US Submission Designed to Support Conversion From Accelerated to Full FDA Approval and Expansion of Current Approved Indication
EMA Grants Kyprolis Accelerated Assessment and Orphan Drug Desig­na­tion

{{image}}Thousand Oaks, CA and South San Francisco, CA (Press Release) – Amgen (NASDAQ:AMGN) and its sub­sid­i­ary Onyx Pharma­ceu­ticals, Inc., today announced the sub­mission of a supple­mental New Drug Application (sNDA) to the U.S. Food and Drug Admin­istra­tion (FDA) and a Marketing Authorization Ap­pli­cation (MAA) to the European Medicines Agency (EMA) for Kyprolis® (car­filz­o­mib) for Injection to seek approval for the treat­ment of patients with re­lapsed multiple myeloma who have received at least one prior ther­apy. In the U.S., the sNDA is designed to sup­port the conversion of accelerated approval to full approval and expand the current approved indi­ca­tion. In the European Union (EU), Kyprolis received orphan drug desig­na­tion and the MAA has been granted accelerated assess­ment.

The sNDA and MAA are 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.

"Multiple myeloma is an incurable blood cancer that often becomes resistant to treat­ment, underscoring the need for new thera­peutic options that provide deep and durable responses to extend the time patients live without their disease progressing," said Pablo J. Cagnoni, M.D., pres­i­dent, Onyx Pharma­ceu­ticals, Inc. "The U.S. and EU sub­missions sup­port our goal of bringing Kyprolis to patients with re­lapsed multiple myeloma."

Orphan desig­na­tion is granted by the EMA for medicines intended for the treat­ment, prevention or diag­nosis of a disease that is life threatening and has a prev­a­lence in the EU of no more than five in 10,000. The in­tended medicine must aim to provide sig­nif­i­cant benefit to those affected by the con­di­tion.¹

Kyprolis is in a class of drugs called pro­te­a­some inhibitors and was granted accelerated approval by the FDA in 2012. Kyprolis is also approved for use in Argentina, Israel and Mexico.

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. Worldwide, nearly 230,000 people are living with multiple myeloma.² In 2012, ap­prox­i­mately 114,000 new cases were diag­nosed and 80,000 people died.³ In the U.S., ap­prox­i­mate­ly 83,000 people were living with multiple myeloma in 2011. The esti­mated number of new cases in 2014 was 24,000 and the esti­mated number of deaths was 11,000.⁴ In Europe, ap­prox­i­mate­ly 89,000 people are living with multiple myeloma.² Approximately 39,000 new cases were diag­nosed and 24,000 people died in 2012.²

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 (20 mg/m² on days 1 and 2 of cycle 1 only, escalating to 27 mg/m² on days 8, 9, 15 and 16 of cycle 1 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, 7 days off) and low-dose dexa­meth­a­sone (40 mg 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.

Onyx Pharma­ceu­ticals conducted the ASPIRE trial under a Special Protocol Assessment (SPA) from the FDA and received Scientific Advice from the EMA on the design and planned analysis of the study.

About Kyprolis® (car­filz­o­mib) for Injection

On July 20, 2012, the U.S. 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 a prod­uct of Onyx Pharma­ceu­ticals, Inc. Onyx Pharma­ceu­ticals is a sub­sid­i­ary of Amgen and holds devel­op­ment and com­mer­cial­iza­tion rights to Kyprolis globally, excluding Japan. For more in­­for­ma­tion about Kyprolis, visit www.kyprolis.com.

Important Safety Information Regarding Kyprolis® (car­filz­o­mib) for Injection

This safety in­­for­ma­tion is specific to the current U.S. approved indi­ca­tion, which is based on Phase 2 studies.

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 per­cent of patients. The most common causes of death, other than disease pro­gres­sion, were cardiac events (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 per­cent of patients treated with Kyprolis and was Grade 3 or greater in less than 1 per­cent of patients. Dyspnea was reported in 35 per­cent of patients enrolled in clin­i­cal trials. Grade 3 dyspnea occurred in 5 per­cent; 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

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

Cases of hepatic failure, in­­clud­ing fatal cases, have been reported (<1 per­cent). 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 per­cent 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 per­cent of patients.

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.

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.

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 Jan. 27, 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.

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.

The scientific in­­for­ma­tion discussed in this news release relating to new indi­ca­tions for Amgen's prod­ucts is pre­lim­i­nary and investigative and is not part of the labeling approved by the U.S. Food and Drug Ad­min­is­tra­tion (FDA) for the prod­ucts. The prod­ucts are not approved for the inves­ti­ga­tional use(s) discussed in this news release and no conclusions can or should be drawn re­gard­ing the safety or effectiveness of the prod­ucts for these uses.

References

1 European Medicines Agency. Orphan Desig­na­tion Page. http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/general_content_000029.jsp
2 Bray F, Ren JS, Masuyer E, Ferlay J. Estimates of global cancer prev­a­lence for 27 sites in the adult pop­u­la­tion in 2008. Int J Cancer. 2013 Mar. 1;132(5):1133-45. doi: 10.1002/ijc.27711. Epub 2012 Jul 26.
3 Ferlay J, et al. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: Inter­na­tional Agency for Research on Cancer; 2013. Available from: http://globocan.iarc.fr, accessed on 15/January/2015.
4 National Cancer Institute. SEER Stat Fact Sheets: Myeloma. http://seer.cancer.gov/statfacts/html/mulmy.html.

Source: Amgen.