What are the advantages and disadvantages of Tymlos (Abaloparatide) for osteoporosis treatment?

From the Guidelines

Tymlos (abaloparatide) is a recommended treatment option for men with osteoporosis at a very high risk of fracture, due to its ability to stimulate bone formation and reduce fracture risk, as supported by the strongest data with respect to BMD changes 1. The main benefits of Tymlos include significant reduction in vertebral and non-vertebral fracture risk, rapid onset of action, and effectiveness in men with severe osteoporosis. Some key points to consider when prescribing Tymlos include:

• It's administered as a daily subcutaneous injection (80 mcg) for up to 24 months
• Common side effects include dizziness, nausea, headache, palpitations, and injection site reactions
• More concerning is the black box warning about potential osteosarcoma risk, which is why treatment is limited to 2 years maximum lifetime use
• It's contraindicated in patients with bone cancer risk factors, Paget's disease, unexplained elevated alkaline phosphatase, prior radiation therapy involving the skeleton, or hypercalcemia
• Tymlos requires refrigeration, daily injections, and can be expensive without insurance coverage After completing treatment, patients typically transition to an antiresorptive medication like a bisphosphonate to maintain bone density gains. It is essential to weigh the benefits and drawbacks of Tymlos and consider individual patient factors, such as fracture risk and medical history, when making treatment decisions, as recommended by recent guidelines 1. Additionally, other treatment options, such as bisphosphonates and denosumab, may be considered as first-line or second-line treatments, depending on patient-specific factors and guideline recommendations 1.

From the FDA Drug Label

TYMLOS is indicated for the treatment of postmenopausal women with osteoporosis at high risk for fracture, or patients who have failed or are intolerant to other available osteoporosis therapy In postmenopausal women with osteoporosis, TYMLOS reduces the risk of vertebral fractures and nonvertebral fractures. The safety and efficacy of TYMLOS have not been evaluated beyond 2 years of treatment. Abaloparatide caused a dose-dependent increase in the incidence of osteosarcoma in male and female rats after subcutaneous administration at exposures 4 to 28 times the human exposure at the clinical dose of 80 mcg It is unknown whether TYMLOS will cause osteosarcoma in humans.

The advantages of Tymlos (Abaloparatide) for osteoporosis treatment are:

• Reduces the risk of vertebral fractures and nonvertebral fractures in postmenopausal women with osteoporosis
• Increases bone density in men with osteoporosis at high risk for fracture

The disadvantages of Tymlos (Abaloparatide) for osteoporosis treatment are:

• May cause osteosarcoma, although it is unknown whether this risk applies to humans
• Should not be used for more than 2 years during a patient's lifetime due to lack of safety and efficacy data beyond this duration
• May cause hypercalcemia, orthostatic hypotension, and hypersensitivity reactions 2, 2

From the Research

Advantages of Tymlos (Abaloparatide) for Osteoporosis Treatment

• Increased bone mineral density and reduced fracture risk in post-menopausal women, as demonstrated in the ACTIVE study and its extension ACTIVExtend 3, 4
• Effective in mitigating or preventing bone loss from ovariectomy, orchiectomy, and glucocorticoids, and improving fracture healing, as shown in preclinical studies 3
• Reduced risk of vertebral, nonvertebral, major osteoporotic, and clinical fractures compared with placebo, as seen in the Abaloparatide Comparator Trial In Vertebral Endpoints (ACTIVE) study 5, 6, 7
• Improved cost effectiveness compared with teriparatide, due to reduced prevalence of hypercalcemia and lower cost of the marketed compound 5
• Sustained therapeutic effects with subsequent alendronate therapy, as demonstrated in the ACTIVExtend study 4

Disadvantages of Tymlos (Abaloparatide) for Osteoporosis Treatment

• Higher occurrence of adverse effects, such as palpitations and increased heart rate, compared with teriparatide, which may lead to discontinuation of treatment 5, 4
• Discontinuations due to dizziness, nausea, and headache were slightly more common in abaloparatide-treated patients, as seen in the ACTIVE study 4
• Potential concerns regarding the safety and efficacy of abaloparatide in certain subpopulations, such as women with various baseline risk factors, although post hoc analyses have supported its efficacy and safety in these groups 4, 7