THOUSAND OAKS, Calif. and SOUTH SAN FRANCISCO, Calif., Feb. 26, 2015 /PRNewswire/ -- Amgen (NASDAQ: AMGN) and its subsidiary Onyx Pharmaceuticals, Inc., today announced that the European Medicines Agency (EMA) has accepted the Marketing Authorization Application (MAA) of Kyprolis® (carfilzomib) for Injection for the treatment of patients with relapsed multiple myeloma who have received at least one prior therapy. The MAA has been granted accelerated assessment by the EMA.
Kyprolis is a proteasome inhibitor, one of the classes of drugs used to treat multiple myeloma, an incurable blood cancer affecting approximately 89,000 people in Europe.1 Nearly all patients with the disease experience periods of remission, followed by relapses and eventually their disease becomes resistant to treatment.
"Achieving deep and durable responses for patients with relapsed multiple myeloma is critical towards extending the time they live without their disease progressing," said Pablo J. Cagnoni, M.D., president, Onyx Pharmaceuticals, Inc. "We look forward to working with European regulators to potentially make this important medication available."
The MAA includes data from the Phase 3 ASPIRE (CArfilzomib, Lenalidomide, and DexamethaSone versus Lenalidomide and Dexamethasone for the treatment of PatIents with Relapsed Multiple MyEloma) trial as well as other relevant data.
Kyprolis previously received orphan drug designation by the EMA in the European Union (EU). Orphan designation is granted for medicines intended for the treatment, prevention or diagnosis of a disease that is life threatening and has a prevalence in the EU of no more than five in 10,000. The intended medicine must aim to provide significant benefit to those affected by the condition.2
Kyprolis was granted accelerated approval by the U.S. Food and Drug Administration (FDA) in July 2012. Kyprolis is also approved for use in Argentina, Israel and Mexico.3-5
About Multiple Myeloma
Multiple myeloma is the second most common hematologic cancer and results from an abnormality of plasma cells, usually in the bone marrow.6 Worldwide, nearly 230,000 people are living with multiple myeloma.1 In 2012, approximately 114,000 new cases were diagnosed and 80,000 people died.7 In Europe, approximately 89,000 people are living with multiple myeloma. Approximately 39,000 new cases were diagnosed and 24,000 people died in 2012.1 In the U.S., approximately 83,000 people were living with multiple myeloma in 2011. The estimated number of new cases in 2014 was 24,000 and the estimated number of deaths was 11,000.8
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 low-dose dexamethasone, versus lenalidomide and low-dose dexamethasone alone, in patients with relapsed 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 overall survival, 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 1 only, escalating to 27 mg/m2 on days 8, 9, 15 and 16 of cycle 1 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 4 week cycles), versus lenalidomide and low-dose dexamethasone alone. The study randomized 792 patients at sites in North America, Europe and Israel.
The ASPIRE data were presented at the 56th Annual Meeting of the American Society of Hematology in December 2014 and published in the New England Journal of Medicine.
Onyx Pharmaceuticals received Scientific Advice from the EMA on the design and planned analysis of the ASPIRE trial and it was conducted under a Special Protocol Assessment (SPA) from the FDA.
About Kyprolis® (carfilzomib) for Injection
On July 20, 2012, the U.S. FDA granted accelerated approval of Kyprolis® (carfilzomib) for Injection for the treatment of patients with multiple myeloma who have received at least two prior therapies including bortezomib and an immunomodulatory agent (IMiD) and have demonstrated disease progression on or within 60 days of completion of the last therapy. Approval was based on response rate. Clinical benefit, such as improvement in survival or symptoms, has not been verified.
Kyprolis is a product of Onyx Pharmaceuticals, Inc. Onyx Pharmaceuticals is a subsidiary of Amgen and holds development and commercialization rights to Kyprolis globally, excluding Japan. For more information about Kyprolis, visit www.kyprolis.com.
Important Safety Information Regarding Kyprolis® (carfilzomib) for Injection U.S. Indication
This safety information is specific to the current U.S. approved indication, which is based on Phase 2 studies.
Safety data have been evaluated in 526 patients with relapsed and/or refractory multiple myeloma who received single-agent Kyprolis. There were 37 deaths in the Phase 2 studies, or 7 percent of patients. The most common causes of death, other than disease progression, were cardiac events (5 patients), end-organ failure (4 patients) and infection (4 patients). Important warnings and precautions include cardiac arrest, congestive heart failure, myocardial ischemia, pulmonary hypertension, pulmonary complications, infusion reactions, tumor lysis syndrome, thrombocytopenia, hepatic toxicity and embryo-fetal toxicity.
Death due to cardiac arrest has occurred within a day of Kyprolis administration. Patients with New York Heart Association Class III and IV heart failure, myocardial infarction in the preceding 6 months and conduction abnormalities uncontrolled by medications were not eligible for the clinical trials. These patients may be at greater risk for cardiac complications.
Pulmonary arterial hypertension (PAH) was reported in 2 percent of patients treated with Kyprolis and was Grade 3 or greater in less than 1 percent of patients. Dyspnea was reported in 35 percent of patients enrolled in clinical trials. Grade 3 dyspnea occurred in 5 percent; no Grade 4 events and 1 death (Grade 5) was reported.
Infusion reactions, characterized by a spectrum of systemic symptoms including fever, chills, arthralgia, myalgia, facial flushing, facial edema, vomiting, weakness, shortness of breath, hypotension, syncope, chest tightness, or angina can occur immediately following or up to 24 hours after administration of Kyprolis. Administration of dexamethasone prior to Kyprolis reduces the incidence and severity of reactions. Tumor lysis syndrome (TLS) occurred following Kyprolis administration in <1 percent of patients. Patients with multiple myeloma and a high tumor burden should be considered to be at greater risk for TLS.
Thrombocytopenia following Kyprolis administration resulted in a dose reduction in 1 percent of patients and discontinuation of treatment with Kyprolis in <1 percent of patients.
Cases of hepatic failure, including fatal cases, have been reported (<1 percent). Kyprolis can cause elevations of serum transaminases and bilirubin.
There are no adequate and well-controlled studies in pregnant women using Kyprolis. Females of reproductive potential should be advised to avoid becoming pregnant while being treated with Kyprolis.
The most common serious adverse reactions were pneumonia, acute renal failure, pyrexia and congestive heart failure. The most common adverse reactions (incidence of 30 percent or greater) observed in clinical trials of patients with multiple myeloma were fatigue, anemia, nausea, thrombocytopenia, dyspnea, diarrhea and pyrexia. Serious adverse reactions were reported in 45 percent of patients.
Full prescribing information is available at www.kyprolis.com.
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About Onyx Pharmaceuticals, Inc.
Based in South San Francisco, California, Onyx Pharmaceuticals, Inc., an Amgen subsidiary, is a global biopharmaceutical company engaged in the development and commercialization of innovative therapies for improving the lives of people with cancer. The company is focused on developing novel medicines that target key molecular pathways. For more information about Onyx, visit the company's website at www.onyx.com. Onyx Pharmaceuticals is on Twitter. Sign up to follow our Twitter feed @OnyxPharm at http://twitter.com/OnyxPharm.
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Lindsay Treadway, 650-266-5346 (Onyx media)
Cuyler Mayer, 805-447-6332 (Amgen media)
Arvind Sood, 805-447-1060 (investors)
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2 European Medicines Agency. Orphan designation criteria. Available at:
http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/general_content_000029.jsp. Accessed January 2015.
3 Varifarna Press Release. http://www.varifarma.com.ar/noticias/5/90/Lanzamiento-Kyprolis-Carfilzomib-en-Argentina/. Accessed January 2015.
4 Israel Drug Registry. http://www.old.health.gov.il/units/pharmacy/trufot/PerutTrufa.asp?Reg_Number=151%2021%2033948%20 00&NewTruf=2&safa=. Accessed January 2015
5 Amgen Press Release. Available at: http://www.lasalud.mx/permalink/13981.html. Accessed January 2015.
6 Dimopoulous, MA, San-Miguel, JF, Anderson, KC. Emerging therapies for the treatment of relapsed or refractory multiple myeloma. European Journal of Haematology. 2011; Jan 86(1):1-15.
7 Ferlay J, et al. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013. Available from: http://globocan.iarc.fr, accessed on 15/January/2015.
8 National Cancer Institute. SEER Stat Fact Sheets: Myeloma. http://seer.cancer.gov/statfacts/html/mulmy.html.
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