Study met Primary Endpoint of Non-Inferiority Versus Zoledronic Acid in Delaying Bone Complications Known as Skeletal-Related Events

Thousand Oaks, CA (Press Release) – Amgen (NASDAQ: AMGN) today announced that a Phase 3 study eval­u­ating XGEVA® (denosumab) versus zoledronic acid met the pri­mary end­point of non-inferiority (hazard ratio = 0.98, 95 per­cent CI, 0.85 - 1.14) in delaying the time to first on-study skeletal-related event (SRE) in patients with multiple myeloma. The sec­ond­ary end­points of superiority in delaying time to first SRE and delaying time to first-and-subsequent SRE were not met. The hazard ratio of XGEVA versus zoledronic acid for over­all survival was 0.90 (95 per­cent CI, 0.70 - 1.16).

Adverse events observed in patients treated with XGEVA were generally con­sis­tent with the known safety profile of XGEVA. The most common adverse events (greater than 25 per­cent) in the XGEVA arm of the study were diarrhea and nausea.

"Bone com­pli­ca­tions like fracture, spinal cord compression and radiation or surgery to bone are dev­as­tat­ing for multiple myeloma patients. Many of these patients suffer from renal im­pair­ment, which has limited their treat­ment options," said Sean E. Harper, M.D., exec­u­tive vice pres­i­dent of Research and Development at Amgen. "XGEVA's unique mech­a­nism of action has the poten­tial to prevent bone com­pli­ca­tions in multiple myeloma patients re­gard­less of their renal status, fulfilling an im­por­tant unmet medical need."

Detailed results will be submitted to a future medical conference and for publication. The Company plans to submit these data to regu­la­tory author­i­ties.

About '482 Study (NCT01345019)

The '482 study was an inter­na­tional, ran­domized, double-blind, multi­center trial of XGEVA compared with zoledronic acid in the prevention of bone com­pli­ca­tions in patients with newly diag­nosed multiple myeloma. In the study, a total of 1,718 patients (859 on each arm) were ran­domized to receive either sub­cu­tane­ous XGEVA 120 mg and in­tra­venous placebo every four weeks, or in­tra­venous zoledronic acid 4 mg (adjusted for renal function) and sub­cu­tane­ous placebo every four weeks. The pri­mary end­point of the study was non-inferiority of XGEVA versus zoledronic acid with respect to time to first on-study SRE (fracture, radiation to bone, surgery to bone or spinal cord compression). Secondary end­points in­cluded superiority of XGEVA versus zoledronic acid with respect to time to first on-study SRE and first-and-subsequent on-study SRE and over­all survival.The safety and tolerability of XGEVA were also compared with zoledronic acid.

About Multiple Myeloma and Bone Complications

Multiple myeloma is the second most common hema­to­logic cancer, and it develops in plasma cells located in the bone marrow.^1,2 Each year an esti­mated 114,000 new cases of multiple myeloma are diag­nosed world­wide, resulting in more than 80,000 deaths per year.²

Bone lesions frequently accompany multiple myeloma and can in­­crease the risk of bone com­pli­ca­tions.^3,4 Approximately 75 per­cent of multiple myeloma patients are treated for the prevention of bone com­pli­ca­tions.⁵ Preventing bone com­pli­ca­tions is an im­por­tant aspect of caring for patients with multiple myeloma, because these events can cause sig­nif­i­cant morbidity.⁶

About XGEVA® (denosumab)

XGEVA targets the RANK ligand path­way to prevent the for­ma­tion, function and survival of osteoclasts, which break down bone. XGEVA is indicated for the prevention of SREs in patients with bone metastases from solid tumors and for treat­ment of adults and skeletally mature adolescents with giant cell tumor of bone that is un­re­sectable or where surgical resection is likely to result in severe morbidity. XGEVA is also in­di­cated in the U.S. for the treat­ment of hyper­cal­cemia of malig­nan­cy refractory to bis­phos­phonate ther­apy. XGEVA is not in­di­cated for the pre­vention of skeletal-related events in patients with multiple myeloma.

U.S. Important Safety Information

Hypocalcemia

Pre-existing hypo­cal­cemia must be corrected prior to initiating ther­apy with XGEVA. XGEVA can cause severe symp­tomatic hypo­cal­cemia, and fatal cases have been reported. Monitor cal­cium levels, especially in the first weeks of initiating ther­apy, and admin­ister cal­cium, magnesium, and vitamin D as nec­es­sary. Monitor levels more frequently when XGEVA is admin­istered with other drugs that can also lower cal­cium levels. Advise patients to contact a health­care professional for symp­toms of hypo­cal­cemia.

An in­­creased risk of hypo­cal­cemia has been observed in clin­i­cal trials of patients with in­creas­ing renal dysfunction, most commonly with severe dysfunction (creatinine clearance less than 30 mL/minute and/or on dialysis), and with inadequate/no cal­cium supple­mentation. Monitor cal­cium levels and cal­cium and vitamin D intake.

Hypersensitivity

XGEVA is con­tra­in­di­cated in patients with known clin­i­cally sig­nif­i­cant hypersensitivity to XGEVA, in­­clud­ing anaphylaxis that has been reported with use of XGEVA. If an anaphylactic or other clin­i­cally sig­nif­i­cant allergic reac­tion occurs, ini­ti­ate appro­pri­ate ther­apy and dis­con­tinue XGEVA ther­apy perma­nently.

Drug Products with Same Active Ingredient

Patients receiving XGEVA should not take Prolia® (denosumab).

Osteonecrosis of the Jaw

Osteonecrosis of the jaw (ONJ) has occurred in patients receiving XGEVA, manifesting as jaw pain, osteo­myelitis, osteitis, bone erosion, tooth or periodontal in­fec­tion, toothache, gingival ulceration, or gingival erosion. Persistent pain or slow heal­ing of the mouth or jaw after dental surgery may also be mani­fest­a­tions of ONJ. In clin­i­cal trials in patients with osseous metastasis, the incidence of ONJ was higher with longer dura­tion of exposure.

Patients with a history of tooth extraction, poor oral hygiene, or use of a dental appliance are at a greater risk to develop ONJ. Other risk factors for the devel­op­ment of ONJ in­clude immuno­sup­pres­sive ther­apy, treat­ment with angiogenesis inhibitors, systemic corticosteroid, diabetes, and gingival in­fec­tions.

Perform an oral examination and appro­pri­ate preventive dentistry prior to the initiation of XGEVA and peri­od­ically during XGEVA ther­apy. Advise patients re­gard­ing oral hygiene practices. Avoid in­­vasive dental pro­cedures during treat­ment with XGEVA. Consider temporarily interrupting XGEVA ther­apy if an in­­vasive dental procedure must be per­formed.

Patients who are sus­pected of having or who develop ONJ while on XGEVA should receive care by a dentist or an oral surgeon. In these patients, extensive dental surgery to treat ONJ may exacerbate the con­di­tion.

Atypical Subtrochanteric and Diaphyseal Femoral Fracture

Atypical femoral fracture has been reported with XGEVA. These fractures can occur any­where in the femoral shaft from just below the lesser trochanter to above the supracondylar flare and are transverse or short oblique in orientation without evi­dence of comminution.

Atypical femoral fractures most commonly occur with minimal or no trauma to the affected area. They may be bilateral and many patients report prodromal pain in the affected area, usually presenting as dull, aching thigh pain, weeks to months before a com­plete fracture occurs. A number of reports note that patients were also receiving treat­ment with glucocorticoids (e.g. pred­ni­sone) at the time of fracture. During XGEVA treat­ment, patients should be advised to report new or unusual thigh, hip, or groin pain. Patient presenting with an atypical femur fracture should also be assessed for symp­toms and signs of fracture in the contra­lateral limb. Interruption of XGEVA ther­apy should be con­sidered, pending a risk/benefit assess­ment, on an individual basis.

Embryo-Fetal Toxicity

XGEVA can cause fetal harm when admin­istered to a pregnant woman. Based on findings in animals, XGEVA is ex­pec­ted to result in adverse reproductive effects. Advise females of reproductive poten­tial to use highly effective con­tra­cep­tion during ther­apy, and for at least five months after the last dose of XGEVA. Apprise the patient of the poten­tial hazard to a fetus if XGEVA is used during pregnancy or if the patient becomes pregnant while patients are exposed to XGEVA.

Adverse Reactions

The most common adverse reac­tions in patients receiving XGEVA with bone metastasis from solid tumors were fatigue/asthenia, hypophosphatemia, and nausea. The most common serious adverse reac­tion was dyspnea.

The most common adverse reac­tions in patients receiving XGEVA for giant cell tumor of bone were ar­thral­gia, headache, nausea, back pain, fatigue, and pain in extremity. The most common serious adverse reac­tions were osteo­necrosis of the jaw and osteo­myelitis. The most common adverse reac­tions resulting in dis­con­tinua­tion of XGEVA were osteo­necrosis of the jaw and tooth abscess or tooth in­fec­tion.

The most common adverse reac­tions in patients receiving XGEVA for hypercalcemia of malig­nan­cy were nausea, dyspnea, de­creased appetite, headache, periph­eral edema, vomiting, anemia, con­sti­pa­tion, and diarrhea.

Denosumab is also marketed as Prolia® in other indi­ca­tions.

Please visit www.amgen.com or www.xgeva.com for Full U.S. Prescribing Information.

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 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 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. Multiple Myeloma Research Foundation. What is Multiple Myeloma? Accessed Oct. 7, 2016.
2. Globocan 2012: Estimated Cancer Incidence, Mortality and Prevalence in 2012. http://globocan.iarc.fr/Pages/fact_sheets_population.aspx. Accessed Oct. 7, 2016.
3. Roodman GD. Pathogenesis of myeloma bone disease. Leukemia. 2009;23(3):435–441.
4. Terpos E, et al. International Myeloma Working Group recommendations for the treatment of multiple myeloma-related bone disease. J Clin Oncol. 2013;31(18):2347-57.
5. Amgen data on file.
6. Drake MT. Bone disease in multiple myeloma. Oncology (Williston Park). 2009;23(14 Suppl 5):28-32.

Source: Amgen.