• Kyprolis, lena­lido­mide, and dexa­meth­a­sone extended median over­all survival in re­lapsed or refractory multiple myeloma patients to 48 months
• Kyprolis is the first and only treat­ment to dem­onstrate over­all survival benefits in two Phase 3 studies in re­lapsed and refractory multiple myeloma

Thousand Oaks, CA (Press Release) – Amgen (NASDAQ: AMGN) today announced that the U.S. Food and Drug Admin­istra­tion (FDA) has approved the supple­mental New Drug Application (sNDA) to add the positive over­all survival (OS) data from the Phase 3 ASPIRE trial to the U.S. Prescribing Information for KYPROLIS® (car­filz­o­mib). Data added to the label showed that KYPROLIS, lena­lido­mide and dexa­meth­a­sone (KRd) sig­nif­i­cantly reduced the risk of death by 21 per­cent and extended over­all survival by 7.9 months versus lena­lido­mide and dexa­meth­a­sone alone (Rd) in patients with re­lapsed or refractory multiple myeloma (median OS 48.3 months for KRd versus 40.4 months for Rd, HR=0.79, 95 per­cent CI, 0.67 – 0.95; two-sided p=0.0091).

"Amgen is focused on ad­vanc­ing treat­ment options that have the poten­tial to transform out­comes for patients," said David M. Reese, M.D., senior vice pres­i­dent of Translational Sciences and Oncology at Amgen. "The ASPIRE trial showed sig­nif­i­cant im­prove­ment in survival in patients with re­lapsed or refractory multiple myeloma who received KYPROLIS as part of a triplet regi­men. With this approval, the U.S. Prescribing Information for KYPROLIS now in­cludes positive over­all survival data from two Phase 3 trials, underscoring the im­por­tant role of pro­te­a­some inhibition in the treat­ment of multiple myeloma."

Full OS results from ASPIRE were published earlier this year in the Journal of Clinical Oncology. The safety data were con­sis­tent with the known safety profile of KYPROLIS. The most common adverse events (greater than or equal to 20 per­cent) in the KYPROLIS arm were diarrhea, anemia, neu­tro­penia, fatigue, upper res­pira­tory tract in­fec­tion, pyrexia, cough, hypokalemia, thrombo­cytopenia, muscle spasms, pneu­monia, nasopharyngitis, nausea, con­sti­pa­tion, insomnia and bronchitis.

Since its approval in 2012, approx­i­mately 80,000 patients world­wide have received KYPROLIS. The KYPROLIS clin­i­cal pro­gram con­tinues to focus on providing treat­ment options for physicians and patients for this frequently relapsing and dif­fi­cult-to-treat blood cancer.

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 dexa­meth­a­sone, versus lena­lido­mide and dexa­meth­a­sone alone, in patients with re­lapsed or refractory 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 OS, 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 one, escalating to 27 mg/m² on days 8, 9, 15 and 16 of cycle one 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, seven days off) and low-dose dexa­meth­a­sone (40 mg per week in four-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 an incurable blood cancer, char­ac­ter­ized by a recurring pattern of remission and relapse.¹ It is a rare and life-threatening disease that accounts for approx­i­mately two per­cent of all cancers.^2,3 In the U.S., there are more than 124,000 people living with, or in remission from, multiple myeloma.² Approximately 30,770 Americans are diag­nosed with multiple myeloma each year and 12,770 patient deaths are reported on an annual basis.²

About KYPROLIS® (car­filz­o­mib)

Proteasomes play an im­por­tant role in cell function and growth by breaking down proteins that are damaged or no longer needed.⁴ KYPROLIS has been shown to block pro­te­a­somes, leading to an excessive build-up of proteins within cells.⁴ 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.^4,5

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

• In com­bi­na­tion with dexa­meth­a­sone or with lena­lido­mide plus dexa­meth­a­sone for the treat­ment of patients with re­lapsed or refractory multiple myeloma who have received one to three lines of ther­apy.
• As a single agent for the treat­ment of patients with re­lapsed or refractory multiple myeloma who have received one or more lines of ther­apy.

KYPROLIS is also approved in Argentina, Australia, Bahrain, Canada, Hong Kong, Israel, Japan, Kuwait, Lebanon, Macao, Mexico, Thailand, Colombia, S. Korea, Qatar, Switzerland, United Arab Emirates, Turkey, Russia, Brazil, India, Oman and the United States. Additional regu­la­tory appli­ca­tions for KYPROLIS are underway and have been submitted to health author­i­ties world­wide.

Important U.S. KYPROLIS® (car­filz­o­mib) Safety Information

Cardiac Toxicities

• New onset or worsening of pre‐existing 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. Some events occurred in patients with normal base­line ventricular function. Death due to cardiac arrest has occurred within one day of KYPROLIS admin­istra­tion.
• Monitor patients for clinical signs or symp­toms of cardiac failure or cardiac ischemia. Evaluate promptly if cardiac toxicity is sus­pected. Withhold KYPROLIS for Grade 3 or 4 cardiac adverse events until recovery, and con­sider whether to restart KYPROLIS at 1 dose level reduction based on a benefit/​risk assess­ment.
• While 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, conduction ab­nor­mal­i­ties, angina, or arrhythmias may be at greater risk for cardiac com­pli­ca­tions and should have a com­pre­hen­sive medical assess­ment (including blood pressure control and fluid man­agement) prior to starting treat­ment with KYPROLIS and remain under close follow‐up.

Acute Renal Failure

• Cases of acute renal failure, including some fatal renal failure events, and renal insufficiency adverse events (including 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. 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. It is recommended to control hyper­tension prior to starting KYPROLIS. 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 for patients being treated with the com­bi­na­tion of KYPROLIS with dexa­meth­a­sone or with lena­lido­mide plus dexa­meth­a­sone. The thrombo­pro­phy­laxis regi­men should be based on an assess­ment of the patient's under­lying risks. Thrombo­pro­phy­laxis is recommended for patients being treated with the com­bi­na­tion of KYPROLIS with dexa­meth­a­sone or with lena­lido­mide plus dexa­meth­a­sone. The thrombo­pro­phy­laxis regi­men should be based on an assess­ment of the patient's under­lying risks.
• Patients using oral con­tra­­cep­tives or a hormonal method of con­tra­cep­tion asso­ci­ated with a risk of thrombosis should con­sider an alter­na­tive method of effective con­tra­cep­tion during treat­ment with KYPROLIS in com­bi­na­tion with dexa­meth­a­sone or lena­lido­mide plus dexa­meth­a­sone.

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. 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.

Hemorrhage

• Fatal or serious cases of hemorrhage have been reported in patients receiving KYPROLIS. Hemorrhagic events have included gastro­in­tes­ti­nal, pul­mo­nary, and intracranial hemorrhage and epistaxis. Promptly evaluate signs and symp­toms of blood loss. Reduce or withhold dose as appropriate.

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 regardless of base­line values. Reduce or withhold dose as appropriate.

Thrombotic Microangiopathy

• Cases of thrombotic microangiopathy, including thrombotic thrombocytopenic purpura/hemolytic uremic syn­drome (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 neuro‐radiological 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.

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

• In a clinical trial of trans­plant‐ineligible patients with newly diagnosed multiple myeloma com­par­ing KYPROLIS, mel­phalan, and pred­ni­sone (KMP) vs bor­tez­o­mib, mel­phalan, and pred­ni­sone (VMP), a higher incidence of serious and fatal adverse events was observed in patients in the KMP arm. KYPROLIS in com­bi­na­tion with mel­phalan and pred­ni­sone is not indicated for trans­plant‐ineligible patients with newly diagnosed multiple myeloma.

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. Males of reproductive potential should be advised to avoid fathering a child while being treated with KYPROLIS. If this drug is used during pregnancy, or if pregnancy occurs while taking this drug, the patient should be apprised of the potential hazard to the fetus.

ADVERSE REACTIONS

• The most common adverse reactions occurring in at least 20% of patients treated with KYPROLIS in the com­bi­na­tion ther­apy trials: anemia, neu­tro­penia, diarrhea, dyspnea, fatigue, thrombo­cytopenia, pyrexia, insomnia, muscle spasm, cough, upper res­pira­tory tract in­fec­tion, hypokalemia.
• The most common side effects occurring in at least 20% of patients receiving KYPROLIS when used alone (monotherapy) in trials are: low red blood cell count, tiredness (fatigue), low platelets, nausea, fever, difficulty breathing, diarrhea, headache, cough, swelling of the lower legs or hands.
• 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.

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 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. 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 reports filed by Amgen, in­­clud­ing our most recent annual report on Form 10-K and any sub­se­quent periodic reports on Form 10-Q and current reports on Form 8-K. Unless other­wise noted, Amgen is providing this in­­for­ma­tion as of the date of this news release and does not under­take any obli­ga­tion to update any forward-looking state­ments con­tained in this document as a result of new in­­for­ma­tion, future events or other­wise.

No forward-looking state­ment can be guar­an­teed and actual results may differ ma­teri­ally from those we project. 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 us to com­plete clin­i­cal trials and obtain regu­la­tory approval for prod­uct market­ing has in the past varied and we ex­pec­t similar variability in the future. Even when clin­i­cal trials are suc­cess­ful, regu­la­tory author­i­ties may question the sufficiency for approval of the trial end­points we have selected. We develop 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 we may have believed at the time of entering into such rela­tion­ship. Also, we or others could identify safety, side effects or manu­fac­tur­ing problems with our prod­ucts, in­­clud­ing our devices, after they are on the market.

Our results may be affected by our ability to suc­cess­fully market both new and existing prod­ucts domestically and inter­na­tionally, clin­i­cal and regu­la­tory devel­op­ments involving current and future prod­ucts, sales growth of recently launched prod­ucts, com­pe­ti­tion from other prod­ucts in­­clud­ing bio­sim­i­lars, dif­fi­culties or delays in manu­fac­tur­ing our prod­ucts and global economic con­di­tions. In addi­tion, sales of our prod­ucts are affected by pricing pressure, political and public scrutiny and 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. Further­more, our research, testing, pricing, market­ing and other operations are subject to extensive reg­u­la­tion by domestic and foreign gov­ern­ment regu­la­tory author­i­ties. Our business may be impacted by gov­ern­ment in­ves­ti­ga­tions, litigation and prod­uct liability claims. In addi­tion, our business may be impacted by the adoption of new tax legislation or exposure to addi­tional tax liabilities. If we fail to meet the compliance obli­ga­tions in the corporate integrity agree­ment be­tween us and the U.S. gov­ern­ment, we could become subject to sig­nif­i­cant sanctions. Further, while we routinely obtain patents for our prod­ucts and tech­nology, the protection offered by our patents and patent appli­ca­tions may be chal­lenged, invalidated or circumvented by our com­pet­i­tors, or we may fail to prevail in present and future intellectual property litigation. We per­form a sub­stan­tial amount of our commercial manu­fac­tur­ing activities at a few key facilities, in­­clud­ing in Puerto Rico, and also depend on third parties for a portion of our manu­fac­tur­ing activities, and limits on supply may constrain sales of certain of our current prod­ucts and prod­uct can­di­date devel­op­ment. In addi­tion, we compete with other com­pa­nies with respect to many of our marketed prod­ucts as well as for the discovery and devel­op­ment of new prod­ucts. Further, some raw ma­teri­als, medical devices and component parts for our prod­ucts are supplied by sole third-party suppliers. Certain of our distributors, customers and payers have sub­stan­tial purchasing leverage in their dealings with us. The discovery of sig­nif­i­cant problems with a prod­uct similar to one of our prod­ucts that implicate an entire class of prod­ucts could have a ma­teri­al adverse effect on sales of the affected prod­ucts and on our business and results of operations. Our efforts to acquire other com­pa­nies or prod­ucts and to integrate the operations of com­pa­nies we have acquired may not be suc­cess­ful. A breakdown, cyberattack or in­­for­ma­tion security breach could compromise the con­fi­den­tiality, integrity and avail­a­bil­ity of our systems and our data. Our stock price is volatile and may be affected by a number of events. Our business per­for­mance could affect or limit the ability of our Board of Directors to declare a dividend or our ability to pay a dividend or repurchase our common stock. We may not be able to access the capital and credit markets on terms that are favorable to us, or at all.

References

1. Jakubowiak A. Management Strategies for Relapsed/Refractory Multiple Myeloma: Current Clinical Perspectives. Seminars in Hematology. 2012; 49(3)(1),S16-S32.. 2012; 49(3)(1),S16-S32.
2. National Cancer Institute. SEER Stat Fact Sheets: Myeloma. Available at: http://seer.cancer.gov/statfacts/html/mulmy.html. Accessed on May 30, 2018.
3. American Cancer Society. About Multiple Myeloma. Available at https://www.cancer.org/content/dam/CRC/PDF/Public/8738.00.pdf. Accessed on April 19, 2018.
4. Moreau P, Richardson PG, Cavo M, et al. Proteasome Inhibitors in Multiple Myeloma: 10 Years Later. Blood. 2012; 120(5):947-959.
5. Kortuem KM and Stewart AK. Carfilzomib. Blood. 2012; 121(6):893-897.. 2012; 121(6):893-897.

Source: Amgen.