THOUSAND OAKS, Calif. and
SOUTH SAN FRANCISCO, Calif.,
Dec. 6, 2014 /PRNewswire/
-- Amgen (NASDAQ: AMGN) and its subsidiary Onyx
Pharmaceuticals, Inc., announced today results of the Phase 3
ASPIRE (CArfilzomib, Lenalidomide, and DexamethaSone
versus Lenalidomide and Dexamethasone for the treatment of
PatIents with Relapsed Multiple
MyEloma) trial, which evaluated Kyprolis®
(carfilzomib) for Injection plus Revlimid®
(lenalidomide) and dexamethasone (KRd) compared with
Revlimid and dexamethasone (Rd) in patients with relapsed
multiple myeloma. As previously reported, the ASPIRE study
met its primary endpoint by demonstrating that KRd significantly
extended the time patients lived without their disease worsening,
or progression-free survival (PFS), by 26.3 months compared to 17.6
months with Rd (HR=0.69; 95 percent CI: 0.57-0.83;
p<0.0001), an 8.7 month improvement in PFS.
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The results from ASPIRE (abstract 79) will be featured during
the 56th American Society of Hematology (ASH) Annual
Meeting and Exposition press briefing on Saturday, December 6 at 8
a.m. PT and were published in the New England Journal of
Medicine. Keith Stewart, M.B.,
Ch.B., dean for research at Mayo Clinic in Arizona and principal investigator will
present these results in an oral session at ASH on Sunday, December 7 at 12
p.m. PT.
Secondary endpoints, which are being presented for the first
time, included overall survival (OS), overall response rate (ORR),
duration of response (DOR), health-related quality of life (HR-QoL)
measures and safety. While the data for median OS are not yet
mature based on the prespecified statistical boundary at the
interim (p=0.005), the analysis showed a trend in favor of
KRd compared with Rd (HR=0.79; 95 percent CI: 0.63-0.99; one-sided
p=0.018, two-sided p=0.04). Patients will continue to
be monitored for OS. The ORR was 87.1 percent with KRd and 66.7
percent with Rd (one-sided p<0.0001, two-sided
p<0.001). In the KRd and Rd groups, 14 percent versus 4.3
percent of patients achieved a stringent complete response, a
measurement indicating superior depth of response. Median DOR was
28.6 months (KRd) and 21.2 months (Rd). KRd consistently improved
Global HR-QoL compared with Rd over 18 cycles of treatment
(one-sided p=0.0001, two-sided p<0.001).
"Nearly all patients with multiple myeloma experience a relapse
following treatment, underscoring the need for new options that not
only extend the time patients live without their disease
progressing, but also improve the depth and duration of a response
to treatment," said Dr. Stewart. "The combination of carfilzomib,
lenalidomide and low-dose dexamethasone generates deep and durable
responses, provides a clinically meaningful improvement in
progression-free survival and promises to be an important
advancement in the treatment of myeloma."
Treatment discontinuation due to an adverse event (AE) occurred
in 15.3 percent (KRd) versus 17.7 percent (Rd) of patients. In the
KRd arm, 7.7 percent versus 8.5 percent (Rd) of patients died while
still on study treatment or within 30 days of receiving the last
dose of study treatment. The most common hematologic
treatment-emergent AEs (≥grade 3) included neutropenia (29.6
percent [KRd] versus 26.5 percent [Rd]), anemia (17.9 percent [KRd]
versus 17.2 percent [Rd]) and thrombocytopenia (16.6 percent [KRd]
versus 12.3 percent [Rd]). The most common nonhematologic
treatment-emergent AEs (≥grade 3) included hypokalemia (9.4 percent
[KRd] versus 4.9 percent [Rd]), fatigue (7.7 percent [KRd] versus
6.4 percent [Rd]) and diarrhea (3.8 percent [KRd] versus 4.1
percent [Rd]). Other treatment-emergent AEs of interest (all
grade) included dyspnea (19.4 percent [KRd] versus 14.9 percent
[Rd]), hypertension (14.3 percent [KRd] versus 6.9 percent [Rd]),
acute renal failure (grouped term: 8.4 percent [KRd] versus 7.2
percent [Rd]), cardiac failure (grouped term: 6.4 percent [KRd]
versus 4.1 percent [Rd]) and ischemic heart disease (5.9 percent
[KRd] versus 4.6 percent [Rd]). Lastly, rates of peripheral
neuropathy (grouped term) were 17.1 percent (KRd) and 17.0 percent
(Rd), respectively.
"Delivering new potential treatment options exemplifies Onyx and
Amgen's commitment to advancing the care of patients with multiple
myeloma," said Pablo J. Cagnoni,
M.D., president, Onyx Pharmaceuticals, Inc. "The results from the
Phase 3 ASPIRE study bring us one step closer to establishing
Kyprolis as a backbone of therapy in the treatment of multiple
myeloma."
Results from the ASPIRE trial will form the basis for regulatory
submissions throughout the world beginning in the first half of
2015. In the U.S., the data may support the conversion of
accelerated approval to full approval and expand the current
indication.
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 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 PFS, defined as the time from
treatment initiation to disease progression or death. Secondary
endpoints included OS, ORR, DOR, disease control rate, duration of
disease control, change over time in HR-QoL and safety. Patients
were randomized to receive Kyprolis (20 mg/m2 on days 1
and 2 of cycle 1 only, then 27 mg/m2 subsequently),
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. In the Kyprolis arm, patients were given a 10
minute infusion on days 1, 2, 8, 9, 15 and 16. Kyprolis was omitted
on days 8 and 9 during cycles 13-18 and not administered beyond 18
cycles. The study randomized 792 patients at sites in North America, Europe and Israel.
Onyx conducted the ASPIRE trial under a Special Protocol
Assessment (SPA) from the U.S. Food and Drug Administration (FDA)
and has received Scientific Advice from the European Medicines
Agency (EMA) on the design and planned analysis of the study.
Amgen Webcast Investor Meeting
Amgen will host a
webcast investor meeting on Monday, December
8, at 12 p.m. PT. Sean E. Harper, M.D., executive vice president
of Research and Development at Amgen, and Pablo J. Cagnoni, M.D., president of Onyx
Pharmaceuticals Inc., along with members of Amgen's clinical
development team and clinical investigators, will participate in
the investor meeting to discuss data presented at ASH, including
the results of the pivotal Kyprolis ASPIRE study and
BLINCYTOTM (blinatumomab) studies in acute lymphoblastic
leukemia and diffuse large B-cell lymphoma.
Live audio of the investor meeting will be simultaneously
broadcast over the Internet and will be available to members of the
news media, investors and the general public.
The webcast, as with other selected presentations regarding
developments in Amgen's business given by management at certain
investor and medical conferences, can be found on Amgen's website,
www.amgen.com, under Investors. Information regarding presentation
times, webcast availability and webcast links are noted on Amgen's
Investor Relations Events Calendar. The webcast will be archived
and available for replay for at least 90 days after the event.
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. In the U.S.,
approximately 70,000 people are living with multiple myeloma and
approximately 24,000 new cases are diagnosed annually.1
Worldwide, nearly 230,000 people are living with multiple myeloma
and approximately 114,000 new cases are diagnosed
annually.2 In Europe,
approximately 89,000 people are living with multiple myeloma and
approximately 39,000 new cases are diagnosed
annually.3
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 marketed in the U.S. by Onyx Pharmaceuticals, Inc.,
an Amgen subsidiary.
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
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 (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.
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 biologics manufacturing 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 the world's
largest independent biotechnology company, 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.
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.
REVLIMID® is a registered trademark of Celgene
Corporation.
Forward-Looking Statements
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contains forward-looking statements that are based on the current
expectations and beliefs of Amgen Inc. and its subsidiaries (Amgen)
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CONTACT: Amgen, Thousand
Oaks
Kristen Davis, 805-447-3008 (Amgen
media)
Lindsay Treadway, 650-266-5346 (Onyx
media)
Arvind Sood, 805-447-1060
(investors)
References
- National Cancer Institute. SEER Stat Fact Sheets: Myeloma.
Available at http://seer.cancer.gov/statfacts/html/mulmy.html.
- International Agency for Research on Cancer, GLOBOCAN 2012
database. Available at http://globocan.iarc.fr/.
- Cancer Research UK. "Myeloma Incidence Statistics." Available
at:
http://www.cancerresearchuk.org/cancer-info/cancerstats/types/myeloma/incidence/uk-multiple-myeloma-incidence-statistics#europeandworldwide.
To view the multimedia assets associated with this release,
please click:
http://www.multivu.com/players/English/7061859-amgen-onyx-american-society-of-hematology-annual-meeting-kyprolis-aspire/
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SOURCE Amgen