This document addresses the use of abaloparatide (Tymlos™ ) injection manufactured by Radius Health, Inc. (Waltham, MA), which is a novel synthetic 34 amino acid peptide, intended for subcutaneous use. Abaloparatide is an analog of human parathyroid hormone related peptide, PTHrP (1-34) that selectively activates the parathyroid hormone type 1 receptor for the treatment of postmenopausal osteoporosis in a select population of women considered at high risk for fractures.
Note: Please see the following related document for additional information:
Abaloparatide (Tymlos) injection is considered medically necessary for the treatment of osteoporosis to increase bone mass when all the following criteria are met (A through F):
Not Medically Necessary:
Abaloparatide (Tymlos) injection is considered not medically necessary for any of the following (A, B, or C):
Note: Cumulative use of Tymlos and parathyroid hormone analogs (for example, teriparatide [Forteo]) for more than 2 years during an individual's lifetime is not recommended (FDA Black Box Warning, 2017).
Investigational and Not Medically Necessary:
Abaloparatide (Tymlos) injection is considered investigational and not medically necessary in males and when the criteria are not met and for all other indications.
On April 28, 2017 the U.S. Food and Drug Administration (FDA) approved abaloparatide (Tymlos) injection, which is indicated for the treatment of postmenopausal women with osteoporosis at high risk for fracture. This decision was based on the studies described below. Abaloparatide is intended for daily subcutaneous injection and is supplied in a pre-assembled disposable pen for self-injection use for up to 30 days. Notably, the FDA issued a Black Box Warning for risk of osteosarcoma as follows:
Additionally, Tymlos is not indicated for use in females of reproductive potential (FDA, 2017).
For additional warnings, precautions, and possible adverse reactions, see the FDA prescribing information.
To date, clinical trials of abaloparatide have consisted of a phase II dose ranging study (Leder, 2015) and one phase III double-blinded randomized controlled trial, the Abaloparatide Comparator Trial In Vertebral Endpoints (ACTIVE), which published results in 2016. From March 2011 to October 2014, 28 sites in 10 countries recruited postmenopausal women with bone mineral density (BMD) T-scores of less than or equal to -2.5 and greater than -5.0 at the lumbar spine or femoral neck, and radiological evidence of greater than or equal to 2 mild or 1 moderate lumbar or thoracic vertebral fracture or history of low-trauma nonvertebral fracture within the past 5 years. For 18 months, blinded, daily subcutaneous injections of placebo (n=821); abaloparatide, 80 μg (n=824); or open-label teriparatide, 20 μg (n=818) were administered. The primary endpoint was the percentage of participants with new vertebral fracture in the abaloparatide vs. placebo groups. Sample size was set to detect a 4% difference (57% risk reduction) between treatment groups. Secondary endpoints included change in BMD at total hip, femoral neck, and lumbar spine in abaloparatide-treated vs. placebo participants and time to first incident of nonvertebral fracture. Hypercalcemia was a prespecified safety endpoint in the abaloparatide-treated vs. teriparatide participants.
Results showed that, among 2463 women (mean age, 69 years [range, 49-86]), 1901 completed the study. New morphometric vertebral fractures occurred less frequently in the active treatment groups vs. placebo. The Kaplan-Meier estimated event rate for nonvertebral fracture was lower with abaloparatide vs. placebo. BMD increases were greater with abaloparatide than placebo (all p<0.001). The incidence of hypercalcemia was lower with the abaloparatide group (3.4%) vs. the teriparatide group (6.4%) (risk difference [RD], -2.96 [95% confidence interval (CI), -5.12 to -0.87]; p=0.006). The authors concluded that among postmenopausal women with osteoporosis, the use of subcutaneous abaloparatide, compared with placebo, reduced the risk of new vertebral and nonvertebral fractures over 18 months. However, further research is needed to understand the clinical importance of the difference in risk (RD), the risks and benefits of abaloparatide treatment, and the efficacy of abaloparatide vs. other osteoporosis treatment options (Miller, 2016).
According to the National Institute of Arthritis and Musculoskeletal and Skin Diseases (2014), more than 53 million people in the United States today either have osteoporosis or are at high risk for the disease, as a result of low bone mass. Osteoporosis is a disease in which the bones become weak and are more likely to break. The disease is 4 times more likely to occur in women than in men. It is estimated that a total of 1.5 million fractures occurring annually, (that is, 1 out of every 2 women over age 50) are due to osteoporosis. These fractures are most common at the hip, spine, and wrist and can result in serious morbidity, including death. As the U.S. population ages, the incidence of osteoporosis in the U.S. is expected to increase significantly in the future.
Abaloparatide most closely compares with Forteo (teriparatide), which is a recombinant human parathyroid hormone that stimulates bone formation. Abaloparatide is indicated for treatment of postmenopausal women with osteoporosis who are determined to be at higher-than-average risk for non-vertebral fractures. Both Forteo and abaloparatide are for daily subcutaneous injections. According to the American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) clinical practice guidelines for the diagnosis and treatment of postmenopausal osteoporosis (updated 2016), Forteo has a 2 year lifetime maximum limitation of use (Grade A, BEL: 1), due to the lack of long-term safety data, and an FDA Black Box warning for possible risk of osteosarcoma. The FDA labeling for abaloparatide (Tymlos) injection contains this same 2 year limitation of use due to possible risk for osteosarcoma.
Osteopenia: A condition of bone in which decreased calcification, decreased density, or reduced mass occurs (defined as a BMD T-score between -1.0 and -2.5 SD).
Osteoporosis: Loss of normal bone density, mass and strength, leading to increased porousness and vulnerability to fracture (defined as a BMD T-score of -2.5 or less).
Refractory (to treatment for osteoporosis): This term refers to ineffectual clinical results of medical therapy which, regarding osteoporosis, results in conditions, such as continued loss of bone mass or occurrence of low-trauma fractures, despite compliance with prescribed treatment doses of medications, such as oral bisphosphonates.
The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.
When services may be Medically Necessary when criteria are met:
|J3490||Unclassified drugs [when specified as abaloparatide (Tymlos)]|
|M80.00XA-M80.88XS||Osteoporosis with current pathological fracture|
|M81.0-M81.8||Osteoporosis without current pathological fracture|
When services are Not Medically Necessary:
For the procedure and diagnosis codes listed above in the situations indicated in the Position Statement section as not medically necessary.
When services are Investigational and Not Medically Necessary:
For the procedure and diagnosis codes listed above when criteria are not met or for all other diagnoses not listed; or when the code describes a procedure indicated in the Position Statement section as investigational and not medically necessary.
Peer Reviewed Publications:
Government Agency, Medical Society, and Other Authoritative Publications:
|Websites for Additional Information|
The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.
|Revised||08/03/2017||Medical Policy & Technology Assessment Committee (MPTAC) review. The medically necessary criteria were revised to remove raloxifene and calcitonin nasal spray and to add: The individual has sustained an osteoporotic low trauma fracture (fragility fracture) while on an oral bisphosphonate to Criterion C and to add a new Criterion D for: The individual has been refractory to, or intolerant of, or has a contraindication to Forteo (teriparatide). Updated References section.|
|Reviewed||05/15/2017||MPTAC interim review and approval.|
|New||05/04/2017||MPTAC review. Initial document development.|
|Preliminary discussion||02/02/2017||MPTAC review. Pre-FDA approval review.|