Tymlos (abaloparatide) Policy Number: 5.01.638 Last Review: 11/2018 Origination: 10/2017 Next Review: 11/2019 Policy Blue Cross and Blue Shield of Kansas City (Blue KC) will provide coverage for Tymlos when it is determined to be medically necessary because the following criteria have been met. When Policy Topic is covered Abaloparatide (Tymlos) injection is considered medically necessary for the treatment of osteoporosis to increase bone mass when all the following criteria are met: 1. Osteoporosis Treatment for a Postmenopausal Patient. Approve Tymlos for 1 year if the patient meets the following criteria (A and B): A) The patient meets ONE of the following conditions (i, ii, or iii): i. The patient has had a T-score (current or at any time in the past) at or below -2.5 at the lumbar spine, femoral neck, total hip and/or 33% (one-third) radius (wrist); OR ii. The patient has had an osteoporotic fracture or a fragility fracture; OR iii. The patient has low bone mass (T-score [current or at any time in the past] between -1.0 and -2.5 at the lumbar spine, femoral neck, total hip and/or 33% [one-third] radius [wrist]) and the physician determines the patient is at high risk for fracture; AND B) The patient meets ONE of the following (i, ii, iii, or iv): i. The patient has tried one oral bisphosphonate or oral bisphosphonate-containing product and meets one of the following (a, b, or c): a) The patient has had an inadequate response to oral bisphosphonate therapy after a trial duration of 12 months as determined by the prescribing physician (e.g., ongoing and significant loss of BMD, lack of BMD increase); OR b) The patient has had an osteoporotic fracture or fragility fracture while receiving oral bisphosphonate therapy; OR c) The patient has experienced intolerability to an oral bisphosphonate (e.g., severe gastrointestinal [GI]-related adverse effects, severe musculoskeletal-related side effects, a femoral fracture); OR ii. The patient cannot take an oral bisphosphonate due to one of the following circumstances (a, b, or c): a) The patient cannot swallow or has difficulty swallowing; OR b) The patient cannot remain in an upright position post oral bisphosphonate administration; OR c) The patient has a pre-existing gastrointestinal (GI) medical condition (e.g., patient with esophageal lesions, esophageal ulcers, or abnormalities of the esophagus that delay esophageal emptying [stricture, achalasia]); OR iii. The patient has tried ibandronate injection (Boniva) or zoledronic acid injection (Reclast); OR iv. The patient meets one of the following conditions (a, b, or c): a) Severe renal impairment (creatinine clearance < 35 ml/min); OR b) Chronic kidney disease (CKD); OR c) The patient has had an osteoporotic fracture or a fragility fracture.
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. 1 Guidelines support use of bisphosphonate therapy as first-line in many clinical scenarios. 4-6 In the AACE guidelines for PMO, osteoporosis is defined as a T-score of -2.5 or below in the lumbar spine, femoral neck or total hip and/or 33% (one-third) radius (wrist). Other scenarios also are indicators for a diagnosis of osteoporosis (e.g., low-trauma spine or hip fracture [regardless of BMD]). 4 Bisphosphonates should not be used in patients with renal impairment. Oral bisphosphonates have caused severe gastrointestinal (GI) AEs and severe musculoskeletal pain has been reported. Oral bisphosphonates are contraindicated if patients have abnormalities of the esophagus which delay emptying (stricture or achalasia). When Policy Topic is not covered Abaloparatide (Tymlos) injection is considered investigational for any of the following: Tymlos has not been shown to be effective, or there are limited or preliminary data or potential safety concerns that are not supportive of general approval for the following conditions. (Note: This is not an exhaustive list of Conditions Not Recommended for Approval.) 1. Osteoporosis Prevention. Tymlos has not been studied in this patient population. The benefits and risks of building bone with Tymlos in a condition in which substantial bone loss has not occurred have not been investigated. 1 2. Previous Use of Tymlos and/or Forteo For A Combined Total No Greater Than 2 Years Duration During a Patient s Lifetime. The prescribing information for Tymlos states that cumulative use of Tymlos and parathyroid hormone analogs (e.g., Forteo [teraparatide injection for SC use) collectively for > 2 years during a patient s lifetime is not recommended. This is related to the risk of osteosarcoma. 1,7-8 3. Concurrent Use of Tymlos with Other Medications for Osteoporosis (e.g., Prolia, bisphosphonates [alendronate, risedronate, ibandronate, zoledronic acid injection {Reclast}], calcitonin nasal spray, Forteo), except calcium and Vitamin D. 4. Coverage is not recommended for circumstances not listed in the Recommended Authorization Criteria. Criteria will be updated as new published data are available. Considerations Tymlos requires prior authorization through the Clinical Pharmacy Department. This Blue Cross and Blue Shield of Kansas City policy Statement was developed using available resources such as, but not limited to: Food and Drug Administration (FDA) approvals, Facts and Comparisons, National specialty guidelines, Local medical policies of other health plans, Medicare (CMS), Local providers. Description of Procedure or Service 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 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. 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. Rationale 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: 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. 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). References Peer Reviewed Publications: 1. Crandall CJ, Newberry SJ, Diamant A, et al. Comparative effectiveness of pharmacologic treatments to prevent fractures: an updated systemic review. Ann Internal Med. 2014; 161(10):711-723. 2. Ev M, H J, A O, et al. The effect of abaloparatide-sc on fracture risk is independent of baseline FRAX fracture probability: A post hoc analysis of the ACTIVE study. J Bone Miner Res. 2017 May 5 [Epub ahead of print]. 3. Leder BZ, ODea SL, Zanchetta JR, et al. Effects of abaloparatide, a human parathyroid hormone-related peptide analog, on bone mineral density in postmenopausal women with osteoporosis. J Clin Endocrinol Metab. 2015; 100(2):697-706. 4. Miller PD, Hattersley G, Riis BJ, et al. Effect of abaloparatide vs placebo on new vertebral fractures in postmenopausal women with osteoporosis. JAMA. 2016; 316(7):722-733. 5. Silverman S, Christiansen C. Individualizing osteoporosis therapy. Osteoporos Int. 2012; 23(3):797-809. Government Agency, Medical Society, and Other Authoritative Publications: 1. Abaloparatide (Tymlos) injection Monograph. Lexicomp Online, American Hospital Formulary Service (AHFS ) Online, Hudson, Ohio, Lexi-Comp., Inc. Last revised April 2017. Accessed on May 9, 2017. 2. Abaloparatide (Tymlos) injection. In: DrugPoints System (electronic version). Truven Health Analytics, Greenwood Village, CO. Updated April 2017. Available at: http://www.micromedexsolutions.com/micromedex2/librarian/pfdefaultactionid/evidencexpe rt.dointegratedsearch#. Accessed on May 9, 2017. 3. Agency for Healthcare Research and Quality. Treatment to prevent fractures in men and women with low bone density or osteoporosis: update of a 2007 Report. Comparative effectiveness review. 2012 March. Publication No 12-EHC023-EF. Available at: http://www.ncbi.nlm.nih.gov/books/nbk92566/pdf/toc.pdf. 4. American Association of Clinical Endocrinologists and American College of Endocrinology. Clinical practice guidelines for the diagnosis and treatment of postmenopausal osteoporosis. Endocr Pract. 2016; 22(Suppl 4):1-42. Available at: https://www.aace.com/files/postmenopausal-guidelines.pdf. 5. Camacho PM, Petak SM, Binkley N, et al. American Association of Clinical Endocrinologists/American College of Endocrinology (AACE/ACE) clinical practice guidelines for the diagnosis and treatment of postmenopausal osteoporosis. 2016. Endocr Prac. 2016; 22(Suppl 4).
6. Cosman F, de Beur SJ, LeBoff MS, et al. Clinician's guide to prevention and treatment of osteoporosis. Osteoporosis Int. 2014. Available at: https://www.ncbi.nlm.nih.gov/pubmed/25182228. 7. Grossman JM, Gordon R, Ranganath VK, et al. American College of Rheumatology 2010 Recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis. Revised 2010. Available at: http://www.rheumatology.org/practice/clinical/guidelines/clinical_practice_guidelines/. 8. National Institute of Health (NIH). Osteoporosis and related bone diseases. National resource center. June 2015. Available at: https://www.niams.nih.gov/health_info/bone/bone_health/bone_mass_measure.asp. 9. National Institute of Health (NIH). Osteoporosis prevention, diagnosis, and therapy. NIH Consensus Statement. 2000; 17(1):1-45. Available at: http://consensus.nih.gov/2000/2000osteoporosis111html.htm. 10. National Osteoporosis Foundation. Clinician's guide to prevention and treatment of osteoporosis. Revised 2013. Available at: https://my.nof.org/bone-soruce/education/cliniciansguide-to-the-prevention-and-treatment-of-osteoporosis. 11. North American Menopause Society. Management of osteoporosis in postmenopausal women: 2010 position statement of the North American Menopause Society. Menopause. 2010; 17(1):25-54. 12. Qaseem A, Forciea MJ, McClean RM, et al. American College of Physicians (ACP). Treatment of low bone density or osteoporosis to prevent fractures in men and women: A clinical practice guideline update from the American College of Physicians. Ann Int Med. 2017 May [Epub ahead of print]. 13. U.S. Food and Drug Administration (FDA). TYMLOS (abaloparatide) injection [Prescribing Information]. Radius Health, Inc. Waltham WA. April 2017. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208743lbl.pdf. Accessed on May 9, 2017. 14. Watts NB, Bilezikian JP, Camacho PM, et al. American Association of Clinical Endocrinologists (AACE). Medical guidelines for clinical practice for the diagnosis and treatment of postmenopausal osteoporosis. Endocr Pract. 2010; 16(Suppl 3):1-37. Websites for Additional Information 1. International Osteoporosis Foundation. The global burden of osteoporosis. What you need to know. Available at: https://www.iofbonehealth.org/data-publications/fact-sheets/what-you-needknow-about-osteoporosis. 2. International Osteoporosis Foundation. Who's at risk? 2015. Available at: https://www.iofbonehealth.org/whos-risk. 3. National Institute of Arthritis and Musculoskeletal and Skin Diseases. Osteoporosis handout on health. August 2014. Available at: http://www.niams.nih.gov/health_info/osteoporosis/default.asp. 4. National Institute of Health. Osteoporosis and Related Bone Diseases National Resource Center. What is Osteoporosis? Updated November 2014. Available at: http://www.niams.nih.gov/health_info/bone/osteoporosis/osteoporosis_ff.asp. Accessed on May 1, 2017.
Billing Coding/Physician Documentation Information Tymlos is considered a specialty pharmacy benefit Additional Policy Key Words 5.01.638 Policy Implementation/Update Information 10/2017 New policy titled Tymlos (abaloparatide) 10/2018 Policy reformatted no changes made to coverage statement State and Federal mandates and health plan contract language, including specific provisions/exclusions, take precedence over Medical Policy and must be considered first in determining eligibility for coverage. The medical policies contained herein are for informational purposes. The medical policies do not constitute medical advice or medical care. Treating health care providers are independent contractors and are neither employees nor agents Blue KC and are solely responsible for diagnosis, treatment and medical advice. No part of this publication may be reproduced, stored in a retrieval system or transmitted, in any form or by any means, electronic, photocopying, or otherwise, without permission from Blue KC.