Tymlos is a unique form of parathyroid hormone therapy for osteoporosis. It is called PTHrp and we think it its physiologic role is primarily in the life of very young even fetal life during rapid bone growth and modeling. It increases bone formation without first increasing bones reabsorption. In the young, bone removal is needed only to the extent that it needs to be modeled not because it is effete and must been replaced. This feature of Tymlos results in outsized increases in bone mass and density with its use compared with Forteo when it was used together in an open label comparator study. This differential effect over Forteo was most apparent in the hip’s femoral neck DXA measurement site.
Indications and Usage for Tymlos from the Label
TYMLOS is indicated for the treatment of postmenopausal women 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. In postmenopausal women with osteoporosis, TYMLOS reduces the risk of vertebral fractures and nonvertebral fractures.
Efficacy Study in Women with Postmenopausal Osteoporosis
Treatment of postmenopausal osteoporosis was evaluated in an 18-month, study of 1645 postmenopausal women with osteoporosis whose average age were 69, and 80% were white. 24% had vertebral fractures at the beginning of the study. All subjects received calcium and vitamin D for the 18 month study duration.
The new vertebral fracture rate in the placebo treated subjects was 42 in 1,000 vs. 6 in 1,000 fractures in the Tymlos group representing a 86% statistically significant relative risk reduction and a 3.6% absolute risk reduction. To prevent 1 new vertebral fracture in women like those in the study would require treatment of 28 women for 28 days.
The study was too small to look a hip fracture risk.
In the peripheral skeleton that included the hip and wrist the in the placebo group relative risk reduction was 43% with a fracture rate of 47 per 1,000 vs. 27 per 1,000 on the Tymlos subjects. The absolute risk reduction was a statistically significant 2%. To prevent 1 peripheral fracture requires treating 50 women like those in the study for 18 months.
Bone density increased 9.2% in the spine, 3.4% in the total hip and 2.7 in the femoral neck.
Limitations of Use
Because of the unknown relevance of the rodent osteosarcoma findings to humans, cumulative use of TYMLOS and parathyroid hormone analogs (e.g., teriparatide) for more than 2 years during a patient’s lifetime is not recommended
- Orthostatic Hypotension low blood pressure can occur within 4 hours of the injection. Associated symptoms may include dizziness, palpitations, tachycardia, or nausea. Lying down helps. Taking the medication before bed helps.
- Hypercalcemia TYMLOS naturally raises the serum calcium. This is expected to happen and is not a concern. Drink plenty of water when using Tymlos.
- Hypercalciuria and Urolithiasis TYMLOS causes increased calcium in the urine and could cause kidney stones in some people. Drink plenty of water when taking Tymlos as this helps dilute the calcium in the urine and prevent kidney stones. This is a rare side effect.
Warnings and Precautions
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. It is unknown whether TYMLOS will cause osteosarcoma in humans. The use of TYMLOS is not recommended in patients at increased risk of osteosarcoma including those with Paget’s disease of bone or unexplained elevations of alkaline phosphatase, open epiphyses, bone metastases or skeletal malignancies, hereditary disorders predisposing to osteosarcoma, or prior external beam or implant radiation therapy involving the skeleton. Cumulative use of TYMLOS and parathyroid hormone analogs (e.g., teriparatide) for more than 2 years during a patient’s lifetime is not recommended.
This warning has become standard boilerplate now for this and all PTH-like drugs. So far, they have all triggered osteogenic sarcoma in the Fisher 344 rat that is used by the pharmaceutical companies at the direction of the US FDA to test these agents. The fact that over 1,000,000 people worldwide have been treated with 1-34 Teraparatide, a PTH similar to Tymlos and none of these people have experienced osteogenic sarcoma is really interesting. There should have been 50 cases of this rare fatal cancer by chance alone since that drug first came on the market in 2002. So far, there have been no cases. Certainly, the US FDA is aware of this fact. Why do they insist that this warning be placed on this new drug and continue on the Teraparatide label when it is clear that these legitimate fears surrounding this drug when it was first introduced have not manifest?