Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion recommending Marketing Authorization for EVENITY® (romosozumab) for the treatment of severe osteoporosis in postmenopausal women at high risk of fracture and with no history of myocardial infarction or stroke. EVENITY is a novel bone-builder with a dual effect that increases bone formation and to a lesser extent reduces bone resorption (or bone loss).
"After a fracture, postmenopausal women with osteoporosis are five times more likely to fracture in the subsequent year,1 and these fractures can be life-changing," said David M. Reese, M.D., executive vice president of Research and Development at Amgen. "We are pleased by the Committee's opinion because we believe EVENITY is an important therapeutic development for osteoporosis, and we look forward to the European Commission's decision later this year."
The CHMP's recommendation will now be reviewed by the European Commission (EC), which has the authority to approve medicines for use throughout the European Union. A European Commission decision is expected by year-end 2019.
"Post-menopausal osteoporosis and fragility fractures are significant women's health issues that are far too often overlooked, with evidence suggesting that an estimated 77 percent of women aged 67 or older remain undiagnosed and untreated in the first 6 months after a fracture.2 This is why new treatment options are so important," said Dr. Pascale Richetta, head of bone and executive vice president, UCB. "We believe that the Committee's positive opinion is an important step forward to help improve the lives of postmenopausal women with severe osteoporosis who are at high risk of fragility fractures."
EVENITY is approved in U.S. for the treatment of osteoporosis in postmenopausal women at high risk for fracture.3 EVENITY is also approved in Japan and South Korea for the treatment of osteoporosis for women and men at high risk for fracture, in Canada for the treatment of osteoporosis for postmenopausal women at high risk for fracture, and in Australia for the treatment of osteoporosis in postmenopausal women at high risk of fracture and as a treatment to increase bone mass in men with osteoporosis at high risk of fracture. 4-7
About EVENITY® (romosozumab)
EVENITY is a bone-forming monoclonal antibody. It is designed to work by inhibiting the activity of sclerostin, which simultaneously results in increased bone formation and to a lesser extent decreased bone resorption. The EVENITY development program includes 19 clinical studies that enrolled approximately 14,000 patients. EVENITY has been studied for its potential to reduce the risk of fractures in an extensive global Phase 3 program that included two large fracture trials comparing EVENITY to either placebo or active comparator in nearly 11,000 postmenopausal women with osteoporosis. Amgen and UCB are co-developing EVENITY.
About the Pivotal EVENITY Clinical Trials
FRAME (Fracture study in postmenopausal women with osteoporosis) is a randomized, double-blind, placebo-controlled study that evaluated 7,180 postmenopausal women with osteoporosis at risk for fracture. The study evaluated the effectiveness of EVENITY treatment (210 mg, administered monthly), compared with placebo, in reducing the risk of new vertebral fractures through 12 months. The study also evaluated the effectiveness of treating with EVENITY for 12 months followed by denosumab for 12 months, compared with placebo followed by denosumab, in reducing the risk of new vertebral fractures through 24 months.
ARCH (Active-controlled fracture study in postmenopausal women with osteoporosis at high risk of fracture) is a randomized, double-blind, alendronate-controlled study of EVENITY in 4,093 postmenopausal women with osteoporosis and previous fracture history. This event-driven study evaluated 12 months of EVENITY treatment (210 mg, administered monthly), followed by at least 12 months of alendronate treatment (70 mg), compared with alendronate treatment alone, to assess its efficacy in reducing the risk of clinical fracture (non-vertebral fracture and symptomatic vertebral fracture) through the primary analysis period and the incidence of new vertebral fracture at 24 months.
BRIDGE (Placebo-controlled study evaluating the efficacy and safety of romosozumab in treating men with osteoporosis) is a randomized, double-blind, placebo-controlled study of 245 men aged 55-90 years with osteoporosis and a history of fragility fracture (excluding hip fracture) or vertebral fracture. The study evaluated the effectiveness of EVENITY treatment (210 mg, administered monthly) for 12 months, compared with placebo, in increasing bone mineral density (BMD) at the lumbar spine and the effect on BMD at the femoral neck and total hip.
About Osteoporosis-Related Fractures
Worldwide, one in three women and one in five men, over the age of 50, will suffer a fragility fracture due to osteoporosis and with an aging population these numbers will rise.8 Yet despite this, there is a large gap in the management and treatment of osteoporosis, especially in the post-fracture setting, with an estimated four out of five patients remaining undiagnosed and untreated after a fracture.9 Without proper care or access to effective intervention options, they remain at risk of painful and disabling fractures in the future.
Important U.S. Product Information
EVENITY® is indicated for the treatment of osteoporosis in postmenopausal women at high risk for fracture, defined as a history of osteoporotic fracture, or multiple risk factors for fracture; or patients who have failed or are intolerant to other available osteoporosis therapy.
The anabolic effect of EVENITY wanes after 12 monthly doses of therapy. Therefore, the duration of EVENITY use should be limited to 12 monthly doses. If osteoporosis therapy remains warranted, continued therapy with an anti-resorptive agent should be considered.
Important U.S. Safety Information
POTENTIAL RISK OF MYOCARDIAL INFARCTION, STROKE AND CARDIOVASCULAR DEATH
EVENITY® may increase the risk of myocardial infarction, stroke and cardiovascular death. EVENITY® should not be initiated in patients who have had a myocardial infarction or stroke within the preceding year. Consider whether the benefits outweigh the risks in patients with other cardiovascular risk factors. Monitor for signs and symptoms of myocardial infarction and stroke and instruct patients to seek prompt medical attention if symptoms occur. If a patient experiences a myocardial infarction or stroke during therapy, EVENITY® should be discontinued.
In a randomized controlled trial in postmenopausal women, there was a higher rate of major adverse cardiac events (MACE), a composite endpoint of cardiovascular death, nonfatal myocardial infarction and nonfatal stroke, in patients treated with EVENITYTM compared to those treated with alendronate.
Contraindications: EVENITY® is contraindicated in patients with hypocalcemia. Pre-existing hypocalcemia must be corrected prior to initiating therapy with EVENITY®. EVENITY® is contraindicated in patients with a history of systemic hypersensitivity to romosozumab or to any component of the product formulation. Reactions have included angioedema, erythema multiforme and urticaria.
Hypersensitivity: Hypersensitivity reactions, including angioedema, erythema multiforme, dermatitis, rash and urticaria have occurred in EVENITYTM-treated patients. If an anaphylactic or other clinically significant allergic reaction occurs, initiate appropriate therapy and discontinue further use of EVENITY®.
Hypocalcemia: Hypocalcemia has occurred in patients receiving EVENITY®. Correct hypocalcemia prior to initiating EVENITY®. Monitor patients for signs and symptoms of hypocalcemia, particularly in patients with severe renal impairment or receiving dialysis. Adequately supplement patients with calcium and vitamin D while on EVENITY®.
Osteonecrosis of the Jaw (ONJ): ONJ, which can occur spontaneously, is generally associated with tooth extraction and/or local infection with delayed healing, and has been reported in patients receiving EVENITY®. A routine oral exam should be performed by the prescriber prior to initiation of EVENITY®. Concomitant administration of drugs associated with ONJ (chemotherapy, bisphosphonates, denosumab, angiogenesis inhibitors, and corticosteroids) may increase the risk of developing ONJ. Other risk factors for ONJ include cancer, radiotherapy, poor oral hygiene, pre-existing dental disease or infection, anemia and coagulopathy.
For patients requiring invasive dental procedures, clinical judgment should guide the management plan of each patient. Patients who are suspected of having or who develop ONJ should receive care by a dentist or an oral surgeon. In these patients, dental surgery to treat ONJ may exacerbate the condition. Discontinuation of EVENITY® should be considered based on benefit-risk assessment.
Atypical Femoral Fractures: Atypical low-energy or low trauma fractures of the femoral shaft have been reported in patients receiving EVENITY®. Causality has not been established as these fractures also occur in osteoporotic patients who have not been treated.
During EVENITY® treatment, patients should be advised to report new or unusual thigh, hip or groin pain. Any patient who presents with thigh or groin pain should be evaluated to rule out an incomplete femur fracture. Interruption of EVENITY® therapy should be considered based on benefit-risk assessment.
Adverse Reactions: The most common adverse reactions (≥ 5%) reported with EVENITY® were arthralgia and headache.
EVENITY® is a humanized monoclonal antibody. As with all therapeutic proteins, there is potential for immunogenicity.