Amgen and UCB, have announced that the Evenity (romosozumab) ARCH study met both primary endpoints and the key secondary endpoint. At the primary analysis, treatment with Evenity for 12 months followed by alendronate significantly reduced the incidence of new vertebral fractures through 24 months, clinical fractures (primary endpoints) and non-vertebral fractures (key secondary endpoint) in postmenopausal women with osteoporosis at high risk for fracture, compared to alendronate alone. An imbalance in positively adjudicated cardiovascular serious adverse events was observed as a new safety signal (2.5 per cent Evenity versus 1.9 per cent alendronate at 12 months).

"The efficacy results from this study comparing Evenity to an active control are robust. At the same time, the newly observed cardiovascular safety signal will have to be assessed as part of the overall benefit: risk profile for Evenity," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "Together with UCB, we will engage with global regulators and medical experts in the field to conduct a thorough evaluation of these data."

Evenity is an investigational bone-forming agent that rapidly increases bone formation and reduces bone resorption simultaneously, increases bone mineral density and reduces the risk of fracture. In this study, women received subcutaneous injection of Evenity monthly for 12 months followed by oral alendronate weekly for at least 12 months. At 24 months, women in the Evenity treatment group experienced a statistically significant 50 percent reduction in the relative risk of a new vertebral (spine) fracture compared to those receiving alendronate alone. Women in the Evenity treatment group also experienced a statistically significant 27 per cent reduction in the relative risk of clinical fracture (non-vertebral fracture and clinical vertebral fracture) at the primary analysis. Additionally, non-vertebral fractures were statistically significantly reduced by 19 per cent in the Evenity treatment group, including a nominally significant reduction in hip fractures.

"We are impressed with the statistically significant superior fracture risk reduction of Evenity over alendronate, a current standard of care in osteoporosis. When we think that patients who have had a fracture are highly likely to suffer another one, the importance of post-fracture care cannot be emphasized enough," said Iris Loew-Friedrich, UCB's chief medical officer. "We are working on understanding the observed cardiovascular safety signal and will continue to discuss these results with global regulators and experts in the field."

Overall adverse events and serious adverse events were generally similar between the treatment groups throughout the study and also in the initial 12-month Evenity treatment period. In the initial 12-month Evenity treatment period, the three most commonly reported adverse events in both arms were nasopharyngitis, back pain and arthralgia. Injection site reactions were reported in 4.4 percent of patients in the Evenity treatment group and 2.6 per cent in the alendronate group during the initial 12-month period.

Most injection site reactions were reported as mild in severity. During the open-label alendronate period, there were two positively adjudicated events of osteonecrosis of the jaw, one in a patient treated with Evenity followed by alendronate and one treated with alendronate alone. There were six patients with positively adjudicated events of atypical femoral fracture during the open-label alendronate period (two patients treated with Evenity followed by alendronate and four treated with alendronate alone). The patient incidence of positively adjudicated cardiovascular serious adverse events at 12 months was 2.5 per cent in the Evenity group compared to 1.9 per cent in the alendronate group. No imbalance in cardiovascular serious adverse events was seen in the 7,180-patient placebo-controlled FRAME study.

Regulatory submissions for Evenity based on the FRAME study results are currently under review with the US Food and Drug Administration (FDA), Health Canada and the Pharmaceuticals and Medical Devices Agency (PMDA) in Japan. Amgen has agreed with the FDA that the ARCH data should be considered in the regulatory review prior to the initial marketing authorization, and as a result the company does not expect approval of Evenity in the U.S. to occur in 2017.  Engagement with PMDA and Health Canada will occur as part of the ongoing review process. The preparation for the European regulatory submission will continue as planned. Further analysis of the phase 3 ARCH study data is ongoing and will be submitted to a future medical conference and for publication.