Amgen Announces Positive Top-Line Results for Denosumab in Trial for Delay of Skeletal Related Events in Bone Metastases Patients Compared to Zometa(R)
Second of Three Pivotal Phase Three Bone Metastases Trials Meets Primary Endpoint Denosumab Delayed Time to Skeletal Related Events
THOUSAND OAKS, Calif., Aug. 3 /PRNewswire-FirstCall/ -- Amgen
(NASDAQ: AMGN) today announced positive top-line
results from a pivotal Phase 3 head-to-head trial evaluating
denosumab administered subcutaneously versus Zometa (zoledronic
acid) administered as an intravenous (IV) infusion in the treatment
of bone metastases in 1,776 advanced cancer patients with solid
tumors (not including breast and prostate cancer) or multiple
myeloma.
For the primary endpoint, patients treated with denosumab
experienced a similar time to first skeletal-related event (SRE)
(fracture, radiation to bone, surgery to bone, or spinal cord
compression) compared with those receiving Zometa (hazard ratio
0.84, 95 percent CI: 0.71-0.98), which is statistically significant
for non-inferiority (p<0.0007). Although numerically greater,
the delay in the time to first SRE associated with denosumab
treatment was not statistically superior compared to Zometa
(adjusted p=0.06) (secondary endpoint). The time to
first-and-subsequent SRE was also numerically greater but not
statistically superior compared to Zometa (hazard ratio 0.90, 95
percent CI: 0.77-1.04) (secondary endpoint).
Overall, the incidence of adverse events and serious adverse
events was consistent with what has previously been reported for
these two agents. Rates of osteonecrosis of the jaw (ONJ) were
balanced and infrequent in both treatment groups (10 patients
receiving denosumab as compared with 11 patients receiving Zometa).
Infectious adverse events were balanced between the two treatment
arms, as was overall survival and the time to cancer
progression.
"We are extremely pleased with these results, which continue to
demonstrate that inhibiting RANK Ligand with denosumab provides a
clinically meaningful benefit for advanced cancer patients with
solid tumors that have metastasized to the bone, and to patients
with multiple myeloma, both groups who routinely suffer SREs," said
Roger M. Perlmutter, M.D., Ph.D., executive vice president of
Research and Development at Amgen. "We are very encouraged by the
overall strength of the data, which we will present in a scientific
forum later this year. We are also looking forward to reviewing the
results of a final SRE study, in patients with advanced prostate
cancer, next year."
Bone metastases, the spread of tumors to the bone, are a serious
concern for many advanced cancer patients. When cancer spreads to
the bone, the growing cancer cells weaken and destroy the bone
around the tumor. This damage can result in a number of serious
bone complications, collectively called SREs.
Full safety and efficacy data will be submitted for presentation
at an upcoming medical meeting in the second half of this
year.
Study Design
This was an international Phase 3, randomized, doubleblind,
active controlled study comparing denosumab with Zometa in the
treatment of bone metastases in patients with advanced cancer
(excluding breast and prostate cancer) or multiple myeloma.
Patients enrolled in this event-driven study were randomized in a
one-to-one ratio to receive either 120 mg of denosumab
subcutaneously every four weeks (Q4W) or Zometa administered
intravenously at a dose of 4 mg single, 15 minute infusion every
four weeks.
In clinical trials thus far to test new medications for bone
metastases, treatment success has been measured by whether the bone
complications, or SREs, caused by the tumor are reduced or delayed.
The primary and secondary endpoints of the denosumab bone
metastases studies use a composite endpoint of four SREs -
fracture, radiation to bone, surgery to bone, and spinal cord
compression - to measure the effectiveness of denosumab versus
Zometa.
The primary endpoint was to evaluate if denosumab is
non-inferior to Zometa with respect to the first on-study SRE in
patients with advanced cancer (excluding breast and prostate
cancer) or multiple myeloma and bone metastases. Secondary
endpoints were to evaluate if denosumab is superior to Zometa with
respect to the first on-study SRE, as well as first-and-subsequent
on-study SREs, and to assess the safety and tolerability of
denosumab compared with Zometa.
About Denosumab and Amgen's Research in Bone Biology
Denosumab is the first fully human monoclonal antibody in late
stage clinical development that specifically targets RANK Ligand,
the essential regulator of osteoclasts (the cells that break down
bone). With more than 19,000 patients in trials across indications
worldwide, the denosumab development program is the largest ever
initiated by Amgen. This broad and deep development program
demonstrates Amgen's commitment to researching and delivering
pioneering medicines to patients with unmet medical needs. Amgen is
studying denosumab in numerous tumor types across the spectrum of
cancer induced bone disease. Over 11,000 patients have been
enrolled in the denosumab oncology clinical trials testing the drug
for bone loss and destruction associated with cancer
treatment-induced bone loss in breast and prostate cancers, for the
prevention of skeletal related events due to the spread of cancer
to the bone in multiple myeloma and multiple solid tumors, and for
its potential to delay bone metastases in prostate cancer.
Bone Metastases: Impact and Prevalence
Bone metastases, cancer cells that separate from tumors and
migrate to bone tissue where they settle and grow, occur in more
than 1.5 million people worldwide.(1) With improvements in cancer
care, including earlier diagnosis and new treatment options,
leading to increases in survival rates(2), the number of patients
developing metastatic disease secondary to a primary cancer is
increasing. Bone metastases are a significant problem for patients
with certain types of advanced cancer, with incidence rates of
nearly 100 percent in myeloma patients and as high as 75 percent in
solid tumor patients.
With bone metastases the growing cancer cells weaken and destroy
the bone around the tumor. The damage the tumor has caused to the
bone can result in a number of serious complications, collectively
called skeletal related events (SREs). These include fracture of a
bone, radiation to bone, surgery to bone, or spinal cord
compression. All are serious complications for advanced cancer
patients.
Regardless of the type of underlying cancer, the process by
which cancers invade and destroy bones is fundamentally the same.
At the center of this destructive process is a protein RANK Ligand
that is stimulated by the presence of cancer in the bone.
The economic burden of U.S. patients with bone metastases is
significant and was estimated to be $12.6 billion last year.(3)
Patients with bone metastases who experience an SRE incur
significantly higher medical costs compared with those who do not
experience an SRE.(4)
About Amgen
Amgen discovers, develops and delivers innovative human
therapeutics. A biotechnology pioneer since 1980, Amgen was one of
the first companies to realize the new science's promise by
bringing safe and effective medicines from lab, to manufacturing
plant, to patient. Amgen therapeutics have changed the practice of
medicine, helping millions of people around the world in the fight
against cancer, kidney disease, rheumatoid arthritis, and other
serious illnesses. With a deep and broad pipeline of potential new
medicines, Amgen remains committed to advancing science to
dramatically improve people's lives. To learn more about our
pioneering science and our vital medicines, visit
www.amgen.com.
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ZOMETA is a registered trademark of Novartis Oncology.
*Editors Note: The FDA has provisionally approved the trade name
Prolia(TM) for the proposed indications of treatment and prevention
of osteoporosis in postmenopausal women, and treatment and
prevention of bone loss in patients undergoing hormone ablation for
prostate or breast cancer. The Prolia(TM) trade name is only for
these indications and may not apply for other indications of
denosumab.
(1) Capanna R, Coia LR, Coleman R. et al. eds. Textbook of Bone
Metastases. Hoboken, NJ: Edition: John Wiley and Sons;
2005:105.
(2) Mundy GR. Metastasis to bone: causes, consequences and
therapeutic opportunities. Nat Rev Cancer. 2002
Aug;2(8):584-93.
(3) Schulman K and Kohles J. Cancer. 2007;109:2334-2342 (4) GVD/Barber ISPOR 2008 Poster; Schulman 2007; Delea et al. 2006 Amgen, Thousand Oaks Lisa Rooney, 805-447-6437 (media) Arvind Sood, 805-447-1060 (investors) (Logo: http://www.newscom.com/cgi-bin/prnh/20081015/AMGENLOGO)
Photo: http://www.newscom.com/cgi-bin/prnh/20081015/AMGENLOGO
http://photoarchive.ap.org/
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Source: Amgen
CONTACT: media, Lisa Rooney, +1-805-447-6437, or investors,
Arvind Sood,
+1-805-447-1060, both of Amgen, Thousand Oaks
Web Site: http://www.amgen.com
Posted: August 2009
