What is Abaloparatide?
Abaloparatide (brand name TYMLOS, also marketed as ELADYNOS in the EU; development code BA058) is a synthetic 34-amino-acid analogue of parathyroid hormone-related protein (PTHrP 1-34). It was approved by the FDA on April 28, 2017 as an anabolic (bone-building) therapy for postmenopausal osteoporosis, expanded in 2022 to include men with osteoporosis.
Like teriparatide, abaloparatide is administered as a once-daily subcutaneous injection and acts at the PTH1 receptor. Unlike teriparatide (which is recombinant native PTH 1-34), abaloparatide is a synthetic peptide based on the PTHrP backbone with several modifications to favor a specific receptor conformation.
Mechanism of Action
The PTH1 receptor exists in equilibrium between two conformations:
- R0 conformation — high-affinity, prolonged signaling, stronger bone resorption
- RG conformation — lower-affinity, transient signaling, stronger bone formation
Teriparatide binds both R0 and RG with similar affinity. Abaloparatide is biased toward the RG conformation, producing a more transient receptor activation with proportionally greater anabolic-to-resorptive effect.
In practice this translates to:
- Comparable or larger spine and total hip BMD gains vs teriparatide
- Less stimulation of bone resorption markers
- Smaller hypercalcemia signal during dose titration
Clinical Evidence
ACTIVE Phase 3 (JAMA 2016):
- 2,463 postmenopausal women with osteoporosis randomized to abaloparatide, teriparatide, or placebo for 18 months
- New vertebral fractures: 0.6% abaloparatide vs 4.2% placebo (86% reduction)
- Non-vertebral fractures: HR 0.57 vs placebo (significant)
- Lumbar spine BMD gain numerically greater than teriparatide; hip BMD gain significantly greater than teriparatide
ACTIVExtend (Mayo Clin Proc 2017):
- 18 months of abaloparatide followed by alendronate (sequential anabolic-then-antiresorptive therapy)
- Sustained fracture-risk reduction through 43 months total
Approval History
- April 28, 2017 — FDA approval for postmenopausal women with osteoporosis at high fracture risk
- December 2022 — FDA expanded to include men with osteoporosis at high fracture risk
- EMA approved — December 2022 (after initial 2018 rejection on benefit-risk grounds; resubmission with additional data succeeded)
Place in Therapy
Abaloparatide is positioned alongside teriparatide as an anabolic option for severe osteoporosis. Choice between them depends on:
- Hip BMD priority — abaloparatide may produce larger hip gains
- Hypercalcemia risk — abaloparatide tends to produce less hypercalcemia
- Cost and access — varies by formulary
The treatment course is typically 18-24 months, followed by an antiresorptive agent to consolidate gains (similar to teriparatide). The earlier 24-month lifetime limit was based on rat carcinogenicity precedent and was removed from the US label in 2022.
Distinction from Teriparatide and Palopegteriparatide
Three PTH-axis peptide drugs in the same family:
| Drug | Peptide source | Receptor bias | Indication |
|---|---|---|---|
| Teriparatide (Forteo) | Native PTH 1-34 | R0/RG balanced | Anabolic — osteoporosis |
| Abaloparatide (Tymlos) | Synthetic PTHrP analogue | RG-biased | Anabolic — osteoporosis |
| Palopegteriparatide (Yorvipath) | Teriparatide prodrug | (continuous release) | Replacement — hypoparathyroidism |
Safety Profile
The most common adverse events are hypercalcemia, dizziness, nausea, headache, palpitations, and arthralgia. Orthostatic hypotension after the first dose is similar to teriparatide. The prior boxed warning for osteosarcoma based on rat data was removed in 2022 after long-term human observational data showed no increased osteosarcoma risk.