nsitivity reactions were reported in 364 (6.5%) women in the EVENITY groupand 365 (6.5%) women in the control group. Reported reactions included angioedema (3 women [< 0.1%]in the EVENITY group vs. 3 [< 0.1%] women in the control group), erythema multiforme (1 woman[< 0.1%] in the EVENITY group vs. no woman in the control group), dermatitis (32 women [0.6%] in theEVENITY group vs. 42 women [0.8%] in the control group), rash (60 women [1.1%] in the EVENITYgroup vs. 53 women [0.9%] in the control group), and urticaria (23 women [0.4%] in the EVENITYgroup vs. 27 women [0.5%] in the control group). Although angioedema, dermatitis and urticaria were notreported at a higher incidence with EVENITY than control, there were cases of angioedema, dermatitisand urticaria that were determined to be related to EVENITY use [see Contraindications (4) andWarnings and Precautions (5.2)].
Hypocalcemia
Across both trials, adverse events of hypocalcemia occurred in 2 EVENITY-treated women and in 1oman in the control group. Decreases in albumin-adjusted serum calcium to below the lower limit of thereference range (8.3 mg/dL) were reported in 14 (0.2%) women in the EVENITY group and 10 (0.2%)women in the control group. No patient receiving EVENITY developed serum calcium lessthan 7.5 mg/dL. The nadir in albumin-adjusted serum calcium occurred by month 1 after EVENITYdosing in patients with normal renal function [see Contraindications (4) and Warnings andPrecautions (5.3)].
Injection Site Reactions
Across both trials, injection site reactions occurred in 278 (4.9%) women in the EVENITY group and 157(2.8%) women in the control group. The most common injection site reactions were pain (94 [1.7%]women in the EVENITY group; 70 [1.3%] in the control group) and erythema (80 [1.4%] women in theEVENITY group and 14 [0.3%] women in the control group). Injection site reactions resulted indiscontinuation of treatment in 7 (0.1%) EVENITY-treated patients and 3 (< 0.1%) patients in the control
group.
Osteonecrosis of the Jaw
Across both trials, osteonecrosis of the jaw occurred in one patient during treatment with EVENITY. [seeWarnings and Precautions (5.4)].
Atypical Subtrochanteric and Diaphyseal Fractures
Across both trials, atypical femoral fracture occurred in one patient during treatment with EVENITY [seeWarnings and Precautions (5.5)].
6.2 Immunogenicity
As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibodyformation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observedincidence of antibody (including neutralizing antibody) positivity in an assay may be influenced byseveral factors, including assay methodology, sample handling, timing of sample collection, concomitantmedications, and underlying disease. For these reasons, comparison of the incidence of antibodies in thestudies described below with the incidence of antibodies in other studies or to other romosozumabproducts may be misleading.
The immunogenicity of EVENITY was eva luated using an immunoassay for the detection ofanti-romosozumab-aqqg antibodies. An in vitro biological assay was performed to detect neutralizingantibodies for those subjects whose sera tested positive for anti-romosozumab-aqqg antibodies.
Among 5914 postmenopausal women treated with EVENITY 210 mg monthly, 18.1% of subjectsdeveloped antibodies to romosozumab-aqqg. Of the subjects who developed antib |
