Regulatory Approval and Clinical Evidence for Evenity in Men
Evenity, the brand name for the drug romosozumab, is a powerful bone-building medication used to treat osteoporosis. However, the approved patient population varies by country. While the U.S. Food and Drug Administration (FDA) has restricted its approved indication to postmenopausal women, regulatory bodies in other parts of the world have extended its use to men with osteoporosis. This variation highlights the differing interpretations of clinical trial data and risk-benefit profiles across global health authorities.
International Approvals for Evenity in Men
- Australia: The Australian Therapeutic Goods Administration (TGA) has approved Evenity for treating osteoporosis in both postmenopausal women and men.
- Japan: The Japanese Ministry of Health, Labor and Welfare granted marketing authorization for Evenity for both men and postmenopausal women with osteoporosis who are at a high risk of fracture. This decision was based on the successful outcomes of clinical trials involving male patients.
- United States: The FDA approval for Evenity is limited to postmenopausal women at high risk of fracture. This is primarily because the Phase 3 clinical trial in men, known as BRIDGE, did not count the number of fractures, making it unclear if Evenity reduces fracture risk in this population, despite showing bone mineral density increases.
- United Kingdom: In the UK, Evenity is licensed only for use in women who have been through menopause, though off-label use is possible under a doctor's discretion.
Clinical Trial Data: The BRIDGE Study
One of the key studies supporting the use of Evenity in men is the Phase 3 BRIDGE study.
- Study Population: The trial included 245 men aged 55 to 90 with low bone mineral density and a history of fragility fractures.
- Study Design: The men were randomized to receive either Evenity or a placebo, in addition to daily calcium and vitamin D supplements, for 12 months.
- Key Finding: After 12 months, the Evenity group showed a significant increase in bone mineral density (BMD) at the lumbar spine and total hip compared to the placebo group. Specifically, there was a 12% increase in BMD at the spine for the Evenity group, versus only a 1% increase for the placebo group.
- Limitations: A notable limitation of the BRIDGE study is that it did not have fracture reduction as a primary endpoint, focusing instead on BMD changes.
Comparison of Treatment Options for Male Osteoporosis
While Evenity may be used in men in some countries, it is not the only option. In the U.S., other FDA-approved treatments for male osteoporosis exist. Choosing the right medication depends on several factors, including the patient's fracture risk, cardiovascular health, and tolerance for potential side effects.
| Feature | Evenity (Romosozumab) | Prolia (Denosumab) | Bisphosphonates (e.g., Alendronate) |
|---|---|---|---|
| FDA Approval (Men) | No | Yes | Yes (e.g., Alendronate) |
| Mechanism of Action | Blocks sclerostin to increase bone formation and decrease bone resorption | Blocks RANKL to inhibit bone resorption | Inhibit osteoclast activity to reduce bone resorption |
| Administration | Subcutaneous injection, 12 monthly doses | Subcutaneous injection every 6 months | Oral tablets (daily or weekly) or IV infusion |
| Duration of Use | Limited to 12 monthly doses | No recommended limit on duration | Typically 3-5 years |
| Transition Therapy | Required after 12 months to maintain gains (e.g., Prolia, Alendronate) | Not applicable | Considered after 3-5 years to assess risk |
| Cardiovascular Risk | Black box warning: increased risk of heart attack, stroke, and cardiovascular death | No black box warning related to cardiovascular events | Generally not associated with increased cardiovascular risk |
| Post-Treatment Effects | Bone density gains wane without follow-on therapy | Rebound effect with increased fracture risk if stopped without transition | Gains are largely maintained for some time after stopping |
Evenity Use in Men: The Off-Label Possibility
Given the evidence from clinical trials and international approvals, some U.S. physicians may consider prescribing Evenity off-label for male osteoporosis, particularly in cases of very high fracture risk. Off-label use means prescribing a medication for a condition or population not specifically approved by the FDA. This decision would require careful consideration and a thorough discussion between the patient and their doctor, especially concerning the cardiovascular risks associated with Evenity.
What to Consider for Off-Label Use
- Patient History: The patient's risk profile, including any history of recent heart attack or stroke, is a critical factor.
- Insurance Coverage: Because it is not FDA-approved for men, insurance coverage for off-label use is not guaranteed and can be a significant hurdle.
- Weighing Risks and Benefits: For some men with a very high fracture risk who have failed other treatments, the potential bone-building benefit might outweigh the cardiovascular risk, but this is a complex and individualized decision.
Conclusion
While Evenity has been shown to increase bone mineral density in clinical trials involving men, its approved use in this population is not universal. The U.S. FDA has not approved Evenity for male osteoporosis, unlike regulatory bodies in Australia and Japan. For men in the U.S., this means that Evenity is not a standard treatment option, and other therapies like bisphosphonates and Prolia are typically used. However, off-label use might be considered for high-risk individuals after a careful assessment of risks and benefits with a healthcare provider. The decision to use Evenity in men is nuanced, dependent on geographical regulations, individual patient health, and the specific clinical trial data available to a physician.
What to Do After a Course of Evenity
For patients who do complete a 12-month course of Evenity, whether through approved or off-label use, it is crucial to transition to an antiresorptive therapy, such as Prolia or a bisphosphonate. The bone-building effects of Evenity diminish after the 12-month period, and without follow-on therapy, bone density gains can be lost. This subsequent treatment helps lock in and maintain the new bone mass built by Evenity, ensuring long-term protection against fractures.
