the current U.S. approved indication.

Cardiac Toxicities
New onset or worsening of preexisting 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. Death due to cardiac arrest has occurred within a day of Kyprolis administration.

Withhold Kyprolis for Grade 3 or 4 cardiac adverse events until recovery, and consider whether to restart Kyprolis based on a benefit/risk assessment.

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, and conduction abnormalities may be at greater risk for cardiac complications.

Acute Renal Failure
Cases of acute renal failure and renal insufficiency adverse events (renal impairment, acute renal failure, 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. This risk was greater in patients with a baseline reduced estimated creatinine clearance. 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 and should be based on an assessment of the patient's underlying risks, treatment regimen, and clinical status.

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.

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. Reduce or withhold dose as appropriate.

Thrombotic Thrombocytopenic Purpura / Hemolytic Uremic Syndrome (TTP/HUS)
Cases of 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 neuroradiological 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.

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 and the potential hazard to the fetus if Kyprolis is used during pregnancy.

ADVERSE REACTIONS
The most common adverse events occurring in at least 20% of patients treated with Kyprolis in monotherapy trials: anemia, fatigue, thrombocytopenia, nausea, pyrexia, decreased platelets, dyspnea, diarrhea, decreased lymphocyte, headache, decreased hemoglobin, cough, edema peripheral.

The most common adverse events occurring in at least 20% of patients treated with Kyprolis in the combination therapy trial: decreased lymphocytes, decreased absolute neutrophil count, decreased phosphorus, anemia, neutropenia, decreased total white blood cell count, decreased platelets, diarrhea, fatigue, thrombocytopenia, pyrexia, muscle spasm, cough, upper respiratory tract infection, decreased hemoglobin, hypokalemia.

Full prescribing information is available at www.kyprolis.com.

About Amgen
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 biologics manufacturing 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.

For more information, visit www.amgen.com and follow us on www.twitter.com/amgen.

Forward Looking Statements
This news release contains forward-looking statements that are based on the current expectations and beliefs of Amgen Inc. and its subsidiaries (Amgen) and are subject to a number of risks, uncertainties and assumptions that could cause actual results to differ materially from those described. All statements, other than statements of historical fact, are statements that could be deemed forward-looking statements, including estimates of revenues, operating margins, capital expenditures, cash, other financial metrics, expected legal, arbitration, political, regulatory or clinical results or practices, customer and prescriber patterns or practices, reimbursement activities and outcomes and other such estimates and results. Forward-looking statements involve significant risks and uncertainties, including those discussed below and more fully described in the Securities and Exchange Commission (SEC) reports filed by Amgen Inc., including Amgen Inc.'s most recent annual report on Form 10-K and any subsequent periodic reports on Form 10-Q and Form 8-K. Please refer to Amgen Inc.'s most recent Forms 10-K, 10-Q and 8-K for additional information on the uncertainties and risk factors related to Amgen's business. Unless otherwise noted, Amgen is providing this information as of Sept. 23, 2015, and expressly disclaims any duty to update information contained in this news release.

No forward-looking statement can be guaranteed and actual results may differ materially from those Amgen projects. Discovery or identification of new product candidates or development of new indications for existing products cannot be guaranteed and movement from concept to product is uncertain; consequently, there can be no guarantee that any particular product candidate or development of a new indication for an existing product will be successful and become a commercial product. Further, preclinical results do not guarantee safe and effective performance of product candidates in humans. The complexity of the human body cannot be perfectly, or sometimes, even adequately modeled by computer or cell culture systems or animal models. The length of time that it takes for Amgen and its partners to complete clinical trials and obtain regulatory approval for product marketing has in the past varied and Amgen expects similar variability in the future. Amgen develops product candidates internally and through licensing collaborations, partnerships and joint ventures. Product candidates that are derived from relationships may be subject to disputes between the parties or may prove to be not as effective or as safe as Amgen may have believed at the time of entering into such relationship. Also, Amgen or others could identify safety, side effects or manufacturing problems with Amgen's products after they are on the market. Amgen's business may be impacted by government investigations, litigation and product liability claims. If Amgen fails to meet the compliance obligations in the corporate integrity agreement between Amgen and the U.S. government, Amgen could become subject to significant sanctions. Amgen depends on third parties for a significant portion of its manufacturing capacity for the supply of certain of its current and future products and limits on supply may constrain sales of certain of its current products and product candidate development.

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Revlimid^® is registered trademark of Celgene Corporation.

CONTACT: Amgen, Thousand Oaks
Kristen Davis, 805-447-3008 (media)
Kristen Neese, 805-313-8267 (media)
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