THOUSAND OAKS, Calif. and
BRUSSELS, Sept. 18, 2016 /PRNewswire/ -- Amgen
(NASDAQ: AMGN) and UCB (Euronext Brussels: UCB) today announced
findings from the FRAME study showing that the investigational
agent romosozumab significantly reduced the incidence of new
vertebral fractures in postmenopausal women with osteoporosis
through 12 and 24 months, meeting the study's co-primary endpoints.
The results from the Phase 3 study, the first to evaluate fracture
risk reduction as early as one year as a primary endpoint, were
published in the New England Journal of Medicine (NEJM) and
presented today in an oral session at the Annual Meeting of the
American Society for Bone Mineral Research (ASBMR) in Atlanta. Romosozumab works by binding and
inhibiting the activity of the protein sclerostin, and as a result,
has a dual effect on bone, both increasing bone formation and
decreasing bone breakdown.
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"Treatment data show that only one in five women who have
experienced an osteoporotic fracture are started on treatment for
the disease1, despite the fact that patients who
experience an osteoporotic fracture are twice as likely to suffer a
future fracture2," said study lead author Felicia Cosman, M.D., medical director of the
Clinical Research Center at Helen Hayes Hospital and professor of
medicine at Columbia University College of
Physicians and Surgeons in New
York. "The FRAME results demonstrate that romosozumab, with
its dual effect of increasing bone formation and decreasing bone
resorption, has the potential to reduce the risk of new vertebral
and clinical fractures within 12 months, in addition to showing
improvements in bone mass, with sustained benefits upon transition
to denosumab, thereby addressing a critical treatment need for
patients at increased risk of fracture."
FRAME (FRActure study in postmenopausal woMen with
ostEoporosis), which enrolled 7,180 women, showed that those
randomly assigned to receive a monthly subcutaneous 210 mg dose of
romosozumab experienced a statistically significant 73 percent
reduction in the relative risk of a new vertebral (spine) fracture
through 12 months, the first co-primary endpoint, compared to those
receiving placebo (fracture incidence 0.5 percent versus 1.8
percent, respectively [p<0.001]). Of interest, the data
showed that by six months, new vertebral fractures occurred in 14
romosozumab and 26 placebo patients, and between six to 12 months,
fractures occurred in two additional romosozumab patients versus 33
additional placebo patients.
For those patients who received romosozumab in year one,
fracture risk reduction persisted through month 24 after both
groups transitioned to denosumab treatment in the second year of
the study; there was a statistically significant 75 percent
reduction in the risk of vertebral fracture at month 24 (the other
co-primary endpoint) in patients who received romosozumab followed
by denosumab versus placebo followed by denosumab (fracture
incidence 0.6 percent versus 2.5 percent, respectively
[p<0.001]). In the second year of the study, new
vertebral fractures occurred in five patients who transitioned from
romosozumab to denosumab and 25 patients who transitioned from
placebo to denosumab.
When looking at clinical fractures, which encompass all
symptomatic fractures (both non-vertebral and painful vertebral
fractures), patients receiving romosozumab experienced a
statistically significant 36 percent reduction in the relative risk
of a clinical fracture, a secondary endpoint, through 12 months
compared to those receiving placebo (fracture incidence 1.6 percent
versus 2.5 percent, respectively [p=0.008]). A 33 percent
reduction in relative risk of clinical fracture was observed
through 24 months after patients transitioned from romosozumab to
denosumab compared to patients transitioning from placebo to
denosumab (nominal p=0.002, adjusted p=0.096).
Romosozumab resulted in a 25 percent reduction compared to
placebo in the relative risk of non-vertebral fractures through
month 12, another secondary endpoint, but the reduced risk was not
statistically significant (fracture incidence 1.6 percent versus
2.1 percent, respectively, [p=0.096]). For the non-vertebral
fracture endpoint, the overall fracture incidence in the study was
lower than expected (2.1 percent in the placebo group in year one
versus an expected rate of 3.5 percent).
In a sub-study of 126 subjects, romosozumab increased bone
mineral density with gains of 9.7 percent and 4.7
percent from baseline by six months at the lumbar spine and
total hip, respectively, and gains of 13.3 percent and 6.8
percent at 12 months (all comparisons versus placebo
p<0.001). Bone mineral density continued to increase in
the romosozumab group after transitioning to denosumab, reaching
17.6 percent and 8.8 percent increases from baseline at the
lumbar spine and total hip, respectively, at 24 months
(p<0.001 compared to placebo-to-denosumab group for all
comparisons).
"We are pleased to see nearly 15 years of sclerostin antibody
research reinforced with these Phase 3 data. Romosozumab, with its
dual effect as a bone builder and anti-resorptive, has the
potential to play a distinct and important role in the treatment of
women with postmenopausal osteoporosis at increased risk of
fracture," said Sean E. Harper,
M.D., executive vice president of Research and Development at
Amgen. "These positive FRAME study results are the basis of our
Biologics Licensing Application that we submitted to the FDA in
July, and we look forward to working with regulatory authorities to
help make this potential treatment option available to
patients."
"Osteoporotic fractures are common, resulting in far-reaching
consequences for individuals and their families, as well as for
society as a whole," said Dr. Pascale
Richetta, head of bone and executive vice president, UCB.
"To reduce the growing global burden of this prevalent chronic
disease, more decisive steps need to be taken now for identifying,
diagnosing and appropriately treating people with osteoporosis at
an increased risk of fracture."
The percentage of patients with adverse events and serious
adverse events in the 12-month double-blind period and 24-month
study period were balanced overall between the treatment groups.
Injection site reactions, mostly mild in severity, were reported in
5.2 percent of patients in the romosozumab treatment group and 2.9
percent in the placebo group during the 12-month period. There were
two positively adjudicated events of osteonecrosis of the jaw in
the romosozumab treatment group, one after completing romosozumab
dosing and the other after completing romosozumab treatment and
receiving the initial dose of denosumab. There was one positively
adjudicated event of atypical femoral fracture after three months
of romosozumab treatment. Adjudicated serious cardiovascular events
and cardiovascular deaths were balanced between treatment
groups.
About Romosozumab
Romosozumab is an investigational bone-forming monoclonal agent and
is not approved by any regulatory authority for the treatment of
osteoporosis. It is designed to work by inhibiting the activity of
the protein sclerostin and has a dual effect on bone, both
increasing bone formation and decreasing bone breakdown.
Romosozumab is being studied for its potential to reduce the risk
of fractures in an extensive global Phase 3 program. This program
includes two large fracture trials comparing romosozumab to either
placebo or active comparator in more than 10,000 postmenopausal
women with osteoporosis. Amgen and UCB are co-developing
romosozumab.
About the FRAME study
FRAME is a multicenter, international, randomized, double-blind,
placebo-controlled, parallel-group study in postmenopausal women
with osteoporosis, defined as low bone mineral density at the total
hip or femoral neck. The study evaluated the effectiveness of
romosozumab treatment, compared with placebo, in reducing the risk
of new vertebral fractures through 12 months. The study also
further evaluated if romosozumab treatment for 12 months followed
by denosumab treatment for 12 months, compared with placebo
followed by denosumab treatment, was effective in reducing the risk
of new vertebral fractures through 24 months. In addition, clinical
fracture (a composite endpoint which encompasses all symptomatic
fractures, both non-vertebral and painful vertebral fractures) risk
reduction, non-vertebral fracture (fractures outside of the spine,
excluding sites that are not considered osteoporotic, fractures due
to high trauma or pathologic fractures) risk reduction and other
endpoints were assessed at 12 and 24 months.
7,180 patients were randomized 1:1 to receive either 210 mg
romosozumab subcutaneous (SC) monthly (QM) or placebo SC QM for the
12-month double-blind study period. After the placebo-controlled
study period, patients entered the open-label phase where all
patients received 60 mg denosumab SC every six months (Q6M) for 12
months, while remaining blinded to initial treatment. An additional
12 month extension period of open-label 60 mg denosumab SC Q6M is
currently ongoing.
About Prolia® (denosumab)
Prolia is indicated for the treatment of postmenopausal women with
osteoporosis at high risk for fracture, defined as a history of
osteoporotic fracture, or multiple risk factors for fracture; or
patients who have failed or are intolerant to other available
osteoporosis therapy. In postmenopausal women with osteoporosis,
Prolia reduces the incidence of vertebral, nonvertebral, and hip
fractures.
Prolia is indicated for treatment to increase bone mass in men
with osteoporosis at high risk for fracture, defined as a history
of osteoporotic fracture, or multiple risk factors for fracture; or
patients who have failed or are intolerant to other available
osteoporosis therapy.
Prolia is indicated as a treatment to increase bone mass in men
at high risk for fracture receiving androgen deprivation therapy
for nonmetastatic prostate cancer. In these patients Prolia also
reduced the incidence of vertebral fractures.
Prolia is indicated as a treatment to increase bone mass in
women at high risk for fracture receiving adjuvant aromatase
inhibitor therapy for breast cancer.
Important Safety Information (U.S.)
Contraindications
Prolia® is contraindicated in patients with
hypocalcemia. Pre‐existing hypocalcemia must be corrected prior to
initiating Prolia®. Prolia® is
contraindicated in women who are pregnant and may cause fetal harm.
Prolia® is contraindicated in patients with a history of
systemic hypersensitivity to any component of the product.
Reactions have included anaphylaxis, facial swelling and
urticaria.
Same Active Ingredient
Prolia® contains the same active ingredient (denosumab)
found in XGEVA®. Patients receiving Prolia®
should not receive XGEVA®.
Hypersensitivity
Clinically significant hypersensitivity including anaphylaxis has
been reported with Prolia®. Symptoms have included
hypotension, dyspnea, throat tightness, facial and upper airway
edema, pruritus, and urticaria. If an anaphylactic or other
clinically significant allergic reaction occurs, initiate
appropriate therapy and discontinue further use of
Prolia®.
Hypocalcemia
Hypocalcemia may worsen with the use of Prolia®,
especially in patients with severe renal impairment. In patients
predisposed to hypocalcemia and disturbances of mineral metabolism,
clinical monitoring of calcium and mineral levels is highly
recommended within 14 days of Prolia® injection.
Adequately supplement all patients with calcium and vitamin D.
Osteonecrosis of the Jaw (ONJ)
ONJ, which can occur spontaneously, is generally associated with
tooth extraction and/or local infection with delayed healing, and
has been reported in patients receiving Prolia®. An oral
exam should be performed by the prescriber prior to initiation of
Prolia®. A dental examination with appropriate
preventive dentistry is recommended prior to treatment in patients
with risk factors for ONJ such as invasive dental procedures,
diagnosis of cancer, concomitant therapies (e.g., chemotherapy,
corticosteroids, angiogenesis inhibitors), poor oral hygiene, and
co‐morbid disorders. Good oral hygiene practices should be
maintained during treatment with Prolia®. The risk of
ONJ may increase with duration of exposure to
Prolia®.
For patients requiring invasive dental procedures, clinical
judgment should guide the management plan of each patient. Patients
who are suspected of having or who develop ONJ should receive care
by a dentist or an oral surgeon. Extensive dental surgery to treat
ONJ may exacerbate the condition. Discontinuation of
Prolia® should be considered based on individual
benefit‐risk assessment.
Atypical Femoral Fractures
Atypical low‐energy, or low trauma fractures of the shaft have been
reported in patients receiving Prolia®. Causality has
not been established as these fractures also occur in osteoporotic
patients who have not been treated with anti‐resorptive agents.
During Prolia® treatment, patients should be advised
to report new or unusual thigh, hip, or groin pain. Any patient who
presents with thigh or groin pain should be evaluated to rule out
an incomplete femur fracture. Interruption of Prolia®
therapy should be considered, pending a risk/benefit assessment, on
an individual basis.
Serious Infections
In a clinical trial (N=7,808) in women with postmenopausal
osteoporosis, serious infections leading to hospitalization were
reported more frequently in the Prolia® group than in
the placebo group. Serious skin infections, as well as infections
of the abdomen, urinary tract and ear were more frequent in
patients treated with Prolia®.
Endocarditis was also reported more frequently in
Prolia®‐treated patients. The incidence of opportunistic
infections and the overall incidence of infections were similar
between the treatment groups. Advise patients to seek prompt
medical attention if they develop signs or symptoms of severe
infection, including cellulitis.
Patients on concomitant immunosuppressant agents or with
impaired immune systems may be at increased risk for serious
infections. In patients who develop serious infections while on
Prolia®, prescribers should assess the need for
continued Prolia® therapy.
Dermatologic Adverse Reactions
In the same clinical trial in women with postmenopausal
osteoporosis, epidermal and dermal adverse events such as
dermatitis, eczema and rashes occurred at a significantly higher
rate with Prolia® compared to placebo. Most of these
events were not specific to the injection site. Consider
discontinuing Prolia® if severe symptoms develop.
Musculoskeletal Pain
Severe and occasionally incapacitating bone, joint, and/or muscle
pain has been reported in patients taking Prolia®.
Consider discontinuing use if severe symptoms develop.
Suppression of Bone Turnover
In clinical trials in
women with postmenopausal osteoporosis, Prolia® resulted
in significant suppression of bone remodeling as evidenced by
markers of bone turnover and bone histomorphometry. The
significance of these findings and the effect of long‐term
treatment are unknown. Monitor patients for these consequences,
including ONJ, atypical fractures, and delayed fracture
healing.
Adverse Reactions
The most common adverse reactions (>5% and more common than
placebo) in women with postmenopausal osteoporosis are back pain,
pain in extremity, musculoskeletal pain, hypercholesterolemia, and
cystitis. The most common adverse reactions (> 5% and more
common than placebo) in men with osteoporosis are back pain,
arthralgia, and nasopharyngitis. Pancreatitis has been reported
with Prolia®.
In women with postmenopausal osteoporosis, the overall incidence
of new malignancies was 4.3% in the placebo group and 4.8% in the
Prolia® group. In men with osteoporosis, new
malignancies were reported in no patients in the placebo group and
4 (3.3%) patients in the Prolia® group. A causal
relationship to drug exposure has not been established.
The most common (per patient incidence ≥ 10%) adverse reactions
reported with Prolia® in patients with bone loss
receiving ADT for prostate cancer or adjuvant AI therapy for breast
cancer are arthralgia and back pain. Pain in extremity and
musculoskeletal pain have also been reported in clinical trials.
Additionally, in Prolia®‐treated men with nonmetastatic
prostate cancer receiving ADT, a greater incidence of cataracts was
observed.
Denosumab is a human monoclonal antibody. As with all
therapeutic proteins, there is potential for immunogenicity.
Prolia® Postmarketing Active Safety
Surveillance Program
The surveillance program is available to collect information from
prescribers on specific adverse events. Please see
www.proliasafety.com or call 1‐800‐772‐6436 for more
information.
For more information, please see the Prolia Important Safety
Information, Prescribing Information, and Medication Guide.
About the Amgen and UCB Collaboration
Since 2004,
Amgen and UCB have been working together under a collaboration and
license agreement to research, develop and market antibody products
targeting the protein sclerostin. As part of this agreement, the
two companies continue to collaborate on the development of
romosozumab for the treatment of osteoporosis. This gene-to-drug
project demonstrates how Amgen and UCB are joining forces to turn
genetic discoveries into new medicine, turning conceptual science
into a reality.
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.
About UCB
UCB, Brussels, Belgium
(www.ucb.com) is a global biopharmaceutical company focused on the
discovery and development of innovative medicines and solutions to
transform the lives of people living with severe diseases of the
immune system or of the central nervous system. With more than
7,700 people in approximately 40 countries, the company generated
revenue of € 3.9 billion in 2015. UCB is listed on Euronext
Brussels (symbol: UCB). Follow us on Twitter: @UCB_news
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CONTACT: Amgen, Thousand
Oaks
Kristen Davis, 805-447-3008
(media)
Kristen Neese, 805-313-8267
(media)
Arvind Sood, 805-447-1060
(investors)
CONTACT: UCB, Brussels
France Nivelle, Global
Communications, UCB
T +32.2.559.9178, france.nivelle@ucb.com
Laurent Schots, Media Relations,
UCB
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Antje Witte, Investor Relations,
UCB
T +32.2.559.94.14, antje.witte@ucb.com
Isabelle Ghellynck, Investor Relations, UCB
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1. Wilk A et al. Post-fracture pharmacotherapy for women with
osteoporotic fracture: analysis of a managed care population in the
USA. Osteoporosis Int.
2014;25(12):2777-2786.
2. International Osteoporosis Foundation. Stop at One. One Fracture
Leads to Another.
http://share.iofbonehealth.org/WOD/2012/patient_brochure/WOD12-patient_brochure.pdf.
Accessed August 29, 2016.
To view the original version on PR Newswire,
visit:http://www.prnewswire.com/news-releases/results-from-phase-3-frame-study-of-romosozumab-showed-significant-reductions-in-both-new-vertebral-and-clinical-fractures-in-postmenopausal-women-with-osteoporosis-300329792.html
SOURCE Amgen