Indications for: EVENITY
In postmenopausal women with osteoporosis: at high risk for fracture, defined as a history of osteoporotic fracture, or multiple risk factors for fracture; or patients who have failed or are intolerant to other therapy.
Limitations of Use:
Duration limited to 12 monthly doses; consider anti-resorptive agent if continued therapy for osteoporosis warranted.
Study 1 (ClinicalTrials.gov: NCT01575834):
A randomized, double-blind, placebo-controlled study of postmenopausal women aged 55 to 90 years (mean age of 71 years) with bone mineral density (BMD) T-score less than or equal to -2.5 at the total hip or femoral neck.
Women were randomized to receive subcutaneous injections of either Evenity (N=3589) or placebo (N=3591) for 12 months, with 500 to 1000 mg calcium and 600 to 800 international units vitamin D supplementation daily. At baseline, 18% of women had a vertebral fracture. After the 12-month treatment period, women in both arms transitioned to open-label anti-resorptive therapy (denosumab) for 12 months while remaining blinded to their initial treatment.
The coprimary efficacy endpoints were new vertebral fracture at month 12 and month 24.
Effect on Fractures
- Evenity significantly reduced the incidence of new vertebral fractures through month 12 compared to placebo (0.5% vs 1.8%; P <.001, respectively). In addition, the significant reduction in fracture risk persisted through the second year in women who received Evenity during the first year and transitioned to denosumab compared to those who transitioned from placebo to denosumab (0.6% vs 2.5%; P <.001, respectively).
- Evenity significantly reduced the incidence of clinical fracture (a composite endpoint of symptomatic vertebral fracture and nonvertebral fracture) at 12 months. However, 88% of these clinical fractures were nonvertebral fractures and the incidence of nonvertebral fractures was not statistically significantly different when comparing Evenity-treated women to placebo-treated women at month 12 or month 24.
Effect on Bone Mineral Density (BMD)
- Evenity significantly increased BMD at the lumbar spine, total hip, and femoral neck compared with placebo at month 12. The treatment differences in BMD were 12.7% at the lumbar spine, 5.8% at the total hip, and 5.2% at the femoral neck.
Study 2 (ClinicalTrials.gov: NCT01631214):
A randomized, double-blind, alendronate-controlled study of postmenopausal women aged 55 to 90 years (mean age of 74 years) with BMD T-score less than or equal to -2.5 at the total hip or femoral neck and either one moderate or severe vertebral fracture or two mild vertebral fractures, or BMD T-score less than or equal to -2.0 at the total hip or femoral neck and either two moderate or severe vertebral fractures or a history of a proximal femur fracture.
Women were randomized (1:1) to receive either monthly subcutaneous injections of Evenity (N=2046) or oral alendronate 70 mg weekly (N=2047) for 12 months, with 500 to 1000 mg calcium and 600 to 800 international units vitamin D supplementation daily. After the 12-month treatment period, women in both arms transitioned to open-label alendronate 70 mg weekly while remaining blinded to their initial treatment.
This was an event driven trial. The two primary efficacy endpoints were the incidence of morphometric vertebral fracture at 24 months and time to the first clinical fracture through the primary analysis period, which ended when at least 330 patients had a clinical fracture and all patients had completed the 24-month visit. Clinical fracture was a composite endpoint of nonvertebral fracture and symptomatic vertebral fracture. The median duration of follow-up for the primary analysis period was 33 months.
Effect on Fractures
- Evenity significantly reduced the incidence of new vertebral fracture at 24 months compared to alendronate alone (4.1% vs 8.0%; P <.001, respectively).
- Evenity significantly reduced the risk of clinical fracture through the end of the primary analysis period compared to alendronate alone (9.7% vs 13.0%, respectively), with a hazard ratio of 0.73 (95% CI, 0.61-0.88; P <.001).
- Evenity followed by alendronate also significantly reduced the risk of nonvertebral fracture through the primary analysis period (median follow-up of 33 months), with a hazard ratio of 0.81 (95% CI, 0.66-0.99; P =0.04) compared to alendronate alone.
Effect on Bone Mineral Density (BMD)
- Evenity significantly increased BMD at the lumbar spine, total hip, and femoral neck compared with alendronate at month 12. The treatment differences in BMD were 8.7% at the lumbar spine, 3.3% at the total hip, and 3.2% at the femoral neck.
Should be administered by a healthcare professional. Give as SC inj in abdomen, thigh or upper arm; rotate inj sites. 210mg once monthly (given as 2 separate syringes consecutively) for 12 months. Supplement with calcium and Vit.D during treatment.
Potential risk of myocardial infarction, stroke and cardiovascular death.
Increased risk of major adverse cardiac events; monitor. MI or stroke within previous year: do not initiate. Discontinue if MI, stroke, anaphylaxis, other hypersensitivity reaction occurs. Correct hypocalcemia prior to initiating; monitor for signs/symptoms. Monitor for osteonecrosis of the jaw (ONJ). Do baseline oral exam if risks for ONJ exist (eg, tooth extraction, oral surgery, poor oral hygiene, and/or other pre-existing dental disease, infection, cancer, radiotherapy, anemia, coagulopathy); discontinue based on risk/benefit assessment. Maintain good oral hygiene. Evaluate for atypical fractures if thigh/groin pain develops; consider interrupting therapy based on risk/benefit assessment. Do not inj areas where skin is tender, bruised, red, hard, or scars or stretch marks. Severe renal impairment or on dialysis: monitor serum calcium and adequately supplement with Vit.D and calcium. Women of reproductive potential, pregnancy, nursing mothers: not indicated.
Increased risk of ONJ with concomitant corticosteroids, chemotherapy, bisphosphonates, angiogenesis inhibitors or denosumab.
Arthralgia, headache, muscle spasms, peripheral edema, asthenia, neck pain, insomnia, paresthesia; hypersensitivity, atypical subtrochanteric and diaphyseal femoral fractures.
The mean effective half-life was 12.8 days after 3 doses of 3 mg/kg (the approved recommended dosage for a 70 kg woman) every 4 weeks.
Generic Drug Availability:
Single-use prefilled syringes—2