Evenity From Amgen

Pharmacy Times, July 2019 Gastrointestinal Issues, Volume 85, Issue 7

Amgen is indicated to treat osteoporosis in postmenopausal women at high risk for fracture.

The FDA has approved evenity (romosozumab-aqqg), from Amgen, to treat osteoporosis in postmenopausal women at high risk for fracture. The approval carries the limitation that no more than 12 once-monthly doses should be administered. If osteoporosis treatment is still needed after all 12 doses have been given, treatment with an antiresorptive agent should be considered.1

PHARMACOLOGY AND PHARMACOKINETICS

Evenity is a humanized immunoglobulin G2 monoclonal antibody that inhibits sclerostin to increase osteoblastic activity. This leads to new bone formation and, to a lesser extent, decreased bone resorption.1,2 Evenity displays nonlinear pharmacokinetics. It reaches maximum plasma concentrations 5 days after subcutaneous administration and displays a mean effective elimination half-life of 12.8 days.1

DOSAGE AND ADMINISTRATION

Evenity is supplied as a 105-mg solution in a single-use, prefilled syringe; 2 separate subcutaneous injections, given 1 after the other, are required to administer the total dose of 210 mg once every month for 12 doses. It should be administered by a health care provider in the abdomen, the thigh, or the upper arm. Patients using Evenity should receive adequate calcium and vitamin D supplementation.1

CLINICAL TRIALS

The FDA approval of Evenity was based on 2 double-blind, randomized phase 3 clinical trials. In addition to daily calcium and vitamin D supplementation, participants in the first trial received subcutaneous injections of either Evenity or placebo for 12 months. Both groups then transitioned to open-label antiresorptive therapy for a year while remaining blinded to their initial treatment. The study found that treatment with Evenity significantly reduced the incidence of new vertebral fractures at 12 months compared with the placebo, and this reduction in fracture risk continued through the second year. Additionally, the Evenity group demonstrated a significant increase in bone mineral density (BMD) at the femoral neck, the lumbar spine, and the total hip at 12 months, and BMD continued to increase through 24 months.

Participants in the second trial received either monthly subcutaneous injections of Evenity or oral alendronate 70 mg weekly for 12 months, with daily calcium and vitamin D supplementation. After 12 months, all participants transitioned to open-label alendronate 70 mg weekly while remaining blinded to their initial treatment. Patients using Evenity had a significant reduction in new vertebral fracture at 24 months and a significantly reduced risk of clinical fracture at 33 months. The Evenity group also demonstrated a significant increase in BMD at the femoral neck, the lumbar spine, and the total hip at 12 months. Evenity followed by alendronate was found to significantly increase BMD more than alendronate alone.1,2

CONTRAINDICATIONS, WARNINGS, AND PRECAUTIONS

Evenity carries a boxed warning that the medication may increase the risk of cardiovascular death, myocardial infarction (MI), and stroke and that it should not be used in patients who have had an MI or a stroke within the previous year. Patients with other cardiovascular risk factors should be evaluated to determine whether the benefits of treatment outweigh the risks. Evenity should be discontinued if an MI or a stroke occurs during treatment.

The use of Evenity is contraindicated in patients with hypocalcemia or a history of systemic hypersensitivity to any of its components. Patients using Evenity should be monitored for MI and stroke and obtain prompt medical attention if symptoms of either occur. Hypersensitivity reactions, such as angioedema, dermatitis, erythema multiforme, rash, and urticaria have occurred during treatment with Evenity. The medication should be discontinued if an anaphylactic or other clinically significant allergic reaction occurs. Hypocalcemia has occurred in patients using Evenity. Patients taking Evenity should be monitored for osteonecrosis of the jaw. New or unusual groin, hip, or thigh pain should be evaluated to rule out an incomplete femur fracture. Patients with severe renal impairment or who are receiving dialysis are at greater risk of developing hypocalcemia during treatment with Evenity, and these patients should have their serum calcium monitored and receive supplementation with calcium and vitamin D.

The most common adverse reactions (≥5% incidence) were arthralgia and headache.1

Monica Holmberg, PharmD, BCPS, earned her PharmD at the University of Connecticut in Storrs and completed an ambulatory care residency at the Phoenix VA Health Care System in Arizona. Her practice has also included pediatrics and inpatient mental health. She lives in Phoenix.

References

  • Evenity [prescribing information]. Thousand Oaks, CA: Amgen Inc; 2019. pi.amgen.com/~/media/amgen/repositorysites/pi-amgen-com/evenity/evenity_pi_hcp_english.ashx. Accessed April 23, 2019.
  • FDA approves Evenity (romosozumab-aqqg) for the treatment of osteoporosis in postmenopausal women at high risk for fracture [news release]. Thousand Oaks, CA, and Brussels, Belgium: Amgen Inc and UCB; April 9, 2019. amgen.com/media/news-releases/2019/04/fda-approves-evenity-romosozumabaqqg-for-the-treatment-of-osteoporosis-in-postmenopausal-women-at-high-risk-for-fracture/. Accessed April 23, 2019.