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KYPROLIS® (carfilzomib) Extended Overall Survival In Patients With Relapsed Or Refractory Multiple Myeloma In Phase 3 ASPIRE Trial


THOUSAND OAKS, Calif., Dec. 11, 2017 /PRNewswire/ -- Amgen (NASDAQ: AMGN) today announced new results showing the positive overall survival (OS) findings from the final analysis of the Phase 3 ASPIRE trial. The study met the key secondary endpoint of OS, demonstrating that the addition of KYPROLIS® (carfilzomib) to lenalidomide and dexamethasone (KRd) reduced the risk of death by 21 percent versus lenalidomide and dexamethasone alone (Rd) and extended survival by 7.9 months 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; p = 0.0045). These results were presented today during an oral presentation at the 59th American Society of Hematology (ASH) Annual Meeting & Exposition in Atlanta (ASH abstract #743).

"While significant advances have recently been made in treating relapsed or refractory multiple myeloma, most reported clinical trials have focused on how long a new treatment helps prevent recurrence of disease rather than on survival," said Keith Stewart, M.B., Ch.B.,  Mayo Clinic in Arizona and principal investigator of the ASPIRE trial. "Results from the ASPIRE trial are among the first  to show a significant overall survival advantage resulting from adding carfilzomib to lenalidomide and dexamethasone treatment in patients with relapsed or refractory multiple myeloma.  The data support the early use of carfilzomib as an effective therapy at first relapse, regardless of prior treatment with Velcade or transplant."

"KYPROLIS-based regimens are the first and only to demonstrate superior overall survival versus today's standard of care in two Phase 3 studies and are resetting survival expectations for relapsed or refractory multiple myeloma patients," said David Reese, M.D., senior vice president of Translational Sciences and Oncology at Amgen. "We are pleased with the KYPROLIS overall survival data presented at ASH this year as the results underscore our commitment to developing innovative treatment options to help cancer patients live longer."

The final analysis of ASPIRE included subgroup analyses by prior lines of therapy, prior Velcade exposure at first relapse, and prior transplant at first relapse. Among these three groups, there was an 18 to 29 percent reduction in the risk of death for KRd versus Rd, consistent with findings in the overall population. Median OS was 11.4 months longer for KRd versus Rd in patients who had received one prior line of therapy (47.3 versus 35.9 months [HR = 0.81, 95 percent CI, 0.62 ? 1.06]) and 6.5 months longer for patients with two or more prior lines (48.8 versus 42.3 months [HR = 0.79, 95 percent CI, 0.62 ? 0.99]).

Notably the maximum OS improvement of 11 months was observed for patients at first relapse. This OS analysis supports the early use of KYPROLIS as effective therapy at first relapse, regardless of prior Velcade exposure or transplant. Patients treated with KRd reported improved global health status, with higher Global Health Status/Quality of Life (QoL) scores compared with Rd over 18 cycles of treatment (1?sided p?value = 0.0001) measured with the EORTC QLQ?C30, an instrument validated in multiple myeloma.

Overall survival by Revised International Staging System (R-ISS) stage was also assessed. For R-ISS stage I (KRd, n = 42; Rd, n = 46), median OS was not reached for KRd and was 58 months for Rd (HR = 0.49, 95 percent CI, 0.26 ? 0.92). For patients with R-ISS stage II (KRd, n = 194; Rd, n = 195), median OS was 45.4 months for KRd and 41.2 months for Rd (4.2 months; HR = 0.86, 95 percent CI, 0.68 ? 1.10). For the small number of patients with R-ISS stage III (KRd, n = 37; Rd, n = 47), median OS was 23.3 months for KRd and 18.8 months for Rd (4.5 months; HR = 1.05, 95 percent CI, 0.66 ? 1.68).

The safety data from ASPIRE was 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.

Overall survival results from the Phase 3 ENDEAVOR head-to-head study of KYPROLIS plus dexamethasone (Kd) versus Velcade plus dexamethasone were also presented at ASH and showed that Kd was superior in extending survival across a variety of sub-group analyses of relapsed or refractory multiple myeloma patients, including age, prior line of therapy and previous exposure to Velcade (ASH abstract #1885, ASH abstract #1850).

The KRd and Kd regimens used in these trials are currently approved in the U.S., European Union and other countries based on primary analyses of progression-free survival (PFS) in the ASPIRE and ENDEAVOR studies, respectively. The KYPROLIS dosing used for ASPIRE (27 mg/m2; 10-minute infusion) and ENDEAVOR (56 mg/m2; 30-minute infusion) were optimized for each treatment regimen and are the currently approved doses for the KRd and Kd regimens, respectively.1

Based on the ASPIRE results, Amgen has submitted a supplemental New Drug Application to the U.S. Food and Drug Administration to include the OS data from ASPIRE in the product information for KYPROLIS.

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 PFS, 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, 7 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.

For the overall study population, treatment discontinuation due to an adverse event occurred in 19.9 percent of patients treated with KRd and 21 percent of patients receiving Rd. Fatal adverse events were reported in 11.5 percent of KRd-treated patients and 10.5 percent of patients treated with Rd. Grade ?3 adverse event rates were 87 percent for KRd and 83 percent for Rd. Selected grade ?3 adverse events of interest (grouped terms; KRd vs Rd) included acute renal failure (3.8 percent versus 3.3 percent), cardiac failure (4.3 percent versus 2.1 percent), ischemic heart disease (3.8 percent versus 2.3 percent), hypertension (6.4 percent versus 2.3 percent), and hematopoietic thrombocytopenia (20.2 percent versus 14.9 percent).

About ENDEAVOR 
The randomized ENDEAVOR (RandomizEd, OpeN Label, Phase 3 Study of Carfilzomib Plus DExamethAsone Vs Bortezomib Plus DexamethasOne in Patients With Relapsed Multiple Myeloma) trial of 929 patients evaluated KYPROLIS in combination with low-dose dexamethasone, versus Velcade with low-dose dexamethasone in relapsed or refractory patients who previously received at least one, but not more than three prior therapeutic regimens. The primary endpoint of the trial was PFS, defined as the time from treatment initiation to disease progression or death. The primary analysis was published in The Lancet Oncology and is described in the Prescribing Information.

Patients received treatment until progression with KYPROLIS as a 30-minute infusion on days 1, 2, 8, 9, 15 and 16 of 28 day treatment cycles, along with low-dose dexamethasone (20 mg). For cycle one only, KYPROLIS was administered at 20 mg/mon days 1 and 2, and if tolerated was escalated to 56 mg/m2 from day 8 cycle one onwards. Patients who received Velcade (1.3 mg/m2) with low-dose dexamethasone (20 mg) were treated with Velcade administered subcutaneously or intravenously at the discretion of the investigator and in accordance with regional regulatory approval of Velcade. More than 75 percent of the patients in the control arm received Velcade subcutaneously. This study was conducted at 235 sites worldwide. For information about this trial, please visit www.clinicaltrials.gov under trial identification number NCT01568866.

About Multiple Myeloma
Multiple myeloma is an incurable blood cancer, characterized by a recurring pattern of remission and relapse.2 It is a rare and life-threatening disease that accounts for approximately one percent of all cancers. 3,4 Worldwide, approximately 114,000 people are diagnosed with multiple myeloma each year and 80,000 patient deaths are reported on an annual basis.3

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:

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

IMPORTANT SAFETY INFORMATION

Cardiac Toxicities

Acute Renal Failure

Tumor Lysis Syndrome

Pulmonary Toxicity

Pulmonary Hypertension

Dyspnea

Hypertension

Venous Thrombosis

Infusion Reactions

Hemorrhage

Thrombocytopenia

Hepatic Toxicity and Hepatic Failure

Thrombotic Microangiopathy

Posterior Reversible Encephalopathy Syndrome (PRES)

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

Embryo-fetal Toxicity

ADVERSE REACTIONS

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 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 manufacturing 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. 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.

CONTACT: Amgen, Thousand Oaks
Kristen Davis, 805-447-3008 (Media)
Kristen Neese, 805-313-8267 (Media)
Arvind Sood, 805-447-1060 (Investors)

Amgen Logo. (PRNewsFoto/Amgen) (PRNewsFoto/)

References

  1. Jakubowiak A. Evolution of Carfilzomib Dose and Schedule in Patients With Multiple Myeloma: A Historical Overview. Cancer Treatment Review. 2014; 40(6):781-790.
  2. Jakubowiak A. Management Strategies for Relapsed/Refractory Multiple Myeloma: Current Clinical Perspectives. Seminars in Hematology. 2012; 49(3)(1),S16-S32.
  3. GLOBOCAN 2012. Global Prevalence and Incidence. Available at: http://globocan.iarc.fr/old/summary_table_pop_prev.asp?selection=224900&title=World&sex=0&window=1&sort=0&submit=%C2%A0Execute%C2%A0http://globocan.iarc.fr/old/summary_table_pop_prev.asp?selection=224900&title=World&sex=0&window=1&sort=0&submit=%C2%A0Execute%C2%A0. Accessed on Nov. 3, 2017.
  4. American Cancer Society. About Multiple Myeloma. Available at https://www.cancer.org/content/dam/CRC/PDF/Public/8738.00.pdf. Accessed on Nov. 3, 2017.
  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):893-897.

 

SOURCE Amgen


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