What is the current black box warning on Tymlos (abaloparatide)?

From the Guidelines

Tymlos (abaloparatide) carries a black box warning for potential increased risk of osteosarcoma, a type of bone cancer, and should not be prescribed to patients at increased risk for osteosarcoma. The warning is based on animal studies where rats developed osteosarcoma at doses that produced systemic exposures to abaloparatide ranging from 4 to 28 times the exposure in humans at the recommended human dose, similar to the concerns with teriparatide [parathyroid hormone (1–34)] which also has a black box warning against its use in children due to risk of osteosarcoma 1. Key points to consider when prescribing Tymlos include:

• Patients with Paget's disease of bone, unexplained elevations of alkaline phosphatase, open epiphyses, prior external beam or implant radiation therapy involving the skeleton, or patients with a history of skeletal malignancies are at increased risk
• The lifetime cumulative use of Tymlos and other parathyroid hormone analogs (like teriparatide) should not exceed 2 years
• Patients should be informed of the potential risks and benefits of Tymlos, and the medication should only be prescribed to patients for whom the potential benefits outweigh the potential risk. It is essential to carefully evaluate the risk-benefit ratio for each patient before initiating Tymlos therapy, considering the potential for increased risk of osteosarcoma.

From the FDA Drug Label

5 WARNINGS AND PRECAUTIONS

5.1 Risk of Osteosarcoma 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 [see Nonclinical Toxicology (13. 1)]. It is unknown whether TYMLOS will cause osteosarcoma in humans. Osteosarcoma has been reported in patients treated with a PTH-analog in the post marketing setting; however, an increased risk of osteosarcoma has not been observed in observational studies in humans There are limited data assessing the risk of osteosarcoma beyond 2 years of TYMLOS and/or use of a PTH-analog [see Dosage and Administration (2.3) and Nonclinical Toxicology (13. 1)]. Avoid TYMLOS use in patients with (these patients are at increased baseline risk of osteosarcoma): Open epiphyses (pediatric and young adult patients) (TYMLOS is not approved in pediatric patients) [see Use in Specific Populations (8. 4)]. Metabolic bone diseases other than osteoporosis, including Paget's disease of the bone. Bone metastases or a history of skeletal malignancies. Prior external beam or implant radiation therapy involving the skeleton. Hereditary disorders predisposing to osteosarcoma.

The current black box warning on Tymlos (abaloparatide) is for the Risk of Osteosarcoma. The warning states that abaloparatide caused an increase in the incidence of osteosarcoma in rats, and it is unknown whether Tymlos will cause osteosarcoma in humans. The warning advises to avoid Tymlos use in patients with certain conditions that increase the baseline risk of osteosarcoma, including:

• Open epiphyses (pediatric and young adult patients)
• Metabolic bone diseases other than osteoporosis
• Bone metastases or a history of skeletal malignancies
• Prior external beam or implant radiation therapy involving the skeleton
• Hereditary disorders predisposing to osteosarcoma 2

From the Research

Black Box Warning on Tymlos (Abaloparatide)

• The current black box warning on Tymlos (abaloparatide) is not explicitly stated in the provided studies 3, 4, 5, 6, 7.
• However, it is worth noting that abaloparatide is an osteoanabolic agent, and as such, it may carry similar warnings to other drugs in its class.
• A black box warning is typically reserved for serious or life-threatening side effects, and it is possible that Tymlos may carry a warning related to its potential to cause osteosarcoma, a rare but serious bone cancer 3.
• Additionally, abaloparatide may carry a warning related to its potential to cause increased heart rate or palpitations, as noted in the study by 4.
• It is also possible that Tymlos may carry a warning related to its potential to cause other serious side effects, such as hypercalcemia or increased risk of cardiovascular events, although these are not explicitly stated in the provided studies.

Comparison to Other Osteoporosis Treatments

• Abaloparatide has been shown to be effective in reducing the risk of vertebral, nonvertebral, major osteoporotic, and clinical fractures in postmenopausal women with osteoporosis 4, 7.
• Compared to other osteoporosis treatments, such as teriparatide and denosumab, abaloparatide has been shown to have a similar or improved safety profile 4, 5.
• However, the choice of osteoporosis treatment ultimately depends on individual patient factors, such as medical history, lifestyle, and personal preferences.

Osteosarcoma Risk

• The risk of osteosarcoma associated with abaloparatide is not well established, although it is a potential concern based on animal studies 3.
• A study by 3 found no cases of osteosarcoma in patients treated with teriparatide, a similar osteoanabolic agent, although the study had limitations and the follow-up period was relatively short.
• Further studies are needed to fully understand the risk of osteosarcoma associated with abaloparatide and other osteoanabolic agents.