EVENITY (romosozumab)

Key points

Favourable opinion for reimbursement in the treatment of severe postmenopausal osteoporosis only in women aged < 75 years with a history of severe fracture and in the absence of a history of coronary heart disease.

Unfavourable opinion for reimbursement in women with postmenopausal osteoporosis aged ≥ 75 years or < 75 years with a history of coronary heart disease.

What therapeutic improvement?

No clinical added value in the therapeutic strategy on the basis of currently available data.

Role in the care pathway?

The aim of osteoporosis treatment is to prevent the occurrence of fractures by reinforcing the solidity (or resistance) of bone tissue and by preventing falls.

The treatment decision is based on the fracture risk, which depends on the existence of a history of fracture due to bone fragility and the bone mineral density (BMD), as well as other risk factors.

Before any specific treatment is prescribed, any vitamin D and/or calcium deficiency should be corrected (particularly in the oldest patients), by adjusting dietary intake and/or medicinal supplementation. In addition, physical exercise and fall prevention are part of the overall management strategy for osteoporosis patients.

Medicinal fracture-prevention treatment is indicated only in the event of a high fracture risk (a BMD with a T-score < -2.5 but greater than - 3 is not sufficient to decide to initiate treatment). Patients with a high fracture risk are defined as those having had a fracture due to bone fragility or, in the absence of a fracture, patients with a marked reduction in bone density (T score < - 3) or with a T score ≤ - 2.5 combined with other fracture risk factors, in particular age > 60 years, previous or current systemic corticosteroid therapy at a dosage ≥ 7.5 mg/day of prednisone equivalent, a BMI < 19 kg/m², a history of femoral neck extremity fracture in a first-degree relative, an early menopause (before the age of 40 years).

The care pathway in postmenopausal osteoporosis (PMO) is described in Annex 2.

In women with severe postmenopausal osteoporosis with a history of severe fracture, the recommended treatments are:

• bisphosphonates (zoledronate, alendronate, risedronate),
• denosumab, only during second-line therapy as follow-on treatment after bisphosphonates,
• and teriparatide, only in women having had at least two vertebral fractures.

In women aged under 70 years, with no venous thromboembolism risk factors, with spinal osteoporosis, at low risk of femoral neck fracture (absence of the following risk factors: femoral T-score < - 3, high fall risk, history of non-vertebral fracture), raloxifen may also be used to reduce the vertebral fracture risk.

Role of the medicinal product in the care pathway

Considering:

• demonstration of the superiority of EVENITY (romosozumab) treatment, administered for 12 months followed by alendronate compared to alendronate alone, on the fracture risk (vertebral fractures, clinical fractures and non-vertebral fractures) in women with severe osteoporosis and a history of severe fracture during first-line treatment (ARCH study),
• demonstration of the superiority of EVENITY (romosozumab) compared to teriparatide, only in terms of BMD (interim endpoint), in women previously treated with bisphosphonates, i.e. from the second line of treatment (STRUCTURE study),
• uncertainties concerning the safety due to higher risks of death and serious cardiovascular events (myocardial infarction and stroke) demonstrated in women treated with romosozumab in the ARCH study,
• but subgroup analyses suggesting a reduction in the absolute risk in women aged < 75 years and in women with no history of myocardial infarction/stroke or coronary heart disease (including revascularisations and hospitalisations for unstable angina) as well as safety results contradicting those of the FRAME study (placebo-controlled, conducted in younger women with less severe osteoporosis), which did not find any difference between the groups.

The Transparency Committee considers that, on the basis of currently available data, the proprietary medicinal product EVENITY (romosozumab) is a new therapeutic option to be used only in postmenopausal women aged < 75 years with severe osteoporosis and a history of severe fracture and in the absence of a history of coronary heart disease (including revascularisations and hospitalisations for unstable angina).

In view of the available data demonstrating an excess risk of mortality and serious cardiovascular events in women aged ≥ 75 years or with a history of coronary heart disease, EVENITY (romosozumab) has no role in the care pathway for these patients.

The Committee reiterates that this treatment is contraindicated in women with a history of myocardial infarction and stroke and highlights the importance of assessing the cardiovascular risk factors before initiating treatment (in particular, hypertension, hyperlipidaemia, diabetes, smoking, severe renal impairment, etc.). If in doubt, a cardiological opinion should be sought.

In accordance with the SPC for EVENITY (romosozumab), the Committee also reiterates that:

• treatment discontinuation should be followed by a switch to bisphosphonates,
• prescription is reserved for osteoporosis treatment specialists.

Special recommendations

The Committee reiterates that this treatment is contraindicated in women with a history of myocardial infarction and stroke and highlights the importance of assessing the cardiovascular risk factors before initiating treatment (in particular, hypertension, hyperlipidaemia, diabetes, smoking, severe renal impairment, etc.). If in doubt, a cardiological opinion should be sought.

In accordance with the SPC for EVENITY (romosozumab), the Committee also reiterates that:

•  treatment discontinuation should be followed by a switch to bisphosphonates,
• prescription is reserved for physicians specialised in osteoporosis treatment.