Amgen and UCB’s bone-forming antibody drug candidate Evenity™ (romosozumab) met primary and secondary endpoints in the Phase III ARCH study in postmenopausal women with osteoporosis at high risk of fracture. However, women treated using the sclerostin-targeting monoclonal antibody (mAb) were also at a higher risk of serious cardiovascular adverse events than those receiving the active comparator alendronate.

Evenity is already undergoing regulatory review in the U.S., Japan, and Canada, based on the 7180-patient Phase III FRAME study, and Amgen and UCB say the ARCH data will now also be brought into the FDA’s review of the antibody. Approval isn’t expected in the U.S. this year. Preparation for regulatory submission in the EU is continuing as planned, however, the firms stated.

The 4093-patient ARCH study evaluated Evenity in postmenopausal women with osteoporosis who were at high risk of fracture. The trial compared therapy with Evenity for 12 months followed by alendronate treatment, with alendronate therapy alone. Topline data from the study showed that the Evenity-based regimen reduced the risk of new vertebral fractures through 24 months by 50%, compared with alendronate therapy. Evenity-treated women also exhibited a 27% reduction in the relative risk of clinical fracture (nonvertebral fracture and clinical vertebral fracture) and a 19% reduction in the risk of nonvertebral fractures, including a nominally significant reduction in hip fractures.

The incidence of cardiovascular serious adverse events at 12 months was 2.5% for the Evenity-treated women, compared with 1.9% for women treated using alendronate alone.

“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., evp of R&D 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.”

“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,” added Iris Loew-Friedrich, Ph.D., UCB’s CMO.

Evenity is designed to work by boosting bone formation and decreasing bone resorption. The antibody is already under regulatory review in the U.S., Canada, and Japan, based on data from the 7180-patient FRAME study in postmenopausal women with osteoporosis. FRAME compared Evenity with placebo in reducing the risk of new vertebral fractures through to 12 months, and then compared Evenity treatment for 12 months followed by denosumab therapy for 12 months, compared with placebo then denosumab therapy. 

Evenity has been developed by Amgen and UCB as part of their long-term collaboration and license agreement, signed in 2004, to develop antibody products targeting sclerostin.

Belgium-based UCB reported revenues of €1.12 billion (approximately $1.26 billion) in the first 3 months of 2017, up 15% on the equivalent 2016 period. The firm’s biggest selling product, Cimzia® (certolizumab pegol), is approved in specified markets for treating ankylosing spondylitis, axial spondyloarthritis, Crohn’s disease, psoriatuc arthritis, and rheumatoid arthritis. Global sales of Cimzia were €317 million (approximately $356 million)  in the first quarter of 2017, up 13%. At the start of 2017 UCB and partner Dermira reported positive topline data from a Phase III study evaluating Cimzia in adults with moderate-to-severe chronic plaque psoriasis. Regulatory submissions are projected for Q3 2017. In February, the firm initiated a new Phase III study with Cimzia in adults with psoriasis and psoriatic arthritis to support line extension in Japan.

UCB received a Complete Response Letter (CRL) from the FDA in March relating to its submission of Cimzia for treating polyarticular juvenile idiopathic arthritis. The CRL cited concerns about the reliability of submitted pharmacokinetic data.

Within the last few days, Amgen separately reported submitting a Biologics License Application (BLA) to the FDA for its human calcitonin gene-related peptide (CGRP)-targeting mAb erenumab as a treatment for preventing migraine. If approved, the drug will be co-commercialized in the U.S. by Amgen and Novartis, as part of an April 2017 extension to the firms’ partnership for migraine and Alzheimer’s disease therapies, originally signed in 2015.