乌鸦传媒

ORLANDO -- New analyses of pivotal trial data for the osteoporosis drug romosozumab (Evenity) indicate that the product is safe and effective in patients with chronic kidney disease (CKD).

At the here, Paul Miller, MD, presented post-hoc analyses of the , which helped secure romosozumab's approval in April 2019 for osteoporotic women at high risk of fracture, multiple risks for fractures, and/or failures with other treatments, looking at the subgroup with CKD. (Miller was affiliated with the Denver-area Colorado Center for Bone Research when the analyses were conducted, but left just prior to the meeting.)

Osteoporosis and renal insufficiency are coexisting disease states in a substantial proportion of postmenopausal women, Miller noted. What's more, bisphosphonates are generally contraindicated in patients with even moderate CKD, defined as an estimated glomerular filtration rate (eGFR) of <35 mL/min.

Romosozumab targets sclerostin to support new bone formation.

FRAME was a double-blind, randomized, placebo-controlled study involving 7,180 postmenopausal women with bone mineral density T-scores of –2.5 to –3.5 at the total hip or femoral neck. Patients were either injected subcutaneously once a month with either 210 mg romosozumab or placebo.

At baseline, most patients (88%) had mild or moderate renal insufficiency; 0.3% had severe CKD.

Assessment of the efficacy endpoints included percentage change in BMD from baseline at the lumbar spine, the total hip, and the femoral neck as well as the incidence of new vertebral fractures, adverse events, and any progression of CKD.

By the end of the trial period, changes in BMD were similar irrespective of baseline eGFR. The least squares mean percent change from baseline in BMD was 13.1% (95% CI 12.8%-13.3%) with romosozumab vs 0.4% (95% CI 0.2%–0.5%) for lumbar spine. A similar pattern was seen with total hip and femoral neck BMD.

Regardless of the baseline eGFR, new vertebral fractures were significantly reduced during the 1-year evaluation period. Adverse events during the study were well balanced between drug and placebo groups, also irrespective of CKD staging.

Rates of positive adjudicated major cardiovascular events were also similar across all stages of CKD.

Serum calcium was withdrawn pre-dose every month over a 12-month period. Only one case of hypocalcemia as defined by <8.8 mg/dL was observed in the romosozumab group.

"The safety of romosozumab was generally comparable among eGFR subgroups and therefore romosozumab could be considered a treatment option for osteoporotic patients with mild to moderate chronic kidney disease," Miller said.

He noted, though, that the study enrolled few patients with eGFR less than 30 mL/min and no patients with an eGFR less than 15, so the findings may not apply to patients with the severest renal impairment.

Comment