Initial Phase 3 Registrational Study Planned in Relapsed or Refractory Multiple Myeloma Patients

Thousand Oaks, CA (Press Release) – Amgen (NASDAQ: AMGN) today announced a col­lab­o­ration with Janssen Biotech, Inc. to eval­u­ate the com­bi­na­tion of Amgen's KYPROLIS® (car­filz­o­mib) and Janssen's DARZALEX® (dara­tu­mu­mab) in multiple clin­i­cal studies in patients with multiple myeloma. Under the terms of the agree­ment, the com­pa­nies may elect to supply drug only or supply drug and share devel­op­ment costs on a study-by-study basis.

The first study ini­ti­ated as part of this agree­ment is a Phase 3 registrational trial eval­u­ating KYPROLIS in com­bi­na­tion with DARZALEX and dexa­meth­a­sone com­pared to KYPROLIS and dexa­meth­a­sone alone in patients with multiple myeloma who have had one, two or three prior lines of ther­apy. The rationale for com­bining these agents is that they have dem­onstrated sub­stan­tial activity in multiple myeloma, with distinct and com­ple­men­tary mech­a­nisms of action. The study is antic­i­pated to start enrolling patients in April 2017.

"Given the relapsing nature of multiple myeloma, several options are needed to attack the disease dif­fer­en­tly and keep patients in remission as long as possible," said Sean E. Harper, M.D., exec­u­tive vice pres­i­dent of Research and Development at Amgen. "We are excited to col­lab­o­rate with Janssen to eval­u­ate the poten­tial of com­bining KYPROLIS, a powerful pro­te­a­some inhibitor, with DARZALEX, the first human anti-CD38 mono­clonal anti­body for the treat­ment of multiple myeloma in the re­lapsed setting."

As part of an earlier and separate agree­ment, Amgen is also supplying KYPROLIS for Janssen's open-label Phase 1b study. The com­bi­na­tion of DARZALEX and KYPROLIS is being in­ves­ti­gated in this Phase 1b study in two cohorts. One cohort in­cludes DARZALEX in com­bi­na­tion with KYPROLIS and dexa­meth­a­sone in patients who pre­vi­ously received one to three prior lines of ther­apy. The second cohort in­cludes DARZALEX in com­bi­na­tion with KYPROLIS, REVLIMID® (lena­lido­mide) and dexa­meth­a­sone in subjects with newly diag­nosed multiple myeloma, re­gard­less of trans­plan­ta­tion eligibility. Both Phase 1 cohorts are fully enrolled.

About the Phase 3 Study Design

The proposed study design is a Phase 3, open-label, ran­domized study in multiple myeloma patients with one, two or three prior lines of ther­apy. Patients will be treated to pro­gres­sion. In the first arm, patients will receive KYPROLIS twice weekly at 56 mg/m² and dexa­meth­a­sone in com­bi­na­tion with DARZALEX (KdD). In the second arm (control), patients will receive KYPROLIS twice weekly at 56 mg/m² and dexa­meth­a­sone (Kd). The pri­mary end­point is pro­gres­sion-free survival (PFS) and the key sec­ond­ary end­points are over­all response rate, minimal residual disease and over­all survival.

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 very aggressive disease that accounts for approx­i­mately one per­cent of all cancers.^2,3 In the U.S., there are nearly 95,000 people living with, or in remission from, multiple myeloma.⁴ Approx­i­mately 30,330 Americans are diag­nosed with multiple myeloma each year and 12,650 patient deaths are reported on an annual basis.⁴

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 KYPROLIS® (car­filz­o­mib)

Proteasomes play an im­por­tant role in cell function and growth by breaking down proteins that are damaged or no longer needed.⁵ KYPROLIS has been shown to block pro­te­a­somes, leading to an excessive build-up of proteins within cells.⁵ 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.^5,6

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, Israel, Kuwait, Mexico, Thailand, Colombia, Korea, Canada, Switzerland, Russia, Brazil and the European Union. Additional regu­la­tory appli­ca­tions for KYPROLIS are underway and have been submitted to health author­i­ties world­wide.

For more U.S. in­­for­ma­tion, please visit www.kyprolis.com.

IMPORTANT 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 and fluid management) prior to starting treatment with KYPROLIS and remain under close follow-up.

Acute Renal Failure

• Cases of acute renal failure 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. 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.
• 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.

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.

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 adverse reactions occurring in at least 20% of patients treated with KYPROLIS in monotherapy trials: anemia, fatigue, thrombocytopenia, nausea, pyrexia, dyspnea, diarrhea, headache, cough, edema peripheral.

Please see full pre­scrib­ing in­­for­ma­tion 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 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 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 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. We or others could identify safety, side effects or manu­fac­tur­ing problems with our prod­ucts after they are on the mar­ket. 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 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. 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. We may not be able to access the capital and credit mar­kets on terms that are favorable to us, or at all. We are in­creas­ingly dependent on in­­for­ma­tion tech­nology sys­tems, infrastructure and data se­cu­ri­ty. 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.

The scientific in­­for­ma­tion discussed in this news release relating to new indi­ca­tions for our prod­ucts is pre­lim­i­nary and investigative and is not part of the labeling approved by the U.S. Food and Drug Admin­is­tra­tion or the European Medicines Agency 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.

DARZALEX® (dara­tu­mu­mab) is a registered trademark of Janssen Biotech, Inc.
REVLIMID® (lena­lido­mide) is a registered trademark of Celgene Corpo­ra­tion.

References

1. Jakubowiak A. Management Strategies for Relapsed/Refractory Multiple Myeloma: Current Clinical Perspectives. Seminars in Hematology. 2012; 49(3)(1),S16-S32.
2. GLOBOCAN 2012, Global Prevalence and Incidence, available at http://globocan.iarc.fr/old/summary_table_pop_prev.aspselection=224900&title=World&sex=0&window=1&sort=0&submit=%C2%A0Execute%C2%A0, accessed on March 9, 2015.
3. American Cancer Society. Multiple myeloma. http://www.cancer.org/acs/groups/cid/documents/webcontent/003121-pdf.pdf. Accessed on: October 30, 2015.
4. National Cancer Institute. SEER Stat Fact Sheets: Myeloma. Available at: http://seer.cancer.gov/statfacts/html/mulmy.html. Accessed on August 5, 2016.
5. Moreau P, Richardson PG, Cavo M, et al. Proteasome Inhibitors in Multiple Myeloma: 10 Years Later. Blood. 2012; 120(5):947-959.
6. Kortuem KM and Stewart AK. Carfilzomib. Blood. 2012; 121(6-897.

Source: Amgen.