The results from a phase 2 trial evaluating Romosozumab in postmenopausal women with low bone mineral density ( BMD ) were 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 Alendronate ( Fosamax ) and Teriparatide ( Forteo / Forsteo ).
In this 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 less than 0.001 ).
The largest increases were observed with the Romosozumab 210 mg once-monthly dose, with mean increases compared with baseline, of 11.3% at the lumbar spine, 4.1% at the total hip and 3.7% 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% at the lumbar spine compared to increases of 4.1% and 7.1% at the same region achieved with Alendronate and Teriparatide, respectively. At the total hip, Romosozumab treatment increased BMD 4.1%, while observed gains with Alendronate were 1.9% and with Teriparatide were 1.3% ( all p less than 0.001 ).
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.
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 less than or equal to -2.0 at the lumbar spine, total hip or femoral neck and greater than or equal to -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 Alendronate ( 70 mg weekly ) or subcutaneous Teriparatide ( 20 mcg 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.
Romosozumab is an investigational bone-forming agent. By inhibiting the protein sclerostin, Romosozumab is designed to increase bone formation and decrease bone breakdown. ( Xagena )
Source: UCB & Amgen, 2014