Evenity® (Romosozumab)

Who Should Receive Evenity?

• Postmenopausal women with osteoporosis at high fracture risk
• Those who have failed or are intolerant to other osteoporosis therapies
• Patients with recent osteoporotic fractures or very low bone mineral density (T-score ≤ -2.5)
• Patients without recent cardiovascular events (no MI or stroke within 12 months)

Treatment Duration

12 monthly doses (complete course then transition to antiresorptive therapy).

The 12-month limitation is based on:

• Clinical trial design: Pivotal trials used a 12-month romosozumab course followed by antiresorptive therapy
• Regulatory safety concerns: Cardiovascular event signals prompted conservative approval with a fixed 12-month course
• Treatment strategy: Romosozumab is an anabolic "bone builder" intended as a finite course to rapidly increase BMD, after which antiresorptive therapy is recommended to maintain gains

Main Safety Concern

Potential increased risk of myocardial infarction, stroke, and cardiovascular death—boxed warning. Do not start in patients with MI or stroke within the prior year.

Dual Mechanism

• Increased bone formation: By inhibiting sclerostin, Evenity removes the brake on the Wnt signaling pathway, stimulating osteoblasts to build new bone
• Decreased bone resorption: Sclerostin inhibition also reduces RANKL production, which suppresses osteoclast activity and bone breakdown

This dual action leads to rapid gains in bone mineral density (BMD) and fracture risk reduction.

1. Clinical Trial Design

Pivotal trials (FRAME and ARCH) used a 12-month romosozumab course followed by antiresorptive therapy. Efficacy and safety data are based on that regimen.

2. Regulatory Safety Concerns

Trials showed a numerical imbalance in cardiovascular events prompting a boxed warning and conservative approval with a fixed 12-month course to limit potential long-term cardiovascular exposure. Ongoing post-marketing studies continue to evaluate CV risk.

3. Treatment Strategy

Romosozumab is an anabolic "bone builder" intended as a finite course to rapidly increase BMD, after which antiresorptive therapy (e.g., bisphosphonate or denosumab) is recommended to maintain gains.

4. Pharmacological Rationale: The Anabolic Effect Plateaus

Clinical data show that the powerful bone-building (anabolic) effect of romosozumab peaks at approximately 12 months. Bone formation markers (P1NP) peak within the first 2-3 months and return to baseline by month 9-12, despite continued dosing.

Beyond 12 months, the drug's action shifts to be predominantly anti-resorptive, and continuing it does not provide additional significant BMD gains compared to transitioning to a dedicated antiresorptive agent.

Primary Endpoint (12 Months)

• New vertebral fractures: 73% relative risk reduction vs. placebo
• Clinical fractures: 36% relative risk reduction
• BMD gains: Lumbar spine +13.3%, Total hip +6.9%, Femoral neck +5.9%

Reference: Cosman F, Crittenden DB, Adachi JD, et al. Romosozumab Treatment in Postmenopausal Women with Osteoporosis. N Engl J Med. 2016;375(16):1532-1543. PubMed: 27641143

Sequential Therapy Benefit (24 Months)

When Evenity (12 months) was followed by denosumab (12 months), the sequence resulted in a 75% reduction in vertebral fracture risk at 24 months compared to placebo → denosumab, confirming that BMD gains are maintained by subsequent antiresorptive therapy.

Reference: Cosman F, Crittenden DB, Adachi JD, et al. Romosozumab Treatment in Postmenopausal Women with Osteoporosis. N Engl J Med. 2016;375(16):1532-1543. NEJM: 10.1056/NEJMoa1607948

Active-Controlled Trial (vs. Alendronate)

• New vertebral fractures at 24 months: 48% reduction vs. alendronate
• Clinical fractures: 27% reduction
• Non-vertebral fractures: 19% reduction
• Demonstrated superior BMD gains compared to alendronate in the first 12 months

Reference: Saag KG, Petersen J, Brandi ML, et al. Romosozumab or Alendronate for Fracture Prevention in Women with Osteoporosis. N Engl J Med. 2017;377(15):1417-1427. NEJM: 10.1056/NEJMoa1708322

Pre-Treatment Assessment

• Assess CV risk before prescribing; avoid initiation if MI/stroke in prior year
• Baseline serum calcium and vitamin D levels (correct deficiencies before starting)
• Bone mineral density assessment (DEXA scan)
• Dental examination and clearance
• Renal function assessment (eGFR)

During Treatment

• Complete all 12 doses and plan immediate transition to an antiresorptive to preserve BMD gains
• Monitor calcium, injection site, and any cardiac symptoms
• Ensure adequate calcium (≥500 mg/day) and vitamin D (≥600 IU/day) supplementation
• Report new or unusual thigh, hip, or groin pain (atypical femoral fracture)
• Report chest pain, shortness of breath, or neurological symptoms immediately

Post-Treatment Transition

Critical: There should be no gap between the last dose of Evenity and the initiation of the antiresorptive agent.

• Prolia: Administer first 60 mg dose within 1-2 weeks of final Evenity injection; repeat every 6 months
• Alternative: Alendronate 70 mg weekly or other antiresorptive if Prolia contraindicated
• Continuous therapy prevents rebound bone resorption and maintains BMD gains

Which health plans does CarePoint Infusion Center have contracts with?

Most insurances, including Medicare, Medicaid, UnitedHealthcare, Cigna, Aetna, CareSource, Humana, and Molina.

Does CarePoint Infusion Center work closely with Evenity and Amgen, Inc?

Yes. CarePoint Infusion Center works with Evenity and offers: Pharmaceutical Patient Assistance Program and REMS support.

Does CarePoint Infusion Center offer services for Evenity patients?

Yes. CarePoint Infusion Center offers the following for Evenity patients: counseling and education, insurance assistance, and collecting and understanding practice-specific needs through the voice of the customer.