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【Press Release】CONSISTENT RESULTS OF JAPANESE POSTMENOPAUSAL WOMEN WITH OSTEOPOROSIS IN THE PHASE 3 STUDY OF ROMOSOZUMAB PRESENTED AT THE ANNUAL MEETING OF JAPAN OSTEOPOROSIS SOCIETY

October 20, 2017

Japanese Sub-group Analysis Demonstrated
the Consistent Outcomes of Efficacy and Safety in FRAME Study

TOKYO (Oct. 20, 2017) – Amgen Astellas BioPharma K.K. (Headquarters, Tokyo; General Manager and Representative Director: Steve Sugino, “Amgen Astellas”) today announced sub-group analysis results of Japanese postmenopausal women with osteoporosis from the Phase 3 placebo-controlled FRActure study in postmenopausal woMen with ostEoporosis (FRAME) at the annual meeting of Japan Osteoporosis Society in Osaka.

Of overall 7,180 enrolled subjects in FRAME, 492 (6.9%) were Japanese. The Japanese sub-group analysis was not powered for fracture endpoints. However, a reduction in new vertebral and clinical fractures was demonstrated at 12 and 24 months that was consistent with that observed in the overall study population. The results of the Japanese sub　group in this phase III trial was announced as the first time to demonstrate the fracture risk reduction as early as one year. Romosozumab acts to inhibit of protein sclerostin, and has a dual effect on bone, both increasing bone formation and decreasing bone resorption. The overall FRAME study previously demonstrated that Romosozumab reduced new vertebral fracture significantly through months 12 and 24 and reduced the incidence of clinical fractures (composite of vertebral and non-vertebral fractures) in postmenopausal women with osteoporosis through 12 months. The presented outcomes of the Japanese sub-group are consistent with the results in the overall study.

Results from the overall FRAME study showed that women receiving subcutaneous injection of romosozumab monthly experienced a statistically significant 73% reduction in the relative risk of new vertebral fracture through 12 months compared to placebo, and 75% reduction through 24 months in romosozumab followed by denosumab compared to placebo followed by denosumab, respectively. Japanese sub group also shows 55% and 63% reduction, respectively (p=0.15, 0.07, respectively). Additionally, patients receiving romosozumab experienced a statistically significant 36% reduction in the relative risk of a clinical fracture through 12 months compared to those receiving placebo, and 50% reduction (p=0.19) in Japanese sub-group. Also, an increase of P1NP and a decrease of CTX reflecting of the effect of romosozumab in bone turnover, and, significant increase of BMD at lumbar spine, total hip or femoral neck are shown in Japanese sub group as similar in overall FRAME study.

The percentage of Japanese 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 as similar to overall FRAME study. In the overall FRAME study, there were two positively adjudicated events of osteonecrosis of the jaw (ONJ) in the romosozumab treatment group, one after completing romosozumab dosing and the other patient, who happened to be from Japan 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 in the overall study..

“Treatment data show that only 18.7% of women who have experienced hip fracture are given antiosteoporosis therapy2, despite the fact that patients who experience an osteoporotic fracture are twice as likely to suffer a future fracture1,” said study lead author Akimitsu Miyauchi, M.D., FACP, predident of Miyauchi Medical Center. “The consistent outcomes in Japanese sub-group from FRAME results demonstrate that romosozumab has the potential to reduce the risk of new vertebral and clinical fractures within 12 months, in addition to showing significant improvements in bone mass, with sustained benefits upon transition to denosumab, thereby addressing a critical treatment need for patients at increased risk of fracture.”

“Romosozumab with its dual effect of stimulating bone formation and antiresorptive action has the potential to play a distinct and important role in the treatment of women with postmenopausal osteoporosis at high risk of fracture,” said Kurt Rimkus, M.D., executive director of Research and Development at Amgen Astellas. “We are proud to be convinced to provide this potential treatment option available to patients by demonstrating these consistent results in Japanese sub group with overall FRAME study.”

FRAME is a Phase 3 multi-center, international, randomized, double-blind, placebo-controlled, parallel-group study to assess the efficacy and safety of romosozumab treatment in postmenopausal women with osteoporosis. The study evaluated 12 months of romosozumab treatment versus placebo followed by 12 months of open-label denosumab treatment for both arms. The purpose of this study was to determine if treatment with romosozumab is effective in reducing the risk of fracture in women with postmenopausal osteoporosis through months 12 and 24.

Further analysis for Japanese sub group of the Phase 3 FRAME extension study data is ongoing and will be submitted to a future medical conference and for publication.

About Romosozumab
Romosozumab is an investigational bone-forming monoclonal antibody and is not approved by any regulatory authority for the treatment of osteoporosis. It is designed to work by inhibiting 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. In Japan, Amgen Astellas and Astellas are co-developing romosozumab.

About the FRAME study
FRAME is a multi-center, 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 of symptomatic vertebral and non-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.

About Amgen Astellas BioPharma K.K.
Amgen Astellas BioPharma K.K. is a Japanese company that began operations on October 1, 2013, to provide breakthrough-science-based medicines to help address unmet medical needs of patients in Japan. The company is a joint venture between Amgen, one of the world’s leading independent biotechnology companies, and Astellas Pharma Inc., a leading Tokyo-based R&D oriented global pharmaceutical company. The joint venture will become a wholly-owned Amgen affiliate as soon as 2020. Amgen Astellas leverages the capabilities of both companies – Amgen’s science and pipeline candidates coupled with Astellas’ deep knowledge of Japanese patient and physician needs, long-term commercial and regulatory experience, and strong presence as a leading company in Japan – to contribute to the creation of a healthy society.

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 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.

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References

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.
Hagino H et al. The Risk of a Second Hip Fracture in Patients after Their First Hip Fracture. Calcif Tissue Int (2012) 90:14–21.