Data from Once-Weekly CHAMPION Phase 1/2 Study Presented at ASCO

Thousand Oaks, CA (Press Release) – Amgen (NASDAQ: AMGN) today announced the initiation of the ARROW trial, a global Phase 3 study eval­u­ating the benefit of Kyprolis® (car­filz­o­mib) for Injection ad­min­is­tered once-weekly with dexa­meth­a­sone versus the current U.S. Food and Drug Admin­istra­tion (FDA) approved twice-weekly admin­istra­tion schedule in patients with re­lapsed and refractory multiple myeloma who have received prior treat­ment with bor­tez­o­mib and an immuno­modu­la­tory agent (IMiD). The trial was ini­ti­ated based on results from the Phase 1/2 CHAMPION study, which were presented (abstract no. 8527) at the 51st Annual Meeting of the American Society of Clinical Oncology (ASCO) on Sunday, May 31 at 8 a.m. CT.

Results from the Phase 1 and 2 portions of CHAMPION were presented for 104 patients (Phase 1, n=15; Phase 2, n=89) with re­lapsed or refractory multiple myeloma who had received one to three prior treat­ment regi­mens at the determined maximum tolerated dose (MTD) of 20/70 mg/m². In the Phase 2 portion of the study, the over­all response rate (ORR; defined as the per­cent­age of patients achieving a partial response or better) was 77 per­cent. The clin­i­cal benefit rate (CBR; defined as the per­cent­age of patients with minimal response or better) was 84 per­cent; the median time to response for patients who achieved a partial response or better was 1.6 months (range, 0.7-7.2); Kaplan-Meier median duration of response (DOR) was 15 months (95 per­cent CI 9-not estimable); and the Kaplan-Meier median pro­gres­sion-free survival (PFS) was 10.6 months (95 per­cent CI 9.0-16.1).

"The results from the CHAMPION Phase 1/2 study form the basis of the Phase 3 ARROW study with the goal of poten­tially providing patients and physicians greater convenience with a once-weekly dosing schedule of Kyprolis," said Sean E. Harper, M.D., exec­u­tive vice pres­i­dent of Research and Development at Amgen. "The initiation of this trial underscores our commitment to addressing the needs of patients with multiple myeloma through the entire treat­ment con­tin­uum."

The most common hema­to­logic treat­ment-emergent adverse events (AEs) of any grade were anemia (24 per­cent), thrombo­cytopenia (22 per­cent) and neu­tro­penia (8 per­cent). The most common non-hematologic treat­ment-emergent AEs of any grade were fatigue (52 per­cent), nausea (35 per­cent), headache and diarrhea (31 per­cent each). The most commonly occurring grade ≥3 hema­to­logic treat­ment-emergent AEs were thrombo­cytopenia (6 per­cent), anemia (5 per­cent) and neu­tro­penia (4 per­cent). The most common non-hematologic grade ≥3 treat­ment-emergent AEs were fatigue (11 per­cent), pneu­monia (7 per­cent), acute renal failure and hyper­tension (6 per­cent each). Adverse events grade ≥3 in­cluded cardiac failure (2 per­cent) and periph­eral neu­rop­athy (1 per­cent).

A total of 36 patients (35 per­cent) had at least one serious AE. Sixteen patients (15 per­cent) treated at the MTD had at least one car­filz­o­mib dose reduction due to AEs, and 10 patients (10 per­cent) dis­con­tinued study treat­ment due to AEs. Ten patients (10 per­cent) dis­con­tinued treat­ment due to investigator's discretion, 12 patients (12 per­cent) dis­con­tinued due to patient de­ci­sion and 34 patients (33 per­cent) dis­con­tinued due to progressive disease. A total of five patients died during the study, all of which were in the Phase 2 portion of the study: one patient each had cause of death reported as car­dio­pul­mo­nary arrest, pneu­monia, disease pro­gres­sion, acute res­pira­tory distress syn­drome and acute kidney injury.

About CHAMPION

The CHAMPION (Community Harmonized Assessment of Myeloma Patients via an Integrated Oncology Network) trial is a Phase 1/2, multi­center, single-arm, non-randomized, open-label and dose-escalation study of weekly Kyprolis with dexa­meth­a­sone for patients with re­lapsed or refractory multiple myeloma. The pri­mary objective of the Phase 1 portion of the study was to determine the MTD of once-weekly Kyprolis with dexa­meth­a­sone. The pri­mary objective of the Phase 2 portion of the study was to determine the ORR. Secondary end­points were to eval­u­ate the CBR, PFS, time to pro­gres­sion and DOR. Patients who received one to three prior treat­ment regi­mens were eli­gible to enroll. The last patient was enrolled in September 2014, and the data cutoff date for analyses presented at ASCO was May 1, 2015. A total of 48 per­cent of enrolled patients were bor­tez­o­mib-refractory, 28 per­cent were lena­lido­mide-refractory and 16 per­cent were refractory to both bor­tez­o­mib and lena­lido­mide. In the Phase 1 portion, patients received Kyprolis as a 30-minute in­tra­venous (IV) infusion on days 1, 8 and 15 of a 28-day cycle using a standard 3+3 dose-escalation scheme. Patients received Kyprolis at 20 mg/m² on day 1 of cycle 1. Subsequent doses started at 45 mg/m² and were escalated to 56, 70 or 88 mg/m² beginning on day 8 of cycle 1 until the MTD of 20/70 mg/m² was reached for use in the Phase 2 portion. Patients received dexa­meth­a­sone 40 mg (IV or oral) on days 1, 8, 15 and 22 of cycles 1–8; dexa­meth­a­sone was omitted on day 22 beginning in cycle 9. Treatment was ad­min­is­tered until disease pro­gres­sion or unacceptable toxicity was observed.

For more in­­for­ma­tion about CHAMPION, please visit www.clinicaltrials.gov under trial identi­fi­ca­tion number NCT01677858.

About ARROW

The ARROW (RAndomized, Open-label, Phase 3 Study in Subjects with Relapsed and Refractory Multiple Myeloma Receiving Carfilzomib in Combination with Dexamethasone, Comparing Once-Weekly versus Twice-weekly Carfilzomib Dosing) trial is eval­u­ating approx­i­mately 460 patients with re­lapsed and refractory multiple myeloma who have received at least two but no more than three prior ther­a­pies, in­­clud­ing bor­tez­o­mib and an IMiD. Those in­cluded in the study will be ran­dom­ized to receive once-weekly Kyprolis (20 mg/m² on day 1 of cycle 1, 70 mg/m2 on days 8 and 15 of cycle 1 and 70 mg/m² on days 1, 8 and 15 of sub­se­quent cycles) with dexa­meth­a­sone (40 mg) versus twice-weekly Kyprolis (20 mg/m² on days 1 and 2 of cycle 1, 27 mg/m² on days 8, 9, 15 and 16 of cycle 1 and 27 mg/m² on days 1, 2, 8, 9, 15 and 16 of sub­se­quent cycles) with dexa­meth­a­sone (40 mg). The pri­mary end­point of the trial is ORR, defined as the proportion of subjects achieving a best over­all response of partial response, very good partial response, com­plete response or stringent com­plete response based on the Inter­na­tional Myeloma Work­ing Group Uniform Response Criteria. Secondary end­points in­clude PFS, over­all survival and safety and tolerability. The trial is being conducted in approx­i­mately 100 sites world­wide. For more in­­for­ma­tion about this trial, please visit www.clinicaltrials.gov under trial identi­fi­ca­tion number NCT02412878.

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.^1,2 Worldwide, nearly 230,000 people are living with multiple myeloma and approx­i­mately 114,000 new cases are diag­nosed annually.³ In the U.S., there are nearly 96,000 people living with, or in remission from, multiple myeloma. The esti­mated number of new cases of multiple myeloma in 2014 was more than 24,000 and the esti­mated number of deaths was 11,090.⁴ In Europe, approx­i­mately 89,000 people are living with the disease and in 2012 there was an esti­mated 39,000 newly diag­nosed cases and 24,000 deaths.³

Amgen Post-ASCO Summary Webcast

Amgen will hold a post-ASCO summary webcast on Tuesday, June 2 at 1 p.m. CT. Sean E. Harper, M.D., exec­u­tive vice pres­i­dent of Research and Development at Amgen, along with members of Amgen's clin­i­cal devel­op­ment team and clin­i­cal investigators will par­tic­i­pate to discuss data presented at ASCO and Amgen's broader on­col­ogy portfolio of prod­ucts.

Live audio of the event will be simultaneously broadcast over the Internet and will be avail­able to members of the news media, in­­vestors and the general public.

The webcast, as with other selected presentations re­gard­ing devel­op­ments in Amgen's business given by man­agement at certain in­­vestor and medical conferences, can be found on Amgen's website, www.amgen.com, under Investors. Information re­gard­ing presentation times, webcast avail­a­bil­ity and webcast links are noted on Amgen's Investor Relations Events Calendar. The webcast will be archived and avail­able for replay for at least 90 days after the event.

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 also approved for use in Argentina, Israel and Mexico.

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 (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 <1 per­cent 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 per­cent of patients and dis­con­tinu­a­tion of treat­ment with Kyprolis in <1 per­cent of patients.

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

Cases of thrombotic thrombocytopenic purpura/hemolytic uremic syn­drome (TTP/HUS) in­­clud­ing fata out­come have been reported. Treatment with Kyprolis should be dis­con­tinued if signs and symp­toms of TTP/HUS occur.

Cases of posterior reversible encephlophay syn­drome (PRES) have been reported. Treatment with Kyprolis should be dis­con­tinued if PRES is sus­pected.

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.

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 May 31, 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. Amgen may ex­peri­ence dif­fi­culties, delays or unexpected costs and not achieve antic­i­pated cost savings from its recently announced restructuring plan. 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 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. Dimopoulos, M.A. Multiple Myeloma. Annals of Oncology 21 (Supplement 7): vii143–vii150, 2010.
2. National Cancer Institute. SEER Stat Fact Sheets: Myeloma. Available at: http://seer.cancer.gov/statfacts/html/mulmy.html. Accessed May 2015.
3. International Agency for Research on Cancer, GLOBOCAN 2012 database. Available at http://globocan.iarc.fr/. Accessed May 2015.
4. Leukemia & Lymphoma Society. Facts 2014-2015. Available at: http://www.lls.org/content/nationalcontent/resourcecenter/freeeducationmaterials/generalcancer/pdf/facts.pdf. Accessed May 2015.

Source: Amgen.