Phase 3 Data Showed KYPROLIS and Dexamethasone Reduced the Risk of Death by 21 Percent Versus Velcade® (Bortezomib) and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma

Overall Survival Results Support Use of KYPROLIS in Combination With Dexamethasone as New Standard of Care

THOUSAND OAKS, CA, USA I January 17, 2018 I Amgen (NASDAQ: AMGN) today announced that the U.S. Food and Drug Administration (FDA) has approved the supplemental New Drug Application (sNDA) to add overall survival (OS) data from the Phase 3 head-to-head ENDEAVOR trial to the Prescribing Information for KYPROLIS® (carfilzomib). Data added to the label demonstrated that KYPROLIS and dexamethasone (Kd) reduced the risk of death by 21 percent and increased OS by 7.6 months versus Velcade® (bortezomib) and dexamethasone (Vd) in patients with relapsed or refractory multiple myeloma (median OS 47.6 months for Kd versus 40.0 months for Vd, HR=0.79; p=0.01).

“Overall survival is generally considered to be the gold standard of endpoints because it clearly demonstrates a drug’s value in extending a patient’s life, 1,2” said David M. Reese, M.D., senior vice president of Translational Sciences and Oncology at Amgen. “Blood cancer therapies approved by the FDA between 2003 and 2013 only improved overall survival by an average of 2.61 months.3 KYPROLIS and dexamethasone improved overall survival by 7.6 months, underscoring that this regimen is a significant advancement and should be considered a standard of care for patients with relapsed or refractory multiple myeloma.”

The National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (NCCN Guidelines®) list Kd as the only preferred doublet regimen at relapse for multiple myeloma. Full OS results from the ENDEAVOR trial were published earlier this year in The Lancet Oncology.

Adverse events observed in this updated analysis were consistent with those previously reported for ENDEAVOR. The most common adverse events (greater than or equal to 20 percent) in the KYPROLIS arm were anemia, diarrhea, pyrexia, dyspnea, fatigue, hypertension, cough, insomnia, upper respiratory tract infection, peripheral edema, nausea, bronchitis, asthenia, back pain, thrombocytopenia and headache.

Since its approval in 2012, more than 50,000 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 cancer. KYPROLIS is available for patients whose myeloma has relapsed or become resistant to another treatment and continues to be studied in a range of combinations and patient populations.

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 progression-free survival, 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 of 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.4 It is a rare and life-threatening disease that accounts for approximately one percent of all cancers.5,6 In the U.S., there are more than 118,000 people living with, or in remission from, multiple myeloma.7 Approximately 30,280 Americans are diagnosed with multiple myeloma each year and 12,590 patient deaths are reported on an annual basis.7

About KYPROLIS® (carfilzomib) 
Proteasomes play an important role in cell function and growth by breaking down proteins that are damaged or no longer needed.8 KYPROLIS has been shown to block proteasomes, leading to an excessive build-up of proteins within cells.8 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.8,9

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, 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.

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.

References

  1. Genentech. Manag Care. 2016; 1(suppl):1-12.
  2. Pazdur, R. FDA Voice. https://blogs.fda.gov/fdavoice/index.php/2017/06/in-cancer-treatment-theres-more-than-one-way-to-measure-patient-benefit. Accessed November 5, 2017.  
  3. Salas-Vega S, et al. Assessment of Overall Survival, Quality of Life, and Safety Benefits Associated With New Cancer medicines. JAMA Oncol. 2017;3:382-390
  4. Jakubowiak A. Management Strategies for Relapsed/Refractory Multiple Myeloma: Current Clinical Perspectives. Seminars in Hematology. 2012; 49(3)(1),S16-S32.
  5. 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%A0. Accessed on Dec. 21, 2017.
  6. American Cancer Society. About Multiple Myeloma. Available at https://www.cancer.org/content/dam/CRC/PDF/Public/8738.00.pdf. Accessed on Dec. 21, 2017.
  7. National Cancer Institute. SEER Stat Fact Sheets: Myeloma. Available at: http://seer.cancer.gov/statfacts/html/mulmy.html. Accessed on Dec. 21, 2017.
  8. Moreau P, Richardson PG, Cavo M, et al. Proteasome Inhibitors in Multiple Myeloma: 10 Years Later. Blood. 2012; 120(5):947-959.
  9. Kortuem KM and Stewart AK. Carfilzomib. Blood. 2012; 121(6):893-897.

SOURCE: Amgen