Amgen & UCB ‘s Romosozumab: Development Pathway and approval status

Amgen and UCB, a global biopharmaceutical company, announced the resubmission of the Biologics License Application (BLA) to the US Food and Drug Administration (FDA) for Evenity (romosozumab), an investigational monoclonal antibody for the treatment of osteoporosis in postmenopausal women at high risk for fracture. Evenity increases bone formation and reduces bone resorption simultaneously to increase bone mineral density (BMD) and reduce the risk of fracture.

Resubmisison of BLA: What’s add on

The BLA for Evenity now adds results from two more recent pivotal phase 3 trials: the ARCH study, an alendronate-active comparator trial including 4,093 postmenopausal women with osteoporosis who experienced a fracture, and the BRIDGE study, including 245 men with osteoporosis.

Once BLA submitted what next?
The FDA will evaluate the clinical benefit: risk profile of Evenity, including the cardiovascular safety signal seen in the ARCH study, for the potential to reduce the risk of fractures and increase BMD in postmenopausal women with osteoporosis. The original FDA submission included data from a comprehensive phase 1 and phase 2 programme and the phase 3 placebo-controlled FRAME study, including 7,180 postmenopausal women with osteoporosis.

Approval in other region

The European Medicines Agency (EMA) and the Pharmaceuticals and Medical Device Agency (PMDA) in Japan are currently reviewing marketing applications for Evenity and interactions with the agencies are ongoing.

How it acts?
Evenity 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 activity of sclerostin, which enables Evenity to rapidly increase bone formation and reduce bone resorption simultaneously. Evenity has been studied for its potential to reduce the risk of fractures in an extensive global phase 3 program. This program included two large fracture trials comparing Evenity to either placebo or active comparator in more than 11,000 postmenopausal women with osteoporosis. Amgen and UCB are co-developing Evenity.

Clinical Trials for Evenity
FRAME (FRActure study in postmenopausal woMen with ostEoporosis) is a randomized, double-blind, placebo-controlled study that evaluated 7,180 postmenopausal women with osteoporosis. The study evaluated the effectiveness of Evenity treatment (210 mg), compared with placebo, in reducing the risk of new vertebral fractures through 12 months. The study also evaluated the effectiveness of treating with Evenity for 12 months followed by denosumab for 12 months, compared with placebo followed by denosumab, in reducing the risk of new vertebral fractures through 24 months.

ARCH (Active-contRolled fraCture study in postmenopausal women with osteoporosis at High risk of fracture) is a randomized, double-blind, alendronate-controlled study of Evenity in 4,093 postmenopausal women with osteoporosis at high risk for fracture based on previous fracture history. The study evaluated 12 months of Evenity treatment (210 mg) followed by at least 12 months of alendronate treatment (70 mg), compared with alendronate treatment alone, to determine effectiveness in reducing the incidence of clinical fracture (non-vertebral fracture and clinical vertebral fracture) and new vertebral fracture.

BRIDGE (placeBo-contRolled study evaluatIng the efficacy anD safety of romosozumab in treatinG mEn with osteoporosis) is a randomized, double-blind, placebo-controlled study of 245 men aged 55-90 years with osteoporosis and a history of fragility fracture (excluding hip fracture) or vertebral fracture. The study evaluated the effectiveness of Evenity treatment for 12 months, compared with placebo, in increasing BMD at the lumbar spine and the effect on BMD at the femoral neck and total hip.

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 translate a genetic discovery into a new medicine, turning conceptual science into a reality.