Swiss Summary of the Risk Management Plan (RMP) for. Vosevi, film-coated tablets

Transcription

1 Swiss Summary of the Management Plan (RMP) for, film-coated tablets (Sofosbuvir/Velpatasvir/Voxilaprevir Fixed-Dose Combination) 400mg/100mg/100mg Version 1.0 (February 2018) final Based on EU RMP version 1.0 (July 2017) Gilead Sciences International Limited Granta Park, Abington Cambridge CB21 6GT United Kingdom

2 The 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 VOSEVI 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 VOSEVI in Switzerland is the Arzneimittelinformation/ Information sur le médicament (see approved and authorized by Swissmedic. Gilead Sciences International Limited is fully responsible for the accuracy and correctness of the content of the published summary RMP of VOSEVI. Overview of disease epidemiology Hepatitis C is a liver disease that results from infection with the hepatitis C virus (HCV). It can range in severity from a mild illness lasting a few weeks to a serious, lifelong illness that results in death. Hepatitis C is usually spread when blood from a person infected with the HCV enters the body of someone who is not infected. Today, many people become infected with HCV by sharing needles or other equipment to inject drugs. Hepatitis C can be either acute or chronic. Acute HCV infection is a short-term illness that occurs within the first 6 months after someone is exposed to HCV. Sometimes acute HCV infection heals with no treatment, but most people with acute HCV infection develop chronic HCV infection. Chronic HCV infection is a serious disease that may lead to scarring of the liver (liver cirrhosis), liver disease that is not reversible (for example, end-stage liver disease), and/or liver cancer. Worldwide, approximately 170 million people have HCV infection and 3 to 4 million people are newly infected with HCV every year. The number of people with HCV infection varies in different parts of the world. Countries in Africa and Asia have the highest reported HCV infection rates. Countries in North America, Western Europe, and Australia have lower reported HCV infection rates. In general, the number of people with chronic HCV infection increases with age, the number of women with chronic HCV infection is lower than the number of men with chronic HCV infection, and people of African descent seem to have a higher rate of chronic HCV infection than Caucasians and Hispanic whites. The HCV is grouped into at least 6 different categories, called genotypes. The most common genotype in North America and Europe is genotype 1 followed by genotypes 2 and 3. Genotype 4, 5, and 6 HCV infections are most common in the Middle East, South Africa, and Southeast Asia. Although HCV-related liver disease is a leading cause of mortality in adults and is the primary reason for liver transplantation in many developed countries, the vast majority of carriers die with, rather than from, this infection. Worldwide, as many as 500,000 deaths occur from hepatitis C-related diseases, which include liver cirrhosis and liver cancer, every year. There are now many effective therapies that cure the majority of patients that are treated. However, there is still a small proportion of patients that fail treatment and remain infected with HCV. Assuming approximately 1 million patients have received a SOF-containing regimen worldwide and assuming that 95-99% of all patients are cured, it is estimated that there are approximately 10,000-50,000 patients who Based on EU RMP v1.0 July 2017 Page 2 of 6

3 have failed prior direct acting antiviral (DAA) based therapy. These patients currently have very limited treatment options. Summary of treatment benefits In two studies (POLARIS-1 and POLARIS-4), a total of 445 patients with chronic hepatitis C virus (HCV) infection who had failed previous treatment for chronic HCV infection, received sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) for 12 weeks. In two other studies (POLARIS-2 and POLARIS-3), a total of 611 patients who had never been treated for chronic HCV infection, received SOF/VEL/VOX for 8 weeks. The main measure of effectiveness was the number of patients who had no detectable virus in their blood 12 weeks after the end of treatment and could therefore be considered cured. SOF/VEL/VOX was effective at curing patients with chronic HCV. In POLARIS-1, the cure rate was 96.2% (253 out of 263). In POLARIS-4, the cure rate was 97.3% (177 out of 182). In POLARIS-2, the cure rate was 95% (476 out of 501). In POLARIS-3, the cure rate was 96.4% (106 out of 110). Unknowns relating to treatment benefits SOF/VEL/VOX has not been studied in children, in women who are pregnant or breastfeeding, or in patients who are also suffering from HBV infection or HIV infection. Summary of safety concerns Important identified risks What is Known Preventability Very slow heartbeat when amiodarone is used together with SOF/VEL/VOX Flare of hepatitis B virus (HBV) in patients with HCV/HBV coinfection Some people have had very slow heartbeat when sofosbuvir is used with amiodarone and other direct acting antivirals with or without other drugs that lower your heartbeat An increase in levels of hepatitis B virus during treatment of hepatitis C virus has occurred in a small number of patients with underlying hepatitis B infection. In some cases hepatitis B virus has been associated with changes in liver function. SOF/VEL/VOX should not be used with amiodarone. If used, patients should be monitored for early symptoms. Patients who have a current hepatitis B infection or previously had hepatitis B should be closely monitored by their doctors. Before starting treatment, all patients should be tested to see if they hepatitis B virus. Important potential risks Taking SOF/VEL/VOX with rifampicin, rifapentine, St. John s wort or efavirenz Taking SOF/VEL/VOX with acid reducing medication What is Known (Including Reason Why it is considered a Potential ) Rifampicin, rifapentine and St. John s wort lower the levels of SOF/VEL/VOX in the blood, which could lead to SOF/VEL/VOX not being effective in the treatment of HCV infection. Efavirenz is expected to do the same. SOF/VEL/VOX should not be used with rifapentine, rifampicin, St. John s wort or drugs containing efavirenz. Omeprazole (or a similar acid reducing medicine) might lower the levels of SOF/VEL/VOX in the blood, which could lead to SOF/VEL/VOX not being effective in the treatment of HCV infection. Limit the dose of the acid-reducing medicine to a dose that is equal to an omeprazole dose of Based on EU RMP v1.0 July 2017 Page 3 of 6

4 Taking SOF/VEL/VOX with rosuvastatin Taking SOF/VEL/VOX with digoxin or dabigatran Taking SOF/VEL/VOX with ciclosporin Taking SOF/VEL/VOX and a drug containing tenofovir Return of hepatocellular carcinoma (HCC) (a type of liver cancer) in patients who have had HCC previously Development of HCC What is Known (Including Reason Why it is considered a Potential ) 20 mg. If SOF/VEL/VOX is used with rosuvastatin, rosuvastatin levels might increase to a level which could lead to problems in muscles, blood, and kidneys. SOF/VEL/VOX should not be used with rosuvastatin. Digoxin or dabigatran can be used with SOF/VEL/VOX, but the digoxin/dabigatran levels might increase, which could lead to digoxin/dabigatran related side effects. The physician should perform therapeutic monitoring if digoxin is used or clinical monitoring if dabigatran is used with SOF/VEL/VOX. ciclosporin may increase the levels of SOF/VEL/VOX. SOF/VEL/VOX should not be used with ciclosporin. People with both the HCV virus and the HIV virus are coinfected and might take medicines for both diseases. Drug treatments for HIV infection may sometimes contain TDF. The combination of SOF/VEL/VOX and TDF can make the TDF levels rise, which might lead to kidney problems, which can sometimes be serious or fatal. TDF has been associated with kidney problems, including damage to kidney tubule cells, kidney failure, kidney inflammation, and increases in creatinine in blood. The frequency of kidney problems is very low: in clinical trials involving TDF, the frequency of increased creatinine was 0.2% (1 in 500 patients) and of kidney failure was 0.06% (3 in 5000 patients). factors for kidney problems include advanced HIV disease (low cluster of differentiation [CD4] count at the start of treatment), low weight, older age, kidney problems before starting therapy, use of other medicines that are damaging to kidneys, high blood pressure, and also being infected with hepatitis C. Kidney problems are preventable by carrying out blood tests for kidney function at the start of treatment and during treatment and by avoiding use of other medicines that may damage the kidney. HCC has been reported in some patients who have previously had HCC while taking drugs used to treat hepatitis C virus (direct acting antivirals). It is unclear whether hepatitis C direct acting antivirals increase the risk of HCC returning in patients who previously had HCC and a study is being planned to investigate this. The risk has not yet been confirmed. Some patients have developed HCC while taking drugs used to treat hepatitis C virus (direct acting antivirals). HCC is a known complication of hepatitis C virus especially in the presence of advanced liver disease. It is unclear whether hepatitis C direct acting antivirals increase the risk of developing HCC or not. The risk has not yet been confirmed. Missing Information Limited information on use in pregnant or breastfeeding women Limited information on use in patients What is Known The effects of SOF/VEL/VOX on a pregnant female or an unborn child are not known. As a precautionary measure, it is preferable not to use SOF/VEL/VOX during pregnancy. It is not known whether SOF, VEL or VOX are passed into human breast milk. Mothers should be instructed not to breastfeed if they are taking SOF/VEL/VOX. SOF/VEL/VOX can be given to patients with mild or moderate kidney Based on EU RMP v1.0 July 2017 Page 4 of 6

5 with severely decreased kidney function or patients requiring dialysis Limited information on use in patients with moderately or severely decreased liver function Limited information on patients who have undergone liver transplant. Development of viral resistance Limited information on use in patients with previous HCC What is Known disease. The safety information on SOF/VEL/VOX in patients with severe kidney disease or severely decreased kidney function who require dialysis is missing. A clinical study will provide information about these patients. SOF/VEL/VOX can be given to patients with mild liver disease. The safety of SOF/VEL/VOX is missing in patients with moderately or severely decreased liver function. Safety data is missing about using SOF/VEL/VOX in patients who have undergone liver transplant. A large amount of data is missing about how well the SOF/VEL/VOX tablet will work to retreat patients who were not successful with previous SOF/VEL/VOX treatment. Patients with previous HCC were not included in clinical trials. A study is being planned to assess the safety of sofosbuvir and other HCV medicines (direct acting antivirals) in patients who have previously had HCC. Summary of risk minimisation measures by safety concern All medicines have an Information for Professionals ( Fachinformation ) which provides physicians, pharmacists and other health care professionals with details on how to use the medicine, the risks and recommendations for minimizing them. An abbreviated version of this in lay language is provided in the form of the Package Leaflet ( Patienteninformation ). The measures in these documents are known as routine risk minimization measures. The current Information for Professionals and the Patient Information for can be found on Planned post-authorisation development plan List of studies in post-authorisation development plan Study/Activity (Including Study Number) Objectives Safety Concerns/Efficacy Issues Addressed Status Planned Date for Submission of (Interim and) Final Results Planned study to assess the impact of DAA treatment on the incidence of HCC recurrence To evaluate the impact of DAA treatment on the incidence of HCC recurrence Important potential risk: Recurrence of HCC Planned Interim study report Q Q GS-US A Phase 2b, Open-Label Study of 200 mg or 400 mg Sofosbuvir+RBV for 24 Weeks in Genotype 1 or 3 HCV-Infected Subjects with Renal To evaluate the safety, efficacy and pharmacokinetics of treatment with SOF+RBV for 24 weeks in subjects with chronic genotype 1 or 3 HCV infection and Missing information: Safety in patients with severe renal impairment or end-stage renal disease Started August 2018 Based on EU RMP v1.0 July 2017 Page 5 of 6

6 Study/Activity (Including Study Number) Objectives Safety Concerns/Efficacy Issues Addressed Status Planned Date for Submission of (Interim and) Final Results Insufficiency severe renal impairment GS-US A Long Term Follow-up Registry Study of Subjects Who Did Not Achieve Sustained Virologic Response in Gilead-Sponsored Trials in Subjects with Chronic Hepatitis C Infection To evaluate HCV viral sequences and the persistence or evolution of treatment-emergent viral mutations in subjects who fail to achieve an SVR after treatment with a Gilead oral antiviral containing regimen in a previous Gilead-sponsored hepatitis C study Missing information: Development of resistance Started October 2021 GS-US A Long Term Follow-up Registry for Pediatric Subjects Who Received Treatment in Gilead- Sponsored Chronic Hepatitis C Infection Trials To evaluate long-term efficacy in adolescents and children who received SOF/VEL/VOX in study GS-US Missing information: Evaluation of viral relapse in pediatric subjects. Started October 2023 Feasibility analyses on the use of existing cohort studies to assess the impact of DAA treatment on the incidence and type of de novo HCC. To evaluate the feasibility of using existing cohorts to assess the impact of DAA treatment on the incidence and type of de novo HCC Important potential risk: Emergence of HCC Planned June 2017* * In accordance with the PRAC recommendation on the Article 20 referral for HCV DAAs (EMEA/H/A-20/1438) the post approval commitment date is recorded as June 2017, although this is prior to anticipated MAA approval for SOF/VEL/VOX Studies which are a condition of the marketing authorisation The following study is a condition of the marketing authorization: Planned study to assess the impact of DAA treatment on the incidence of HCC recurrence. This summary was last updated in 02/2018. Based on EU RMP v1.0 July 2017 Page 6 of 6