Evenity Adverse Reactions

Summary of the safety profile: In the overall romosozumab (EVENITY) pre-registration clinical programme, 7681 subjects received at least one dose of romosozumab, 6338 subjects received romosozumab for at least 6 months, and 5863 subjects (5712 women and 151 men) received romosozumab for at least 12 months. The safety of romosozumab (EVENITY) described as follows is based on 12-month pooled data from 3695 postmenopausal women with osteoporosis and 163 men with osteoporosis treated with romosozumab in four Phase II and Phase III, placebo-controlled clinical trials, including the FRAME and BRIDGE studies. Of the 7628 subjects who received romosozumab (EVENITY) or placebo in these four studies, 78.4% of subjects in the romosozumab (EVENITY) group and 80.0% of subjects in the placebo group had at least one treatment-emergent adverse event during the double-blind period (see Table 8). Adverse events leading to discontinuation were reported for 3.0% of subjects in the total romosozumab (EVENITY) group and 2.6% of subjects in the placebo group. Adverse events considered treatment-related were reported for 16.1% of subjects in the romosozumab (EVENITY) group and 13.5% of subjects in the placebo group.
At least one serious adverse event was reported for 9.7% of subjects in the total romosozumab (EVENITY) group and 8.9% of subjects in the placebo group. The only serious adverse event occurring in ≥0.5% of subjects in either group was pneumonia (0.5% romosozumab (EVENITY), 0.3% placebo). There were no serious adverse events reported at a ≥2% higher incidence in the total romosozumab (EVENITY) group compared to the placebo group.
In a placebo-controlled phase 2 study in postmenopausal women with low BMD in the lumbar spine, total hip or femoral neck, 51 subjects received 210 mg romosozumab once a month for 24 months (safety analysis set). The proportion of subjects reporting adverse events, serious adverse events and adverse events leading to discontinuation was similar between the romosozumab (EVENITY) and placebo groups.
The adverse reactions in romosozumab-treated patients (n=2040) in a separate double-blind, Phase III active-controlled study (ARCH) were similar in type to those seen in the placebo-controlled trials. The most common adverse reactions (≥1/10) from the pooled safety data were viral upper respiratory tract infection and arthralgia.
Tabulated list of adverse events: Adverse events occurring in patients treated with romosozumab at an incidence rate ≥2.0% in placebo-controlled clinical trials are shown in Table 8. (See Table 8.)

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Adverse reactions: Adverse reactions occurring in patients treated with romosozumab in clinical trials are shown by system organ class and frequency in Table 9. (See Table 9.)

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Immunogenicity: As with all therapeutic proteins, there is potential for immunogenicity. The immunogenicity of romosozumab has been evaluated using a screening immunoassay for the detection of binding anti-romosozumab antibodies. For patients whose sera tested positive in the screening immunoassay, an in vitro biological assay was performed to detect neutralising antibodies.
In postmenopausal women dosed with 210 mg monthly romosozumab (EVENITY), the incidence of anti-romosozumab antibodies was 18.1% (1072 of 5914) for binding antibodies and 0.8% (50 of 5914) for neutralising antibodies. Across all doses studied in postmenopausal women, the pooled incidence of binding antibodies and neutralising antibodies was similar to the 210 mg monthly dose, respectively. In men with osteoporosis dosed with 210 mg monthly romosozumab (EVENITY), the incidence of anti-romosozumab antibodies was consistent [17.3% (28 of 162) for binding antibodies and 0.6% (1 of 161) for neutralising antibodies] with that observed in postmenopausal women with osteoporosis. The clinical significance of antibodies to romosozumab is unknown. No impact to the efficacy and safety of romosozumab was observed in the presence of anti-romosozumab antibodies.
Withdrawal effects: In the absence of a follow-on antiresorptive therapy, BMD gains trend toward pre-treatment levels following cessation of romosozumab (EVENITY). The effect on BMD following the discontinuation of romosozumab was prospectively studied in a phase 2 dose-ranging study (Study 20060326) where romosozumab was given for longer duration than the approved posology. After romosozumab completion, BMD levels across measured sites trended towards pre-treatment levels but remained above baseline over a 12 month period.
Post-marketing experience: Not applicable at this time.
Reporting suspected adverse effects: Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions.