What is Tymlos (abaloparatide) used for in the treatment of osteoporosis in postmenopausal women and men with high risk of fracture?

What is Tymlos (Abaloparatide)?

Tymlos (abaloparatide) is an FDA-approved anabolic bone-building medication administered as an 80 mcg daily subcutaneous injection for up to 2 years to treat postmenopausal women and men with osteoporosis at high risk for fracture. 1

Mechanism and Drug Class

• Abaloparatide is a synthetic peptide analogue of human parathyroid hormone-related protein (PTHrP) that works by selectively activating the parathyroid hormone type 1 receptor signaling pathway to stimulate new bone formation 2
• Unlike bisphosphonates which prevent bone breakdown, abaloparatide is an osteoanabolic agent that actively builds new bone tissue 3

FDA-Approved Indications

Tymlos is indicated for two specific populations 1:

1. Postmenopausal women with osteoporosis at high risk for fracture, defined as:

   • History of osteoporotic fracture, OR
   • Multiple risk factors for fracture, OR
   • Patients who have failed or are intolerant to other available osteoporosis therapy

2. Men with osteoporosis at high risk for fracture (same criteria as above)

Clinical Efficacy

Fracture Risk Reduction

• In the pivotal ACTIVE trial, abaloparatide reduced vertebral fractures by 87% compared to placebo (risk ratio 0.13) 4
• Reduced nonvertebral fractures, clinical fractures, and major osteoporotic fractures compared to placebo 3
• When followed by sequential alendronate therapy, fracture protection is sustained through 42 months 3

Bone Density Improvements

• Increases lumbar spine bone mineral density by approximately 8.5% at 12 months 5
• Increases total hip BMD by approximately 2.1% at 12 months 5
• Increases femoral neck BMD by approximately 3.0% at 12 months 5
• These gains are significantly greater than placebo across all skeletal sites 4

Administration and Dosing

• Dose: 80 mcg administered subcutaneously once daily 1
• Site: Inject into the periumbilical region of the abdomen, rotating injection sites daily 1
• Timing: Administer at approximately the same time each day 1
• Duration: Maximum 2 years of treatment during a patient's lifetime; safety and efficacy beyond 2 years have not been established 1
• Supplementation: All patients must receive supplemental calcium and vitamin D if dietary intake is inadequate 1

Position in Treatment Algorithm

Based on current American College of Physicians guidelines, abaloparatide occupies a specific niche 6:

• NOT first-line therapy: Bisphosphonates remain the recommended initial treatment for osteoporosis due to superior cost-effectiveness and extensive safety data 6
• Reserved for very high-risk patients: The ACP conditionally recommends anabolic agents like abaloparatide (along with teriparatide and romosozumab) for females with primary osteoporosis at very high risk of fracture 6
• Second-line consideration: Appropriate for patients who have failed or are intolerant to bisphosphonates 1

Safety Profile and Adverse Events

Common Side Effects (≥5%)

The most frequently reported adverse events include 5:

• Injection site reactions
• Dizziness (particularly with initial doses)
• Nasopharyngitis
• Arthralgia
• Headache
• Palpitations and increased heart rate

Important Safety Considerations

• Orthostatic hypotension: Administer the first several doses where the patient can sit or lie down if necessary 1
• Hypercalcemia: Less frequent than with teriparatide, but monitoring is still warranted 7
• Discontinuation rates: Slightly higher than placebo due to dizziness, palpitations, nausea, and headache 3

Black Box Warning - Osteosarcoma Risk

• Critical warning: Abaloparatide caused dose-dependent osteosarcoma in male and female rats at exposures 4 to 28 times the human clinical dose 1
• It is unknown whether Tymlos will cause osteosarcoma in humans 1
• This is the same class warning that applies to teriparatide (another PTH-related anabolic agent) 1
• Due to this theoretical risk, lifetime use is limited to 2 years maximum 1

Contraindications

Tymlos is contraindicated in patients with 1:

• History of systemic hypersensitivity to abaloparatide or any component of the formulation
• Previous reactions including anaphylaxis, dyspnea, or urticaria

Sequential Therapy Strategy

• Optimal approach: Initiate abaloparatide for 18 months, then transition to alendronate for an additional 24 months to maintain and extend fracture protection 3
• This sequential strategy (anabolic followed by antiresorptive) maximizes bone density gains and sustains fracture risk reduction 3
• Do not use abaloparatide as maintenance therapy after bisphosphonates; anabolic agents should be used first when indicated 6

Comparison to Teriparatide

While both are anabolic agents, abaloparatide offers potential advantages 7:

• Lower incidence of hypercalcemia compared to teriparatide
• Reduced risk of major osteoporotic fractures compared to teriparatide in head-to-head comparison
• Lower cost than teriparatide, improving cost-effectiveness
• However, slightly higher occurrence of palpitations and increased heart rate compared to teriparatide 7

Product Formulation

• Supplied as a prefilled pen containing 3120 mcg/1.56 mL (2000 mcg/mL) 1
• Each pen delivers 30 doses of 80 mcg in 40 mcL 1
• Solution should be clear and colorless; do not use if cloudy, colored, or contains particles 1