Evaluator’s overall conclusions on clinical safety The safety data seen in the pivotal study in men with osteoporosis was similar to that seen previously in studies in postmenopausal women with osteoporosis. The long term studies in postmenopausal women with osteoporosis did not identify any additional risks with the exception of the cases of osteonecrosis of the jaw. While the patients who developed these events also had local risk factors the incidence is significant and should be better reflected in the Product Information. The post-marketing review of adverse events states that there is sufficient evidence to add drug sensitivity as a post marketing adverse drug reactions to the national product labelling. This is not reflected in the proposed Product Information included in the submission. First round benefit-risk assessment First round assessment of benefits The benefits of Prolia in the proposed usage are: Increase in BMD at all skeletal measured: lumbar spine, proximal femur (total hip, femoral neck, trochanter), and distal radius compared with placebo at 12 months. The magnitudes of the mean BMD increases observed in males with osteoporosis were similar to those observed in studies in postmenopausal women. Increases in BMD were associated with a decrease in new vertebral, non vertebral, and hip fractures in studies in previously evaluated studies (20030216 and 20040138). It is reasonable to extrapolate the same in men with osteoporosis. Safety in men with osteoporosis was similar to that seen in postmenopausal First round assessment of risks The risks of Prolia in the proposed usage are: AEs which are similar to those previously documented for denosumab. Osteonecrosis of the jaw is likely in a small number of subjects with long term use of denosumab. First round assessment of benefit-risk balance The benefit-risk balance of Prolia, given the proposed usage, is favourable. First round recommendation regarding authorisation Based on the clinical data submitted, it is recommended that the application be approved. Clinical questions No clinical questions.
Evaluator’s overall conclusions on clinical safety The safety data seen in the pivotal study in men with osteoporosis was similar to that seen previously in studies in postmenopausal women with osteoporosis. The long term studies in postmenopausal women with osteoporosis did not identify any additional risks with the exception of the cases of osteonecrosis of the jaw. While the patients who developed these events also had local risk factors the incidence is significant and should be better reflected in the Product Information. The post-marketing review of adverse events states that there is sufficient evidence to add drug sensitivity as a post marketing adverse drug reactions to the national product labelling. This is not reflected in the proposed Product Information included in the submission. First round benefit-risk assessment First round assessment of benefits The benefits of Prolia in the proposed usage are: Increase in BMD at all skeletal measured: lumbar spine, proximal femur (total hip, femoral neck, trochanter), and distal radius compared with placebo at 12 months. The magnitudes of the mean BMD increases observed in males with osteoporosis were similar to those observed in studies in postmenopausal women. Increases in BMD were associated with a decrease in new vertebral, non vertebral, and hip fractures in studies in previously evaluated studies (20030216 and 20040138). It is reasonable to extrapolate the same in men with osteoporosis. Safety in men with osteoporosis was similar to that seen in postmenopausal First round assessment of risks The risks of Prolia in the proposed usage are: AEs which are similar to those previously documented for denosumab. Osteonecrosis of the jaw is likely in a small number of subjects with long term use of denosumab. First round assessment of benefit-risk balance The benefit-risk balance of Prolia, given the proposed usage, is favourable. First round recommendation regarding authorisation Based on the clinical data submitted, it is recommended that the application be approved. Clinical questions No clinical questions.
auspar-denosumab-140128-cer.docx