Fasenra. 30 mg, solution for injection. Summary of the Risk Management Plan (RMP) for Fasenra (Benralizumab)

Transcription

1 Fasenra 30 mg, solution for injection Summary of the Risk Management Plan (RMP) for Fasenra (Benralizumab) Document Version: 1.0 Document Date: 08-June-2018

2 Summary of the risk management plan (RMP) for Fasenra (Benralizumab) 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 Fasenra 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 Fasenra in Switzerland is the Arzneimittelinformation/ Information sur le médicament (see approved and authorized by Swissmedic. AstraZeneca AG is fully responsible for the accuracy and correctness of the content of the published summary RMP of Fasenra. Overview of disease epidemiology The Global Initiative for Asthma 2016 reports about 300 million people having asthma, with the numbers ranging from 1% to 16% of the population in different countries. It causes more than 346,000 deaths each year. Asthma patients are evaluated by the frequency and severity of their symptoms, how much asthma impairs their lives, and how much medicine they use. Patients with severe uncontrolled asthma have a high frequency of the most severe symptoms, which causes them to limit their activities and be very dependent on their rescue asthma medications. A research study reported 45% of people with asthma in Europe had uncontrolled asthma. Poorly controlled asthma places a significant burden on patients, and those with this condition are the main users of healthcare resources including ER visits and hospitalisations. Summary of treatment benefits Benralizumab is given by injection under the skin. The benefits of benralizumab in severe eosinophilic asthma that was not well controlled by previous treatment have been shown in 3 main studies, in which it was compared with a placebo (dummy) injection. The first study (CALIMA) involved 866 adults given benralizumab every 4 or every 8 weeks for 56 weeks, in addition to their regular asthma medicines. The second study (SIROCCO) involved 797 adults who were given benralizumab every 4 or every 8 weeks for 48 weeks, in addition to their regular asthma medicines. The main measure of effectiveness in these studies was the number of severe attacks or exacerbations of asthma that occurred during treatment, which were reduced by about one third to one half in patients who were given benralizumab. Additionally, there was evidence of an improvement in lung function and asthma symptoms, important measures of benefit. The third study (ZONDA) involved 145 patients with asthma which was severe enough to need regular treatment with OCS such as prednisone. The main measure of effectiveness was how much the corticosteroid dose could be reduced using benralizumab compared with placebo after 28 weeks of treatment. Approximately two-thirds of the patients given benralizumab were able to reduce their daily corticosteroid dose by more than 50% compared with approximately one-third of patients given placebo. More than one-third of benralizumab-treated patients were able to reduce their corticosteroid use by 90% Page 2 of 6

3 to 100%, compared with approximately 10% of those patients given placebo. Unknowns relating to treatment benefits Patients in these studies were mostly white and 18 years of age or older. There is no evidence to suggest that benralizumab would work any differently in non-white patients or in younger patients. The studies excluded patients who were pregnant or breastfeeding, so there is little information about treatment with benralizumab in these patients. Summary of safety concerns This section presents a summary of important identified risks, important potential risks, and missing information, these are defined as follows: An important identified risk is an untoward event for which there is enough evidence for it to be linked with the medicine of interest, and where the possibility of that event occurring could lessen the potential benefits of taking the medicine. An important potential risk is an untoward occurrence for which there is some reason for suspicion of a link with the medicine of interest but where this link has not been confirmed. Inclusion of information relating to a potential risk should not be taken to imply that causal association with the use of benralizumab has been established. Missing information is information about the safety of a medicine which is not available when the medicine was approved for sale. This may represent a gap in the ability to predict the safety of the medicine on particular topics after the medicine has been approved. There are no important identified risks to report at this time. Important potential risks are summarized in Table 1 below. Table 1: Important potential risks Risk What is known (including reason why it is considered a potential risk) Risk of serious infection that may lifethreatening, or requiring antibiotics given through bloodstream, or hospitalisation Benralizumab causes a decrease in the eosinophils, which are a type of white blood cells that may help to fight infections. Many patients with asthma are already on medicines that affect the body s ability to fight infection. There is a potential risk of occurrence of serious infections when using benralizumab. Serious infections were monitored during the benralizumab studies in patients. Serious infections occurred in similar numbers in patients who received benralizumab as compared to those who received placebo. Page 3 of 6

4 Risk of helminth infection Helminth is a term used to describe types of parasitic worms that live in the gut. Benralizumab reduces eosinophils, which are a type of white blood cell that may help the body to fight helminth infections. Therefore, there is a potential risk for the occurrence of helminth parasitic infections when using benralizumab. There have been no confirmed reports of helminth infection in the Phase 3 benralizumab studies. Serious hypersensitivity reactions including anaphylaxis/anaphylactic reactions Hypersensitivity is a term used to describe the situation when the body's normal immune response is excessive and undesirable, which can result in damage. Such a response can take place when the immune system encounters something unusual (e.g., infection or the injection of something). Therefore, benralizumab injections could cause these types of allergic reactions, which may be severe and even life-threatening. Hypersensitivity reactions were monitored during the benralizumab studies in patients. The hypersensitivity reactions occurred in similar numbers in patients who received benralizumab as compared to those who received placebo. Cancer (Malignancy) A normal immune system is part of the body's defence against cancer. Because benralizumab targets the immune system (in the treatment of asthma), it is possible that it may alter the body's ability to fight cancers. However, to date there is no suggestion from clinical trials that this is the case, and there have been no reports of cancer that were considered to be related to benralizumab. Table 2: Missing information Risk Risk during pregnancy and breast feeding Long-term use of 30 mg dose administered as injection under the skin What is known Use of benralizumab during pregnancy and breastfeeding has not been specifically studied and whether there is any risk to an unborn baby is not known. Limited information is available on the long-term use of benralizumab 30 mg given as injection under the skin in patients. The average duration that the patients received this dose was up to 1 year in completed studies. Studies are still ongoing in patients to investigate the safety of benralizumab for longer duration. Summary of risk minimisation measures by safety concern All medicines have a product information which provides physicians, pharmacists, and other healthcare professionals with details on how to use the medicine, the risks and recommendations for minimising them. The measures in these documents are known as routine risk minimisation measures. Page 4 of 6

5 The product information for benralizumab can be found on This medicine has no additional risk minimisation measures. Planned post-authorisation development plan Two ongoing, studies (BORA and MELTEMI) are being conducted to further characterise the long-term safety profile of the 30 mg benralizumab SC dose. In addition, a pregnancy registry study is planned to be conducted. Table 3: List of studies in post authorisation development plan Study/activity (including study number) BORA (D3250C00021) MELTEMI (D3250C00037) Objectives To assess the safety and tolerability of 2 dosing regimens of benralizumab for (1) adult patients during the 56-week treatment period and through the follow-up period (16 weeks from day of last dose) and (2) adolescent patients during the 108-week treatment period and through the follow-up period (16 weeks from day of last dose) To assess the safety and tolerability of 2 dosing regimens of benralizumab for adult patients Safety concerns /efficacy issue addressed Important Potential Risks: Serious infections, malignancies, helminth infections, serious hypersensitivity reactions including anaphylaxis/anap hylactic reactions Missing information: Safety profile in pregnancy/lactate on, long-term safety Important Potential Risks: Serious infections, malignancies, helminth infections, serious hypersensitivity reactions including anaphylaxis/anap hylactic reactions Missing information: Safety profile in pregnancy/lactati on, long-term safety Status Ongoing Ongoing Planned date for submission of (interim and) final results Final study report Completion planned Q Final study report Completion planned Q Page 5 of 6

6 The Benralizumab Pregnancy Exposure Study: A VAMPSS Post- Marketing Surveillance Study To monitor planned and unplanned pregnancies exposed to benralizumab and to evaluate the possible teratogenic effect of this medication relative to the primary pregnancy outcome of major birth defects and the secondary pregnancy outcomes of preterm delivery, small for gestational age infants, spontaneous abortion, and stillbirth. Missing information: Safety profile in pregnancy/lactation Planned Protocol will be provided within 4 months after EC decision 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 This section is not applicable. Page 6 of 6