Overview of the Key Evenity Trials
Evenity (romosozumab) was primarily evaluated in two pivotal Phase 3 studies: the FRAME (Fracture Study in Postmenopausal Women with Osteoporosis) trial and the ARCH (Active-Controlled Fracture Study) trial. These studies formed the basis for Evenity’s approval as a treatment for osteoporosis in high-risk postmenopausal women.
The FRAME study was a double-blind, placebo-controlled trial involving over 7,000 postmenopausal women, examining Evenity followed by an antiresorptive agent compared to placebo followed by the same agent. The ARCH trial was an active-controlled study comparing Evenity followed by alendronate against alendronate alone in over 4,000 women with severe osteoporosis.
Key Efficacy Results: Bone Mineral Density and Fracture Reduction
Evenity's dual-action mechanism, which stimulates bone formation while reducing bone resorption, contributes to its efficacy. Clinical trial data supports this through significant improvements in bone mineral density (BMD) and fracture risk reduction.
Findings from the FRAME Trial
- Significant BMD Increases: After 12 months, Evenity led to significant BMD increases at the lumbar spine, total hip, and femoral neck compared to placebo.
- Reduced Vertebral Fractures: The trial showed a substantial reduction in new vertebral fractures after 12 months with Evenity compared to placebo, sustained through 24 months with follow-up therapy.
Findings from the ARCH Trial
- Superior Fracture Reduction: Evenity followed by alendronate was superior to alendronate alone, showing a lower risk of new vertebral fracture over 24 months.
- Reduced Clinical Fractures: The Evenity group also experienced a relative reduction in clinical fractures over 24 months.
Addressing the Cardiovascular Risk Concern
A significant finding from the ARCH trial was a higher rate of major adverse cardiac events (MACE) in the Evenity group compared to the alendronate group, leading to a boxed warning on Evenity's prescribing information. This imbalance was not seen in the FRAME study. Evenity should not be started in patients with a recent history of heart attack or stroke. Healthcare providers must assess the risks and benefits, especially for patients with cardiovascular risk factors.
Common and Serious Side Effects
Evenity trials reported common side effects like joint pain and headaches. Rare but serious side effects include osteonecrosis of the jaw (ONJ), atypical femoral fractures, and hypocalcemia (low blood calcium). Precautions like dental exams and calcium/vitamin D supplementation are recommended.
Treatment Duration and Follow-Up
Evenity's bone-building effect is primarily seen within the 12-month treatment period. Following this, continued therapy with an antiresorptive agent like denosumab or alendronate is typically recommended to maintain BMD gains.
Evenity vs. Prolia (Denosumab)
Evenity and Prolia are both injectable osteoporosis treatments with different mechanisms. Evenity builds bone and reduces loss, while Prolia mainly slows bone loss. Key differences are summarized in the table below:
| Feature | Evenity (Romosozumab) | Prolia (Denosumab) |
|---|---|---|
| Mechanism | Dual-action: builds new bone and reduces bone loss | Antiresorptive: inhibits RANKL to slow bone breakdown |
| Treatment Duration | Limited to 12 monthly doses | Can be used long-term |
| Administration Frequency | Monthly injections for 1 year | Injections every 6 months |
| Patient Eligibility | Postmenopausal women at high fracture risk | Postmenopausal women, and men, with osteoporosis |
| Cardiovascular Risk | Boxed warning for increased risk in certain populations | Not associated with a boxed warning for increased CV risk |
Conclusion: Interpreting the Evenity Trial Data
What are the results of the evenity trial? Clinical trials demonstrate that Evenity effectively increases bone mineral density and reduces vertebral and clinical fracture risks in high-risk postmenopausal women over a 12-month course. Subsequent treatment with an antiresorptive agent helps preserve these benefits. However, the cardiovascular risk highlighted in the ARCH trial requires careful patient evaluation by a healthcare provider, especially for those with a history of heart attack or stroke. For eligible patients, Evenity offers a powerful, short-term treatment option. For more information, visit the American College of Rheumatology.
