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FDA approves romosozumab (Evenity®) for the treatment of postmenopausal osteoporosis

By: Michael Lim, PharmD Candidate c/o 2020

           Osteoporosis is a bone disease affecting nearly ten million people in the United States.1 It can be caused by excess bone loss, insufficient bone production, or a combination of both factors. The disease is responsible for two million broken bones and 19 billion dollars in related healthcare costs annually.2 Osteoporosis is often treated with the bisphosphonate class of medications. As first-line therapy for osteoporosis, the bisphosphonates stop the loss of bone by inhibiting bone resorption by osteoclasts.3 On the other hand, alternative treatments such as parathyroid hormone build and break down bone.4 In April 2019, a new treatment strategy was introduced to the market with the Food and Drug Administration’s (FDA) approval of romosozumab (Evenity®).

Romosozumab is a humanized monoclonal antibody approved for the treatment of osteoporosis in postmenopausal women with a high risk of fracture.4 The drug differs from other osteoporosis treatments in that it restores bone without breaking it down. Romosozumab functions by blocking the actions of the sclerostin protein, a regulatory factor in bone metabolism, and by increasing new bone formation.5 The new treatment strategy found its origin in a rare genetic mutation in individuals with bones so dense that they never break. These individuals, which were an unusual group of Afrikaner patients from South Africa, developed bones that grew profusely, leading to overgrown skulls and jaws. Scientists studying the patients discovered that their large dense bones were the result of a mutation that stopped the production of sclerostin. As a result, their bodies would continuously produce bone. To mimic the effects of this mutation, researchers developed the romosozumab antibody which allows osteoporosis patients to build more bone.4

Romosozumab has a black box warning for increasing the risk of myocardial infarction, stroke, and cardiovascular death.5 Consequently, the drug should not be initiated in patients who have had a myocardial infarction or stroke within the preceding year. Furthermore, the occurrence of a myocardial infarction or stroke during therapy merits discontinuation.5 Romosozumab is contraindicated in patients with hypocalcemia and patients taking the drug are advised to supplement with calcium and vitamin D during therapy. In patients with severe renal impairment or those who are receiving dialysis, a greater risk of hypocalcemia exists and serum calcium monitoring is recommended.5

Common adverse effects of romosozumab include joint pain and headache.5 The subcutaneous injections may also cause irritation at the injection site. Romosozumab must be refrigerated in its original carton and protected from light.5 However, if removed from the refrigerator it may be kept at room temperature up to 25oC (77oF) in the original carton for use within 30 days.

When tested in clinical trials, patients taking romosozumab experienced increases in spinal bone density in the range of fifteen percent.4 According to Dr. Clifford J. Rosen, MD, an osteoporosis expert at Maine Medical Center Research Institute and a member of the FDA panel that evaluated the drug’s clinical trial data, such increases are akin to the amount of bone made during early adolescence.4 Two clinical trials involving more than 11,000 women with postmenopausal osteoporosis demonstrated the safety and efficacy of romosozumab.1 In one trial, a year of treatment with romosozumab decreased the risk of a new vertebral fracture by 73 percent compared to placebo. During the second year of the trial, the benefit was maintained when romosozumab was followed by one year of denosumab treatment compared to placebo followed by denosumab.1 In another clinical trial, one year of treatment with romosozumab followed by one year of treatment with alendronate decreased the risk of a new vertebral fracture by 50 percent as well as the risk of nonvertebral fractures compared to two years of alendronate treatment alone.1

A single dose of the drug consists of two subcutaneous injections given monthly.5 The injections are available as single-use prefilled syringes and can be administered in the abdomen, thigh, or upper arm.5 The two separate injections follow one another to deliver a total dose of 210 mg. However, the bone forming effect of romosozumab diminishes after twelve doses, therefore, no more than twelve doses should be administered.5 When twelve doses have been administered, an alternative osteoporosis treatment should be used to continue therapy, allowing the patient to maintain their newly formed bone.

From a pharmacist’s perspective, patients taking romosozumab can be counseled to ensure its safe and efficacious use. For example, pharmacists can advise patients to seek immediate medical attention if they experience symptoms such as urticaria or angioedema. Furthermore given the drug’s warning for increased risk of cardiac events, pharmacists can counsel patients to self-monitor for signs and symptoms of heart attack or stroke. Pharmacists can also remind patients taking romosozumab of the importance of calcium and vitamin D supplementation to prevent hypocalcemia.

Romosozumab may be a useful second-line option in osteoporotic therapy. While it cannot be used indefinitely, its novel mechanism of action offers a new and unique approach to the disease state. Moving forward, it will be interesting to see how romosozumab changes the management of osteoporosis and whether it plays a more significant role in therapy in the future.

SOURCES:

  1. Food and Drug Administration. FDA approves new treatment for osteoporosis in postmenopausal women at high risk of fracture. U.S. Food and Drug Administration. https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-osteoporosis-postmenopausal-women-high-risk-fracture. Published 04/09/19. Accessed 10/01/19.
  2. National Osteoporosis Foundation. What is Osteoporosis and What Causes It? National Osteoporosis Foundation. https://www.nof.org/patients/what-is-osteoporosis/. Published 2019. Accessed 10/01/19.
  3. Rosen HN. Pharmacology of bisphosphonates. UpToDate. https://www-uptodate-com.jerome.stjohns.edu/contents/pharmacology-of-bisphosphonates?search=bisphosphonates&source=search_result&selectedTitle=2~150&usage_type=default&display_rank=2. Published 04/08/19. Accessed 10/01/19.
  4. Kolata G. Most Osteoporosis Drugs Don’t Build Bone. This One Does. The New York Times. https://www.nytimes.com/2019/04/09/health/osteoporosis-evenity-bone-amgen.html. Published 04/09/19. Accessed 10/01/19.
  5. Evenity (Romosozumab-aqqg) [package insert]. Thousand Oaks, CA; Amgen Inc.; Revised 04/01/2019.

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