Swiss Summary of the Risk Management Plan (RMP) for Nucala (Mepolizumab)

Transcription

1 Swiss Summary of the Risk Management Plan (RMP) for Nucala (Mepolizumab) RMP Summary: Version 1, March 2017 EU RMP: Version 2,

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 minimize them. The RMP summary of Nucala 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 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 Nucala in Switzerland is the Arzneimittelinformation (see approved and authorized by Swissmedic. GlaxoSmithKline AG is fully responsible for the accuracy and correctness of the content of the here published summary RMP for Nucala. Page 2 of 9

3 Overview of disease epidemiology Asthma is a chronic lung disease characterized by inflammation, narrowing of the airways, and reversible airway obstruction affecting approximately 300 million patients worldwide. Although the majority of patients can be effectively treated with available asthma controller medications, a subset of patients does not respond to current standard therapy. This subset of severe asthma affects approximately 5-10% of overall asthmatic patients but is responsible for a greater percentage of associated health care costs. Severe asthma is characterized by frequent attacks, difficult to treat airway obstruction, persistent inflammation, and the need for treatment with high doses of inhaled or oral corticosteroids and/or drugs that suppress the immune system. Severe eosinophilic asthma is further characterized by too many eosinophils in the blood ( 150 cells/µl), leading to increased airways damage and worsening of your asthma. Approximately two-thirds of severe asthma patients have been reported to have too many eosinophils in the blood. Summary of treatment benefit Two studies (MEA and MEA115588) treated a total of 846 severe eosinophilic asthma patients with mepolizumab and 346 patients with placebo. The main measure of effect in these studies was decreasing the number of asthma attacks in patients with severe asthma that is driven by eosinophils and who have at least 2 asthma attacks a year even though they are taking multiple, high dose asthma medications. Patients who got mepolizumab in the studies had about half as many attacks as patients who got placebo. Another study (MEA115575) treated 69 patients with mepolizumab and 66 patients with placebo. This study included patients who were taking maximum doses of their asthma medications and were also taking regular doses of oral corticosteroids, such as prednisolone. The main measure of effect in this study was to see if mepolizumab could help reduce the total daily amount of oral corticosteroids without causing an increase in asthma symptoms or an asthma attack. Patients who got mepolizumab achieved a bigger decrease in their prednisolone dose compared to patients who got placebo. In fact, 38% of the mepolizumab treated patients were able to reduce their dose by 75% or more compared to 19% of patients who received placebo. Unknowns relating to treatment benefits Patients in these studies were mostly white and at least 18 years old. There is no evidence to suggest mepolizumab would work any differently in non-white patients or children. These studies excluded patients who were pregnant or breast-feeding so there is little information about mepolizumab treatment in this population. Summary of safety concerns Important identified risks Risk What is known Preventability Allergic reactions and allergic-like reactions caused by NUCALA. Allergic reactions (including swelling of the face, lips, mouth or tongue; wheezing, difficulty in breathing or shortness of breath; low blood pressure with fainting, The doctor s prescribing information states that an allergic reaction can occur in patients receiving NUCALA. Page 3 of 9

4 Risk What is known Preventability dizziness or light headedness; rash; and itchy raised bumps or hives) have been reported with NUCALA but these reactions have also been reported in people who got an injection of sterile salt water (dummy treatment-placebo). Patients should be told about the symptoms of these reactions and the importance of telling a doctor right away if these symptoms occur. Patients should also be told that some of these reactions can be serious and that the beginning of symptoms can be delayed by hours or days after an injection. Reactions around the area of the skin where the shot of NUCALA was given. Reactions around the area of the skin where the infection of NUCALA was given have been reported in 8 out of every 100 patients. These same types of reactions were also reported in 3 out of every 100 patients who got an injection with placebo. The most common symptoms were pain, redness, swelling, itching, and burning. These reactions were not severe and most resolve within a few days. The doctor s prescribing information states that reactions around the area of the skin where the shot of NUCALA was given can occur. Important potential risks Risk An attack from the body s natural defences to illness and infection (Immunogenicity) What is known (Including reason why it is considered a potential risk) All medicines like NUCALA may cause the body s natural defences to illness and infection to attack NUCALA (immune response) and this can be monitored by measuring a protein in the body called an antibody. If this antibody is present, it may decrease the effectiveness of NUCALA to control asthma and it may increase the chance of side effects such as allergic reactions. The presence of antibodies was tested during the studies of NUCALA in patients with severe asthma. Overall, 6 out of every 100 patients tested positive for these antibodies. However, the presence of these antibodies did not appear to lower the effectiveness of NUCALA to control asthma or cause side effects in most people. Increased infections Infections (especially serious infections) are a potential concern with any new medicine like NUCALA that lowers certain white blood cells, called eosinophils, in the body. Patients who have low white blood cell counts have a higher chance of developing an infection, though this appears to be less likely with lowered eosinophils. Additionally, many severe asthma patients are taking other medicines that affect the body s ability to fight infection. Infections Page 4 of 9

5 Risk What is known (Including reason why it is considered a potential risk) were monitored during the studies that tested NUCALA in patients with severe asthma. The occurrence of all infections and serious infections occurred in similar numbers of patients who got NUCALA compared to those who got placebo. Three types of infections were more common with NUCALA although they weren t serious or severe. Lower respiratory tract infections occurred in 3 out of every 100 patients with severe asthma who got NUCALA and 2 out of every 100 patients who got placebo. Urinary tract infections occurred commonly in 4 out of every 100 patients with severe asthma who got NUCALA and 2 out of every 100 patients who got placebo. Pharyngitis occurred commonly in 3 out of every 100 patients with severe asthma who got NUCALA and 2 out of every 100 patients who got placebo. Cancers Cancers are a potential concern with NUCALA that lowers eosinophils, and with medicines that may affect the body s immune system. Cancers were monitored during the studies that tested NUCALA in patients with severe asthma. Cancers occurred in similar numbers of patients who got NUCALA compared to those who got placebo and the types of cancers were similar to those occurring generally in people no matter what medicines they take. Side effects of the heart and blood vessels Worsening of asthma when NUCALA treatment is stopped Effects on the heart and blood vessels are a potential concern with all new medicines and were monitored during the studies that tested NUCALA in patients with severe asthma. In general, side effects of the heart and blood vessels occurred in similar numbers of patients who got NUCALA compared to those who got placebo. In one dose-ranging study in patients with severe asthma, side effects of the heart occurred more often in the patients who got NUCALA compared to the patients who got placebo. This finding wasn t seen in other studies in patients with severe asthma or other diseases. Worsening of disease symptoms when a medicine is stopped is a potential concern with all medicines and was monitored during the studies that tested NUCALA in patients with severe asthma. Worsening of asthma after NUCALA treatment was stopped occurred in similar numbers of patients who got NUCALA compared to those who got placebo. Page 5 of 9

6 Missing information Risk Patients who are pregnant or who are currently breastfeeding Patients who are less than 18 years of age Elderly patients Patients with parasites or at high risk of infection of parasites Limited information in long-term safety information on the dose of NUCALA 100 mg given as a shot What is known There is limited information on the safety of NUCALA in pregnant women so it is difficult to know whether mepolizumab increases the chance of problems with pregnancies or the baby. Animals that got NUCALA did not have an increase in problems with their pregnancy or baby. A patient should be instructed to tell her doctor if she becomes pregnant whilst taking NUCALA. A pregnancy study is planned in North America to collect information on pregnancy outcomes and birth defects on a voluntary basis in women with asthma who have received NUCALA. This information will be compared to a group of pregnant women with asthma who don t receive NUCALA. Nineteen patients aged 12 to17 years were studied in severe asthma studies with NUCALA. The information is limited but the safety of NUCALA and how the body handled the drug in these patients was similar to patients 18 years of age and older. Children with severe asthma under 12 years of age have not been studied. A study in children 6 to 11 years of age is planned to test how the body will handle NUCALA in a younger group of children. There is limited information on the use of NUCALA in patients who are 65 years old or older; but the safety of NUCALA and how the body handled the drug did not appear to differ based on age. NUCALA lowers a blood cell in the body called an eosinophil. Eosinophils may affect how the body fights infections with parasites. Patients infected with parasites were not studied in the severe asthma trials that tested NUCALA. Patients infected with parasites should be treated for the infection before getting NUCALA. If a patient is getting NUCALA and gets a parasite infection, the doctor may temporarily stop NUCALA if the parasite infection doesn t respond to treatment. There is limited information of the long-term effects of NUCALA on patients who have received 100 mg given by a shot. The average length of time that patients received NUCALA 100 mg given by a shot is 8 months in the studies completed so far. Some patients have received the dose for up to 17 months. There are studies ongoing in patients with severe asthma to continue to investigate the safety of NUCALA for longer periods of time. Summary of additional risk minimisation measures by safety concern All medicines have a Summary of Product Characteristics (SmPC) which provides physicians, pharmacists and other health care professionals with details on how to use the medicine, the risks and recommendations for minimising them. An abbreviated version of this in lay language is provided in the form of the package leaflet (PL). The measures in these documents are known as routine risk minimisation measures. Page 6 of 9

7 This medicine has no additional risk minimisation measures. 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 Pregnancy Surveillance Study (Category 3) To evaluate outcomes for pregnant women with asthma and their infants exposed to mepolizumab Adverse impact of mepolizumab exposure to pregnancy outcomes and birth defects Planned Final Report 2Q 2024 MEA115666: A multi-centre, openlabel, long-term safety study of mepolizumab in asthmatic subjects who participated in the MEA trial (Category 3) : A Multi- Centre, Open- Label, Study of Mepolizumab in a Subset of Subjects with a History of Life Threatening/Serio usly Debilitating Asthma Who Participated in the MEA Trial (Category 3) To describe the long-term safety profile of mepolizumab To provide extended treatment with mepolizumab to subjects from study MEA and to further describe long-term dafety in these subjects. Long-term safety Ongoing Final report 2018 Long-term safety Ongoing Final report 2018 Study : A study to evaluate the efficacy of mepolizumab 100 mg subcutaneous (SC) every 4 weeks versus placebo on health-related quality of life (HR- QoL) and FEV1 in To assess the safety and tolerability of mepolizumab compared to placebo in severe asthma Ongoing November Final Study Report Page 7 of 9

8 Study/activity (including study number) Objectives Safety concerns /efficacy issue addressed Status Planned date for submission of (interim and) final results adult and adolescent subjects with severe eosinophilic asthma. Studies which are a condition of the marketing authorisation None of the above studies is a condition of the marketing authorisation. Summary of changes to the Risk Management Plan over time Major Changes to the Risk Management Plan Over Time Version Date Safety Concerns Comment April 2015 Limited data in elderly patients added as missing information Limited data in pregnancy- pregnancy registry made a category 3 PASS August 2015 Limited long-term safety data- MEA (OLE study) included as a category 3 study Changes made based 120 responses from CHMP Changes made based on 180 day responses from CHMP Limited data in pregnancy- Milestone dates for pregnancy surveillance study added Limited data in patients with parasitic infections- TFUQ for spontaneous reports of parasitic infections added as a pharmacovigilance measure MEA final study data added where appropriate September 2015 All: Integrated data from the first interim of Changes made following CHMP review of GSK Page 8 of 9

9 Version Date Safety Concerns Comment MEA and the final MEA study report added to the appropriate sections. responses to the 180 day questions and Oral Explanation. Updated SPC language added September 2015 Limited long-term safety data (OLE study) included as a category 3 study Changes made at the request of the CHMP First approved version of the EU RMP 2 26 May 2016 Limited data in pregnancy Update to the final report date for the pregnancy surveillance study and final protocol provided This summary was last updated in March Page 9 of 9