Evenity - Drug Monograph

Introduction

Evenity (romosozumab-aqqg) is a novel bone-forming monoclonal antibody approved for the treatment of osteoporosis in postmenopausal women at high risk for fracture. Developed by Amgen and UCB Pharma, Evenity represents a significant advancement in osteoporosis management with its unique dual mechanism of action that both builds new bone and reduces bone resorption.

Mechanism of Action

Evenity is a sclerostin inhibitor that works through a dual mechanism. It binds to sclerostin, a natural inhibitor of bone formation produced by osteocytes. By inhibiting sclerostin, Evenity:

• Increases bone formation by activating Wnt signaling pathway
• Decreases bone resorption by reducing osteoclast activity

This dual action results in rapid and substantial increases in bone mineral density (BMD)

Indications

FDA-approved for the treatment of osteoporosis in postmenopausal women at high risk for fracture, defined as:

• History of osteoporotic fracture
• Multiple risk factors for fracture
• Patients who have failed or are intolerant to other available osteoporosis therapy

Dosage and Administration

• Dosage: 210 mg administered monthly
• Route: Subcutaneous injection
• Treatment duration: 12 months total therapy
• Administration: Two consecutive 105 mg injections (total 210 mg) administered once monthly
• Special populations: No dosage adjustment required for renal or hepatic impairment

Pharmacokinetics

• Absorption: Bioavailability approximately 70-80% following subcutaneous administration
• Distribution: Volume of distribution approximately 3.9 L; limited tissue distribution
• Metabolism: Degraded via proteolytic enzymes throughout the body (typical of monoclonal antibodies)
• Elimination: Half-life approximately 5-7 days; cleared via intracellular catabolism
• Time to peak concentration: 5 days post-dose

Contraindications

• Hypersensitivity to romosozumab or any component of the formulation
• Hypocalcemia (must be corrected prior to initiation)
• History of myocardial infarction or stroke within the preceding year

Warnings and Precautions

Drug Interactions

• Calcium supplements: May reduce absorption of oral calcium supplements; separate administration by at least 30 minutes
• Vitamin D supplements: No significant interactions, but essential for proper calcium absorption
• Other osteoporosis therapies: Sequential therapy with antiresorptive agents recommended after 12-month course

Adverse Effects

• Arthralgia (13%)
• Headache (8%)
• Injection site reactions (5%)

• Cardiovascular events (myocardial infarction, stroke)
• Hypocalcemia
• Osteonecrosis of the jaw
• Atypical femoral fractures
• Allergic reactions (anaphylaxis, angioedema)

Monitoring Parameters

• Baseline: Serum calcium, 25-hydroxyvitamin D, renal function, cardiovascular risk assessment
• During treatment: Serum calcium within 2 weeks after initiation and periodically
• Bone mineral density: Assess at 12 months using DXA scan
• Cardiovascular monitoring: Regular assessment of cardiovascular status
• Dental health: Regular oral examinations
• Symptom monitoring: Thigh/groin pain, jaw pain/numbness

Patient Education

• Complete the full 12-month treatment course as prescribed
• Maintain adequate calcium (1200 mg daily) and vitamin D (800-1000 IU daily) intake
• Report any chest pain, shortness of breath, or neurological symptoms immediately
• Inform all healthcare providers about Evenity treatment, especially before dental procedures
• Be aware of potential signs of low calcium (muscle spasms, numbness, tingling)
• Do not receive more than 12 months of treatment
• Understand that follow-up antiresorptive therapy will likely be necessary

References

1. FDA Prescribing Information: Evenity (romosozumab-aqqg). 2019 2. Cosman F, et al. Romosozumab Treatment in Postmenopausal Women with Osteoporosis. N Engl J Med. 2016;375(16):1532-1543 3. Saag KG, et al. Romosozumab or Alendronate for Fracture Prevention in Women with Osteoporosis. N Engl J Med. 2017;377(15):1417-1427 4. McClung MR, et al. Romosozumab in Postmenopausal Women with Low Bone Mineral Density. N Engl J Med. 2014;370(5):412-420 5. Miller PD, et al. Effect of Abaloparatide vs Placebo on New Vertebral Fractures in Postmenopausal Women with Osteoporosis. JAMA. 2016;316(7):722-733