Swiss Summary of the Risk Management Plan (RMP) for Parsabiv (Etelcalcetide)

Transcription

1 Swiss Summary of the Risk Management Plan (RMP) for Parsabiv (Etelcalcetide) RMP Summary: Version 1, November 2017 EU RMP: Version 1.0, November 2016 Page 1 of 6

2 The Risk Management Plan (RMP) is a comprehensive document submitted as part of the application dossier for market approval of a medicine. The RMP summary contains information on the medicine's safety profile and explains the measures that are taken in order to further investigate and follow the risks as well as to prevent or minimise them. The RMP summary of Parsabiv is a concise document and does not claim to be exhaustive. As the RMP is an international document, the summary might differ from the Arzneimittelinformation / Information sur le médicament approved and published in Switzerland, e.g. by mentioning risks occurring in populations or indications not included in the Swiss authorization. Please note that the reference document which is valid and relevant for the effective and safe use of PARSABIV in Switzerland is the Arzneimittelinformation/ Information sur le médicament (see approved and authorized by Swissmedic. AMGEN Switzerland AG is fully responsible for the accuracy and correctness of the content of the published summary RMP of Parsabiv. Page 2 of 6

3 Overview of disease epidemiology Parsabiv is used to treat secondary hyperparathyroidism in adults which is caused by the release of too much parathyroid hormone by the parathyroid glands as a result of a number of abnormalities that occur with chronic (long-term) kidney disease. Parsabiv works by controlling the levels of parathyroid hormone, calcium, and phosphorus in the blood. Most patients with end-stage kidney disease will have secondary hyperparathyroidism by the time they are needing hemodialysis. In Europe, the incidence of patients needing dialysis is between 77 to 194 patients per million (depending on which country you live in). Summary of treatment benefits The 2 main studies of Parsabiv in the treatment of secondary hyperparathyroidism involved a total of 1013 male and female adult patients aged between 21 and 93 years with chronic kidney disease who were undergoing hemodialysis. The patients were randomly assigned to receive either Parsabiv (503 patients) or placebo (513 patients) TIW immediately after dialysis. The proportion of patients with a greater than 30% reduction in average parathyroid hormone levels was greater in patients treated with Parsabiv (75% [380 patients]) compared with placebo (9% [46 patients]). The average parathyroid hormone levels were calculated during weeks 20 to 27 and were compared with the parathyroid levels measured at the start of the study. Unknowns relating to treatment benefits Patient demographics (eg. age, sex, and race) in the main studies were well balanced between the 2 treatment groups (Parsabiv/etelcalcetide and placebo) and approximately 1/3 of patients were 65 years or older. Analysis of further data, including parathyroid hormone level at study start, prior use of cinacalcet hydrochloride (another medicine used to treat secondary hyperparathyroidism in patients with chronic kidney disease), and race, showed that Parsabiv was consistently more effective than placebo in reducing PTH. It is not confirmed that there is a positive effect on mortality, however there is clear improvement in the metabolic disorders due to end-stage-renal disease. Page 3 of 6

4 Summary of safety concerns Important identified risks Risk What is known Preventability Low calcium in the blood (hypocalcemia) Parsabiv may cause low calcium in the blood which can cause numbness, muscle pain, cramping, spasms, twitches, and in rare cases, there may be seizures (convulsions). Generally patients recover when the low calcium level in their blood is treated. Patients whose serum calcium is not above the lower limit of the normal range should not be started on Parsabiv. Patients should have their calcium levels checked within 1 week of starting Parsabiv and monitored carefully during treatment. Those chronic kidney disease patients receiving dialysis can be given calcium containing phosphate binders or supplements, vitamin D and/or their dialysate adjusted to manage their blood calcium levels. If patients have previously received cinacalcet, they should not start Parsabiv until 7 days after the last dose of cinacalcet hydrochloride and when serum calcium is above the lower limit of the normal range. Worsening heart failure The role of low serum calcium in the development of worsening of heart failure has not been established; however, rapid or prolonged hypocalcemia may potentially reduce the ability for the heart to contract particularly in patients with impaired heart function. Patients with a history of congestive heart failure should have their calcium levels monitored carefully whilst on treatment with Parsabiv. A disturbance of the heart s electrical system associated with low levels of blood calcium (QT prolongation secondary to hypocalcemia) Low blood calcium can potentially result in an abnormal ventricular rhythm (abnormal heart rhythms that originate in the lower chambers of the heart). Patients who have other risk factors such as those with heart rhythm problems since birth or patients taking other medicines that are known to cause heart rhythm effects should notify their doctor. Parsabiv should be used with caution in patients with congenital (from birth) long QT syndrome, previous history of QT prolongation, family history of long QT syndrome or sudden cardiac death, and other conditions that predispose to QT prolongation and ventricular arrhythmia. Page 4 of 6

5 Important potential risks Risk Unusually fast or pounding heart beat (ventricular arrhythmias) What is known Low blood calcium can affect ventricular rhythm. Cases of ventricular arrhythmia have been reported in patients taking Parsabiv. Allergic reaction (infusion and hypersensitivity reactions) The rates of allergic reactions such as rash, itching, swelling of the face and lips, wheezing or difficulty breathing were balanced between subjects receiving Parsabiv and placebo. Seizures (convulsions) Convulsions or seizures can potentially happen when blood calcium levels are low; they are most likely to occur in cases where the blood calcium levels fall significantly. Fractures Parsabiv acts to lower parathyroid hormone concentrations in the blood. Patients who have undergone dialysis and whose parathyroid levels are too low for too long may be at an increased risk of low bone turnover with very little new bone formation. This may increase the risk of certain types of fractures. Co-administration of Parsabiv and cinacalcet HCl (including other drugs that reduce calcium) Cinacalcet hydrochloride is also a medicine that reduces parathyroid hormone and subsequently lowers calcium levels in the blood. The effects of taking cinacalcet hydrochloride and Parsabiv together are not known yet, but there is the potential for higher risk of the occurrence of low calcium levels due to additive effect of these two drugs. Missing information Risk Use in pregnancy and lactation What is known The effects of Parsabiv in pregnant women are unknown. In an animal study in which the mother received very high doses of Parsabiv while pregnant, decreased body weight and a small delay in growth were seen in the unborn offspring. Summary of risk minimisation measures by safety concern All medicines have a summary of product characteristics (SmPC) which provides physicians, pharmacists and other healthcare professionals with details on how to use the medicine, and also describes the risks and recommendations for minimising them. Information for patients is available in lay language in the package leaflet. The measures listed in these documents are known as routine risk minimisation measures. The Summary of Product Characteristics and the Package leaflet for Parsabiv can be found in Parsabiv s European public assessment reports (EPAR) page. This medicine has no additional risk minimization measures. Page 5 of 6

6 Planned post-authorisation development plan List of studies in post-authorisation development plan Study/activity (including study number) Objectives Safety concerns /efficacy issue addressed Status Planned date for submission of (interim and) final results A Phase 3, Multicenter Single-arm Extension Study to Describe the Longterm Safety of AMG 416 in the Treatment of Secondary Hyperparathyroidism in Subjects With Chronic Kidney Disease on Hemodialysis Primary: To characterize the long-term safety and tolerability of etelcalcetide in the treatment of secondary HPT in subjects with CKD on hemodialysis Secondary: To characterize PTH, total serum albumin cca, and serum phosphorous values. Descriptive efficacy data will also be provided. This study will provide a more complete dataset to evaluate the long-term efficacy of Parsabiv/etelcalcetide Ongoing Final report anticipated Q Studies which are a condition of the marketing authorisation None Summary of changes to the risk management plan over time Major changes to the Risk Management Plan over time Not applicable. This summary was last updated in November Page 6 of 6