Amgen and UCB Provide Regulatory Update on Status of EVENITY™ (romosozumab) in the EU
"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. Yet these patients often remain undiagnosed and untreated and could benefit from a new treatment option with 12 monthly doses to reduce their risk of a fracture," said
The opinion is based on results from a large development program including three pivotal Phase 3 studies comprised of nearly 12,000 patients: FRAME, including 7,180 postmenopausal women with osteoporosis at risk for fracture;2 ARCH, including 4,093 postmenopausal women with osteoporosis at high risk for fracture;3 and BRIDGE, including 245 men with osteoporosis.4
"We are disappointed with the CHMP opinion and believe that the body of evidence submitted supports a positive benefit:risk profile for EVENITY and its use in helping address the urgent need to improve post-fracture care and reduce the risk of painful, disabling fractures in postmenopausal women with severe osteoporosis at high risk of fracture," said Dr.
EVENITY (romosozumab-aqqg) was approved by the
About EVENITYTM (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.
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. The study evaluated the efficacy of EVENITY treatment (210 mg, administered monthly), compared with placebo, in reducing the incidence of new vertebral fractures through 12 months. The study also evaluated the efficacy of treating with EVENITY for 12 months followed by denosumab for 12 months, compared with placebo followed by denosumab, in reducing the incidence 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 efficacy 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.9 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.10 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
EVENITYTM 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
EVENITYTM may increase the risk of myocardial infarction, stroke and cardiovascular death. EVENITYTM 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, EVENITYTM 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: EVENITYTM is contraindicated in patients with hypocalcemia. Pre-existing hypocalcemia must be corrected prior to initiating therapy with EVENITYTM. EVENITYTM 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 EVENITYTM.
Hypocalcemia: Hypocalcemia has occurred in patients receiving EVENITYTM. Correct hypocalcemia prior to initiating EVENITYTM. 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 EVENITYTM.
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 EVENITYTM. A routine oral exam should be performed by the prescriber prior to initiation of EVENITYTM. 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 EVENITYTM 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 EVENITYTM. Causality has not been established as these fractures also occur in osteoporotic patients who have not been treated.
During EVENITYTM 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 EVENITYTM therapy should be considered based on benefit-risk assessment.
Adverse Reactions: The most common adverse reactions (≥ 5%) reported with EVENITYTM were arthralgia and headache.
EVENITYTM is a humanized monoclonal antibody. As with all therapeutic proteins, there is potential for immunogenicity.
Amgen Forward-Looking Statements
This news release contains forward-looking statements that are based on the current expectations and beliefs of
No forward-looking statement can be guaranteed and actual results may differ materially from those
The scientific information discussed in this news release related to
UCB Forward-Looking Statements
This press release contains forward-looking statements based on current plans, estimates and beliefs of management. All statements, other than statements of historical fact, are statements that could be deemed forward-looking statements, including estimates of revenues, operating margins, capital expenditures, cash, other financial information, expected legal, political, regulatory or clinical results and other such estimates and results. By their nature, such forward-looking statements are not guarantees of future performance and are subject to risks, uncertainties and assumptions which could cause actual results to differ materially from those that may be implied by such forward-looking statements contained in this press release. Important factors that could result in such differences include: changes in general economic, business and competitive conditions, the inability to obtain necessary regulatory approvals or to obtain them on acceptable terms, costs associated with research and development, changes in the prospects for products in the pipeline or under development by UCB, effects of future judicial decisions or governmental investigations, product liability claims, challenges to patent protection for products or product candidates, changes in laws or regulations, exchange rate fluctuations, changes or uncertainties in tax laws or the administration of such laws and hiring and retention of its employees. UCB is providing this information as of the date of this press release and expressly disclaims any duty to update any information contained in this press release, either to confirm the actual results or to report a change in its expectations.
There is no guarantee that new product candidates in the pipeline will progress to product approval or that new indications for existing products will be developed and approved. Products or potential products which are the subject of partnerships, joint ventures or licensing collaborations may be subject to differences between the partners. Also, UCB or others could discover safety, side effects or manufacturing problems with its products after they are marketed.
Moreover, sales may be impacted by international and domestic trends toward managed care and health care cost containment and the reimbursement policies imposed by third-party payers as well as legislation affecting biopharmaceutical pricing and reimbursement.
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Isabelle Ghellynck, Investor Relations, UCB
- Lindsay R, Silverman SL, Cooper C, et al. Risk of new vertebral fracture in the year following fracture. JAMA. 2001;285(3):320-323.
- Cosman F, Crittenden DB, Adachi JD, et al. Romosozumab treatment in postmenopausal women with osteoporosis. N Engl J Med 2016;375:1532-1543.
Saag KG, Petersen, J, Brandiet ML, et al. Romosozumab or alendronate for fracture prevention in women with osteoporosis. N Engl J Med 2017;377:1417–27.
- A Double-blind Study to Compare the Safety and Efficacy of Romosozumab (AMG 785) Versus Placebo in Men With Osteoporosis (BRIDGE). Available at: https://clinicaltrials.gov/ct2/show/NCT02186171?term=NCT02186171&rank=1. Accessed
January 14, 2019.
- EVENITY™ (romosozumab-aqqg) U.S. Prescribing Information https://www.pi.amgen.com/~/media/amgen/repositorysites/pi-amgen-com/evenity/evenity_pi_hcp_english.ashx
- Pharmaceuticals and Medical Devices Agency Prescription Drug Database http://www.pmda.go.jp/PmdaSearch/iyakuDetail/ResultDataSetPDF/112922_3999449G1025_1_02
Ministry of Food and Drug Safety, Import Drug License. 20190531. Health Canada. Notice of Compliance, June 2017. International Osteoporosis Foundation. Patient Brochure. http://share.iofbonehealth.org/WOD/2012/patient_brochure/WOD12-patient_brochure.pdf. Accessed June 24, 2019. International Osteoporosis Foundation. Facts and Statistics. https://www.iofbonehealth.org/facts-statistics. Accessed June 24, 2019.
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