Amgen (NASDAQ: AMGN) and UCB (Euronext Brussels:UCB) today announced results from a Phase 2 trial evaluating romosozumab (AMG 785/CDP7851) in postmenopausal women with low bone mineral density (BMD). Published in the New England Journal of Medicine (NEJM), the trial demonstrated that, compared with placebo, romosozumab treatment for 12 months significantly increased BMD at the lumbar spine, total hip and femoral neck. Significant increases were also observed in the first BMD assessment at three months. Moreover, in exploratory analyses, increases observed at the lumbar spine and hip were significantly greater than those observed with current treatments FOSAMAX® (alendronate sodium) and FORTEO™/FORSTEO® (teriparatide).
"The results of the study demonstrate significantly increased BMD and stimulation of bone formation with romosozumab treatment in women with postmenopausal osteoporosis," said Michael McClung, M.D., director of the Oregon Osteoporosis Center and lead study investigator. "Additionally, romosozumab treatment resulted in greater increases in bone mineral density than those seen with both placebo and the active comparators. These data provide important insight into this medicine being developed for women with postmenopausal osteoporosis at high risk for fractures."
Romosozumab is an investigational medicine in Phase 3 clinical development for the treatment of osteoporosis in postmenopausal women and is not currently approved by any regulatory authority.
In this Phase 2 trial, each of the five romosozumab dose regimens significantly increased BMD compared with pooled placebo groups at the lumbar spine, total hip and femoral neck regions (all p<0.001). The largest increases were observed with the romosozumab 210 mg once-monthly dose, with mean increases compared with baseline of 11.3 percent at the lumbar spine, 4.1 percent at the total hip and 3.7 percent at the femoral neck.
Additionally, in exploratory analyses, BMD gains were significantly greater than active comparators at month 12, with romosozumab treatment achieving a mean increase of 11.3 percent at the lumbar spine compared to increases of 4.1 percent and 7.1 percent at the same region achieved with FOSAMAX and FORTEO, respectively. At the total hip, romosozumab treatment increased BMD 4.1 percent, while observed gains with FOSAMAX were 1.9 percent and with FORTEO were 1.3 percent (all p<0.001).
The comparators to romosozumab were placebo, oral FOSAMAX (70 mg weekly) and subcutaneous FORTEO (20 μg daily), both of which were open-label.
Adverse events were similar across groups, except for mild, generally non-recurring injection site reactions observed more frequently with romosozumab compared to placebo, but with no observed dose-related relationship. Most common adverse events included mild upper respiratory tract infection, pain in the back and joints, and headache. These reactions did not lead to study drug discontinuation or study withdrawal; the safety of romosozumab will be further addressed in subsequent larger studies.
"There remains a significant need for additional treatment options that form new bone. Romosozumab is designed to stimulate bone formation, which makes it different from most available treatments that reduce bone resorption," said Prof. Dr. Iris Loew-Friedrich, chief medical officer, UCB. "We are encouraged by the emerging efficacy and safety profile, and look forward to further investigating its potential in the ongoing global Phase 3 clinical program."
"Broken bones due to osteoporosis are common and can have a significant impact on the patient, her family and the healthcare system, yet the seriousness of this health event remains underappreciated, with only two-in-10 women receiving follow-up testing or treatment after they have broken a bone," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "With its bone-forming ability, romosozumab may result in new treatment strategies to help manage this disease."
The study was a Phase 2, multicenter, international, randomized, placebo-controlled, parallel-group, eight-arm study of 419 postmenopausal women aged 55 to 85 years with BMD T-score <–2.0 at the lumbar spine, total hip or femoral neck and >–3.5 at all three sites. Study participants were randomly assigned to receive subcutaneous romosozumab monthly (70, 140, or 210 mg) or every three months (140 or 210 mg), subcutaneous placebo, or oral FOSAMAX (70 mg weekly) or subcutaneous FORTEO (20 μg daily), both of which were open-label.
The primary endpoint was percentage change from baseline in lumbar spine BMD at 12 months. Secondary endpoints included percentage changes in BMD and in bone turnover markers at other sites.