Denosumab Administered Twice-Yearly Reduced the Incidence of New Vertebral
Fractures by 62 Percent in Men with Non-Metastatic Prostate Cancer Undergoing
Androgen Deprivation Therapy
THOUSAND OAKS, Calif.,
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"The discovery of the RANK Ligand pathway represents a significant advance
in the understanding of bone biology," said
FREEDOM Osteoporosis Study Results: Significant Fracture Reduction Seen Across the Skeleton in Postmenopausal Women with Osteoporosis
Results from the FREEDOM (Fracture REduction Evaluation of Denosumab in Osteoporosis every six Months) study, showed that women receiving a subcutaneous shot of denosumab twice-yearly experienced a 68 percent reduction in the risk of suffering a vertebral (spine) fracture compared to those receiving placebo as well as a 40 percent reduction in the risk of suffering a hip fracture and a 20 percent reduction in the risk of suffering a nonvertebral fracture. Over the three years of this multi-center, randomized, double-blind, placebo-controlled study, women treated with denosumab experienced significant increases in BMD (8.8 percent at the lumbar spine and 6.4 percent at the total hip).(1)
"These results suggest that denosumab offers a new approach to prevention
of fractures in women with postmenopausal osteoporosis," said
Fracture is one of the most common health events suffered by postmenopausal women with osteoporosis.(3) Globally, one woman in three over 50 years of age will experience a fracture in her lifetime.(3) A woman who has broken a bone as a result of osteoporosis has more than an eight- out-of-ten chance of breaking another bone.(4) Half of women who break a hip, a life changing event, will permanently need assistance to walk.(5)
The overall incidence and type of side effects with denosumab were similar to placebo in the FREEDOM study. Rates of adverse events (AEs) were similar in both groups (93 percent). Rates of serious AEs were 25.8 percent for denosumab and 25.1 percent for placebo. The most common AEs across both treatment arms were arthralgia, back pain, hypertension and nasopharyngitis. There were no reported cases of osteonecrosis of the jaw among patients taking denosumab. Serious adverse events of skin infections, predominantly cellulitis, were reported more commonly in the denosumab group (0.4 percent vs. <0.1 percent). Mild, transient decreases in serum calcium were observed that had no apparent clinical significance.(1)
HALT Study Results: First Published Study to Demonstrate Fracture Prevention in Men with Non-Metastatic Prostate Cancer Undergoing ADT
Results from the HALT (Hormone AbLation Therapy) study in 1,468 men undergoing ADT for non-metastatic prostate cancer show that patients treated with denosumab experienced a 62 percent reduction in the risk of suffering a new vertebral fracture with denosumab compared to placebo at 36 months, with significant reduction observed as early as month-12.(2) Bone loss and increased fracture risk are serious and under-recognized consequences of ADT(6,7) and currently there are no approved therapies for these patients.
In this multi-center, randomized, double-blind, placebo-controlled study, men receiving 60 mg denosumab administered subcutaneously experienced a 6.7 percent increase in BMD at the lumbar spine compared to those receiving placebo (primary endpoint) at 24 months. Increases in BMD at the lumbar spine were observed as early as one month after starting treatment with denosumab and continued to increase throughout the study. In addition, denosumab produced significant increases in BMD at non-vertebral sites (total hip 4.8 percent, femoral neck 3.9 percent, and distal 1/3 radius 5.5 percent), compared to placebo.(2)
"Bone loss and fractures are an important but often unrecognized problem
for prostate cancer survivors. Bone loss is an early adverse effect and even
short-term androgen deprivation therapy negatively impacts skeletal health.
Prevention of bone loss and fractures has been a key unmet medical need for
men with prostate cancer," said
In the HALT trial, the overall incidence and type of side effects with denosumab were similar to placebo. Rates of AEs were similar in both groups (87 percent). Rates of serious AEs were 35 percent for denosumab and 31 percent for placebo. The most common AEs across both treatment arms were arthralgia, back pain, constipation, pain in extremity, and hypertension. There were no reported cases of osteonecrosis of the jaw among patients treated with denosumab. More patients receiving denosumab developed cataracts, though none were considered treatment-related. One patient in the denosumab arm developed hypocalcemia, versus none in the placebo arm. New primary malignancies were reported in 5 percent of patients in each group. Serious AEs of infections were reported in 6 percent of denosumab-treated patients and in 5 percent of placebo-treated patients.(2)
"
About Denosumab
Denosumab is the first fully human monoclonal antibody in late stage clinical development that specifically targets RANK Ligand, an essential regulator of osteoclasts (the cells that break down bone). Denosumab is being investigated for its potential to inhibit all stages of osteoclast activity through a targeted mechanism. Denosumab is being studied in a range of bone loss conditions including postmenopausal osteoporosis and bone loss in patients undergoing hormone ablation for prostate and breast cancer.
In
Osteoporosis: Impact and Prevalence
Often referred to as the "silent epidemic," osteoporosis is a global problem that is increasing in significance as the population of the world both increases and ages. The World Health Organization (WHO) has recently identified osteoporosis as a priority health issue along with other major non-communicable diseases.
The economic burden of osteoporosis is comparable to that of other major chronic diseases; for example, in the U.S., the costs associated with osteoporosis-related fractures are equivalent to those of cardiovascular disease and asthma.(8,9,10) It has been reported that osteoporosis results in more hospital bed-days than stroke, myocardial infarction or breast cancer.(11)
Bone Loss Due to Hormone Ablation Therapy
Worldwide, prostate cancer and breast cancer are two of the most frequent types of cancer affecting men and women, respectively.(12) In the U.S., prostate cancer is the most common cancer in men and breast cancer is the most common cancer in women. It is common for prostate cancer and breast cancer patients to receive hormone ablation therapies that can lead to a decrease in bone mass and increased risk of fractures. Currently there are no approved therapies for bone loss in patients undergoing hormone ablation for either prostate or breast cancer.
About
Forward-Looking Statements
This news release contains forward-looking statements that are based on
management's current expectations and beliefs and are subject to a number of
risks, uncertainties and assumptions that could cause actual results to differ
materially from those described. All statements, other than statements of
historical fact, are statements that could be deemed forward-looking
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other such estimates and results. Forward-looking statements involve
significant risks and uncertainties, including those discussed below and more
fully described in the
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. 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 after they are on the market. Our business may be impacted by government investigations, litigation and products liability claims. We depend on third parties for a significant portion of our manufacturing capacity for the supply of certain of our current and future products and limits on supply may constrain sales of certain of our current products and product candidate development.
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CONTACT:
Arvind Sood: (805) 447-1060 (investors)
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References
1. Cummings SR, et al. Twice Yearly Denosumab, a Monoclonal Antibody to
RANK-ligand, for Prevention of Fractures in Postmenopausal Women with
Osteoporosis. N Engl J Med, 2009 Aug. 20; published online at
www.nejm.org on
2. Smith MR, et al. Denosumab for the Prevention of Bone Loss and
Fractures in Men Receiving Androgen Deprivation Therapy in
Non-Metastatic Prostate Cancer. N Engl J Med, 2009 Aug. 20; published
online at www.nejm.org on
3. Melton LJ, et al. (1992) Perspective. How Many Women Have Osteoporosis?
J Bone Miner Res, 1992;7:1005
4. Kanis JA, et al. A Meta-Analysis of Previous Fracture and Subsequent
Fracture Risk. Bone, 2004;35:375.
5. Magaziner J, et al. Predictors of Functional Recovery One Year
Following Hospital Discharge for Hip Fracture: A Prospective Study. J
Gerontol, 1990;45:M101.
6. Higano 2008; Higano 2004; Conde 2003; Smith 2001; Pfeilschifter 2000.
7. Oefelein MG, Ricchiuti V, Conrad W, Resnick MI. Skeletal fractures
negatively correlate with overall survival in men with prostate cancer.
J Urol. 2002;168:1005-1007.
8. Burge R, et al. J Bone Miner Res. 2007; 22:465-475
9. "Osteoporosis Fast Facts."
10. "Economic Cost of Cardiovascular Diseases."
11. Lippuner K, et al. "Incidence and direct medical costs of
hospitalisations due to osteoporotic fractures in switzerland."
12. WHO. Media Center. Fact sheet No. 297.
SOURCE