General Information

Tymlos (abaloparatide) is a human parathyroid hormone-related peptide [PTHrP(1-34)] analog.

Tymlos is specifically indicated for the treatment of postmenopausal women and in men with osteoporosis at high risk for fracture defined as a history of osteoporotic fracture, multiple risk factors for fracture, or patients who have failed or are intolerant to other available osteoporosis therapy.

Tymlos is supplied as an injection for subcutaneous injection. The recommended dosage of Tymlos is 80 mcg subcutaneously once daily. Cumulative use of Tymlos and parathyroid hormone analogs (e.g., teriparatide) for more than two years during a patient’s lifetime is not recommended. Patients should receive supplemental calcium and vitamin D if dietary intake is inadequate. 

Mechanism of Action

Tymlos (abaloparatide) is a human parathyroid hormone-related peptide [PTHrP(1-34)] analog, which acts as an agonist at the PTH1 receptor (PTH1R). This results in activation of the cAMP signaling pathway in target cells. In rats and monkeys, abaloparatide had an anabolic effect on bone, demonstrated by increases in BMD and bone mineral content (BMC) that correlated with increases in bone strength at vertebral and/or nonvertebral site.

Adverse effects associated with the use of Tymlos may include, but are not limited to, the following:

• hypercalciuria
• dizziness
• nausea
• headache
• palpitations
• fatigue
• upper abdominal pain
• vertigo

The Tymlos label comes with the following Black Box Warning: Abaloparatide caused a dose-dependent increase in the incidence of osteosarcoma, a malignant bone tumor, in male and female rats. It is unknown whether Tymlos will cause osteosarcoma in humans. Use of Tymlos is not recommended in patients at increased risk for osteosarcoma. Cumulative use of Tymlos and parathyroid hormone analogs (e.g., teriparatide) for more than two years during a patient’s lifetime is not recommended.

Clinical Trial Results

The FDA approval of Tymlos was based on the results at 18 months from the landmark ACTIVE trial and first six months of ACTIVExtend trial. Subjects were randomized to receive Tymlos 80 mcg (N = 824) or placebo (N = 821) given subcutaneously once daily. Data demonstrated consistent significant and rapid reductions in the risk of vertebral and nonvertebral fractures regardless of age, years since menopause, presence or absence of prior fracture (vertebral or nonvertebral) and bone mineral density (BMD) at baseline. Specifically, in the ACTIVE trial, Tymlos demonstrated significant reductions in the relative risk of new vertebral and nonvertebral fractures compared to placebo: 86 percent in new vertebral fractures and 43 percent in nonvertebral fractures. The absolute risk reductions were 3.6 percent and 2.0 percent, respectively.

The FDA approval of Tymlos in men was based on the Phase 3 ATOM study (Abaloparatide Treatment of Men; BA058-05-019), which was a randomized, double-blind, placebo-controlled, 12-month multicenter study designed to evaluate the efficacy and safety of abaloparatide 80 micrograms in men with osteoporosis. The primary efficacy endpoint of the ATOM study was the percent change from baseline in bone mineral density (BMD) at the lumbar spine at 12 months, which was 8.5% and 1.2% in abaloparatide and placebo groups, respectively. This treatment difference between abaloparatide and placebo was 7.3%.