Kyprolis Helped Patients Live 8.7 Months Longer Without Their Disease Worsening
Results to Form Basis of Regulatory Filings Beginning in 1H 2015

Thousand Oaks, California and South San Francisco, California (Press Release) Amgen (NASDAQ:AMGN) and its sub­sid­i­ary, Onyx Pharma­ceu­ticals, Inc., today announced that a planned interim analysis demon­strated that the Phase 3 clin­i­cal trial ASPIRE (CArfilzomib, Lena­lido­mide, and DexamethaSone versus Lena­lido­mide and Dexamethasone for the treat­ment of PatIents with Relapsed Multiple MyEloma) met its pri­mary end­point of pro­gres­sion-free survival (PFS). Patients treated with Kyprolis® (car­filz­o­mib) for Injection in com­bi­na­tion with Revlimid® (lena­lido­mide) and low-dose dexa­meth­a­sone (KRd) lived sig­nif­i­cantly longer without their disease worsening (median 26.3 months) compared to patients treated with Revlimid and low-dose dexa­meth­a­sone (Rd) (median 17.6 months) (HR=0.690, 95 per­cent CI, 0.570, 0.834, p<0.0001). While the data for over­all survival, a sec­ond­ary end­point, are not yet mature, the analysis showed a trend in favor of KRd that did not reach statistical sig­nif­i­cance.

The safety profile observed in this study is con­sis­tent with the current U.S. Kyprolis label, in­­clud­ing the rate of cardiac events. Treatment dis­con­tinu­a­tion due to adverse events and on-study deaths were com­parable be­tween the two arms. No new safety signals were identified.

Results will be submitted for presentation at the upcoming 56th Annual Meeting of the American Society of Hematology later this year.

"We are excited about these clin­i­cal results and the positive prospects they suggest for patients with multiple myeloma," said Robert A. Bradway, chairman and chief exec­u­tive officer of Amgen, adding, "Our mission at Amgen is to serve patients by ad­vanc­ing medicines that address serious disease. Kyprolis is an im­por­tant build­ing block in our robust, dif­fer­en­ti­ated pipe­line."

Bradway further explained, "Coupled with our recent U.S. regu­la­tory sub­missions for ivabradine and talimo­gene laherparepvec and our upcoming regu­la­tory sub­missions for evolocumab and blinatumomab, our pipe­line con­tinues to show notable progress."

Results from the ASPIRE study will form the basis for regu­la­tory sub­missions throughout the world be­gin­ning in the first half of 2015. In the U.S., the data may sup­port the conversion of accelerated approval to full approval and expand the current indi­ca­tion.

"In the treat­ment of patients with multiple myeloma, periods of remission become shorter fol­low­ing each treat­ment regi­men, underscoring the need for new options. The results of the ASPIRE study dem­onstrate that Kyprolis can sig­nif­i­cantly extend the time patients live without their disease progressing," said Pablo J. Cagnoni, M.D., pres­i­dent, Onyx Pharma­ceu­ticals, Inc. "The ability of novel ther­a­pies to produce deep and durable responses may, one day, transform this uniformly fatal disease to one that is chronic and man­age­able."

Onyx conducted the ASPIRE study under a Special Protocol Assessment (SPA) from the U.S. Food and Drug Admin­istra­tion (FDA) and has received Scientific Advice from the European Medicines Agency (EMA) on the design and planned analysis of the study.

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, defined as the time from treat­ment initiation to disease pro­gres­sion or death. Secondary end­points in­cluded over­all survival, over­all response rate, duration of response, disease control rate, health-related quality of life, and safety. Patients were ran­dom­ized to receive Kyprolis (20mg/m2 on days 1 and 2 of cycle 1 only, then 27mg/m2 sub­se­quently), in addi­tion to a standard dosing schedule of lena­lido­mide (25mg per day for 21 days on, 7 days off) and low-dose dexa­meth­a­sone (40mg per week in 4 week cycles), versus lena­lido­mide and low-dose dexa­meth­a­sone alone. The study ran­dom­ized 792 patients at sites in North America, Europe, and Israel.

About Multiple Myeloma

Multiple myeloma is the second most common hema­to­logic cancer and results from an ab­nor­mal­ity of plasma cells, usually in the bone marrow. In the U.S., approx­i­mately 70,000 people are living with multiple myeloma and approx­i­mately 24,000 new cases are diag­nosed annually.[1] Worldwide, nearly 230,000 people are living with multiple myeloma and approx­i­mately 114,000 new cases are diag­nosed annually.[2] In Europe, approx­i­mately 89,000 people are living with multiple myeloma, and approx­i­mately 39,000 new cases are diag­nosed annually.[3]

About Kyprolis® (car­filz­o­mib) for Injection

On July 20, 2012, the FDA granted accelerated approval of Kyprolis® (car­filz­o­mib) for Injection for the treat­ment of patients with multiple myeloma who have received at least two prior ther­a­pies in­­clud­ing bor­tez­o­mib and an immuno­modu­la­tory agent (IMiD), and have dem­onstrated disease pro­gres­sion on or within 60 days of completion of the last ther­apy. Approval was based on response rate. Clinical benefit, such as im­prove­ment in survival or symp­toms, has not been verified.

Kyprolis is marketed in the U.S. by Onyx Pharma­ceu­ticals, Inc., an Amgen sub­sid­i­ary.

Important Safety Information Regarding Kyprolis® (car­filz­o­mib) for Injection

Safety data have been eval­u­ated in 526 patients with re­lapsed and/or refractory multiple myeloma who received single-agent Kyprolis. There were 37 deaths in the Phase 2 studies, or 7% of patients. The most common causes of death, other than disease pro­gres­sion, were cardiac (5 patients), end-organ failure (4 patients), and in­fec­tion (4 patients). Important warnings and precautions in­clude cardiac arrest, congestive heart failure, myo­cardial ischemia; pul­mo­nary hyper­tension, pul­mo­nary com­pli­ca­tions, infusion reac­tions, tumor lysis syn­drome, thrombo­cytopenia, hepatic toxicity and embryo-fetal toxicity.

Death due to cardiac arrest has occurred within a day of Kyprolis admin­istra­tion. Patients with New York Heart Association Class III and IV heart failure, myo­cardial infarction in the preceding 6 months, and con­duc­tion ab­nor­mal­i­ties uncontrolled by medications were not eli­gible for the clin­i­cal trials. These patients may be at greater risk for cardiac com­pli­ca­tions.

Pulmonary arterial hyper­tension (PAH) was reported in 2% of patients treated with Kyprolis and was Grade 3 or greater in less than 1% of patients. Dyspnea was reported in 35% of patients enrolled in clin­i­cal trials. Grade 3 dyspnea occurred in 5%; no Grade 4 events, and 1 death (Grade 5) was reported.

Infusion reac­tions, char­ac­ter­ized by a spectrum of systemic symp­toms in­­clud­ing fever, chills, arthralgia, myalgia, facial flushing, facial edema, vomiting, weakness, shortness of breath, hypo­­tension, syncope, chest tightness, or angina can occur im­medi­ately fol­low­ing or up to 24 hours after admin­istra­tion of Kyprolis. Admin­istra­tion of dexa­meth­a­sone prior to Kyprolis reduces the incidence and severity of reac­tions. Tumor lysis syn­drome (TLS) occurred fol­low­ing Kyprolis admin­istra­tion in < 1% of patients. Patients with multiple myeloma and a high tumor burden should be con­sidered to be at greater risk for TLS.

Thrombocytopenia fol­low­ing Kyprolis admin­istra­tion resulted in a dose reduction in 1% of patients and dis­con­tinu­a­tion of treat­ment with Kyprolis in < 1% of patients.

Cases of hepatic failure, in­­clud­ing fatal cases, have been reported (< 1%). Kyprolis can cause elevations of serum transaminases and bilirubin.

There are no adequate and well-controlled studies in pregnant women using Kyprolis. Females of re­pro­duc­tive poten­tial should be advised to avoid becoming pregnant while being treated with Kyprolis.

The most common serious adverse reac­tions were pneu­monia, acute renal failure, pyrexia, and congestive heart failure. The most common adverse reac­tions (incidence of 30% or greater) observed in clin­i­cal trials of patients with multiple myeloma were fatigue, anemia, nausea, thrombo­cytopenia, dyspnea, diarrhea, and pyrexia. Serious adverse reac­tions were reported in 45% of patients.

Full pre­scrib­ing in­­for­ma­tion is avail­able at http://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 the world's largest independent bio­technology com­pany, 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.

About Onyx Pharma­ceu­ticals, Inc.

Based in South San Francisco, California, Onyx Pharma­ceu­ticals, Inc., an Amgen sub­sid­i­ary, is a global bio­pharma­ceu­tical com­pany engaged in the devel­op­ment and com­mer­cial­iza­tion of inno­va­tive ther­a­pies for im­prov­ing the lives of people with cancer. The com­pany is focused on devel­op­ing novel medicines that target key molecular path­ways. For more in­­for­ma­tion about Onyx, visit the com­pany's website at www.onyx.com. Onyx Pharma­ceu­ticals is on Twitter. Sign up to follow our Twitter feed @OnyxPharm at http://twitter.com/OnyxPharm.

REVLIMID® is a registered trademark of Celgene Corpo­ra­tion.

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 Aug. 4, 2014 and expressly disclaims any duty to update in­­for­ma­tion con­tained in this news release.

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In addi­tion, sales of Amgen's prod­ucts (including prod­ucts of Amgen's wholly-owned sub­sid­i­aries) are affected by the reim­burse­ment policies imposed by third-party payers, in­­clud­ing gov­ern­ments, private insurance plans and man­aged care providers and may be affected by regu­la­tory, clin­i­cal and guideline devel­op­ments and domestic and inter­na­tional trends to­ward man­aged care and health­care cost con­tainment as well as U.S. legislation affecting pharma­ceu­tical pricing and reim­burse­ment. Government and others' reg­u­la­tions and reim­burse­ment policies may affect the devel­op­ment, usage and pricing of Amgen's prod­ucts. In addi­tion, Amgen competes with other com­pa­nies with respect to some of its marketed prod­ucts as well as for the discovery and devel­op­ment of new prod­ucts. Amgen believes that some of its newer prod­ucts, prod­uct can­di­dates or new indi­ca­tions for existing prod­ucts, may face com­pe­ti­tion when and as they are approved and marketed. Amgen's prod­ucts may compete against prod­ucts that have lower prices, estab­lish­ed reim­burse­ment, superior per­for­mance, are easier to admin­ister, or that are other­wise competitive with its prod­ucts. In addi­tion, while Amgen and its partners routinely obtain patents for their prod­ucts and tech­nology, the protection of Amgen's prod­ucts offered by patents and patent appli­ca­tions may be chal­lenged, invalidated or circumvented by its com­pet­i­tors and there can be no guar­an­tee of Amgen's or its partners' ability to obtain or main­tain patent protection for Amgen's prod­ucts or prod­uct can­di­dates. Amgen cannot guar­an­tee that it will be able to produce commercially suc­cess­ful prod­ucts or main­tain the commercial success of its existing prod­ucts. Amgen's stock price may be affected by actual or perceived market oppor­tu­ni­ty, competitive position, and success or failure of its prod­ucts or prod­uct can­di­dates. Further, the discovery of sig­nif­i­cant problems with a prod­uct similar to one of Amgen's prod­ucts that implicate an entire class of prod­ucts could have a ma­teri­al adverse effect on sales of the affected prod­ucts and on Amgen's business and results of operations. Amgen's efforts to integrate the operations of com­pa­nies it has acquired may not be suc­cess­ful. Cost saving ini­tia­tives may result in Amgen incurring im­pair­ment or other related charges on its assets. Amgen may ex­peri­ence dif­fi­culties, delays or unexpected costs and not achieve antic­i­pated cost savings from its recently announced restructuring plans. Amgen's business per­for­mance could affect or limit the ability of Amgen's Board of Directors to declare a dividend or their ability to pay a dividend or repurchase Amgen common stock.

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[1] National Cancer Institute. SEER Stat Fact Sheets: Myeloma. Available at http://seer.cancer.gov/statfacts/html/mulmy.html.
[2] Inter­na­tional Agency for Research on Cancer, GLOBOCAN 2012 database. Available at http://globocan.iarc.fr/.
[3]Cancer Research UK. "Myeloma Incidence Statistics." Available at: http://www.cancerresearchuk.org/cancer-info/cancerstats/types/myeloma/incidence/uk-multiple-myeloma-incidence-statistics#europeandworldwide.

Source: Amgen.