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1 FOR PEOPLE WITH HEMOPHILIA A WITH OR WITHOUT FACTOR VIII INHIBITORS GO SEEK. GO EXPLORE. GO AHEAD. C M Y CM MY CY CMY K Discover your sense of go. Discover. What is? is a prescription medicine used for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adults and children, ages newborn and older, with hemophilia A with or without factor VIII inhibitors. What is the most important information I should know about? increases the potential for your blood to clot. Carefully follow your healthcare provider s instructions regarding when to use an on-demand bypassing agent or factor VIII, and the dose and schedule to use for breakthrough bleed treatment. may cause serious side effects when used with activated prothrombin complex concentrate (apcc; FEIBA ), including thrombotic microangiopathy (TMA), and blood clots (thrombotic events). If apcc (FEIBA ) is needed, talk to your healthcare provider in case you feel you need more than 100 U/kg of apcc (FEIBA ) total. Please see Important Safety Information, including Serious Side Effects, throughout this brochure, as well as the full Prescribing Information and Medication Guide.

2 Choosing the treatment that is right for you Choosing the treatment that is right for you is an important decision that involves careful consideration. This brochure provides you with information on, a treatment for people with hemophilia A with or without factor VIII inhibitors. Talk to your healthcare provider to see whether may be right for you. Inside, you ll find the following information: What is? 5 How it was studied 6-7 Benefits of (based on clinical trials) 8-15 C M PLEASE REMEMBER Patient experience with How it works Y CM MY CY While this brochure is meant to provide helpful information, it does not How to take Important Safety Information CMY K provide medical advice or replace conversations with your healthcare provider. Important things to know Support resources Starting a conversation with your healthcare provider Please see Important Safety Information, including Serious Side Effects, throughout this brochure, as well as the full Prescribing Information and Medication Guide. 2 3

3 Proven bleed protection for people with hemophilia A with or without factor VIII inhibitors DISCOVER PROVEN EFFECTIVE TO IN 2 INTRA-PATIENT ANALYSES, PEOPLE HAD A REQUIRING TREATMENT* COMPARED WITH NO PROPHYLAXIS (MAIN GOAL OF 2 TRIALS) COMPARED WITH BOTH PRIOR PROPHYLAXIS FVIII AND BYPASSING THERAPY REDUCE BLEEDS SIGNIFICANT REDUCTION IN TREATED BLEEDS * THE MAJORITY OF PEOPLE HAD ZERO BLEEDS REQUIRING TREATMENT * Based on information from 2 trials: adults and adolescents with factor VIII inhibitors adults and adolescents without factor VIII inhibitors Safety evaluated in the largest clinical trial program in hemophilia A with and without factor VIII inhibitors First and only prophylactic subcutaneous injection with 3 dosing options is a therapeutic antibody that works differently than other treatments, and maintains consistent drug levels *The need to treat was determined by the individual or the trial physician. may cause the following serious side effects when used with apcc (FEIBA ), including: Please see Important Safety Information, including Serious Side Effects, throughout this brochure, as well as the full Prescribing Information and Medication Guide. 4 5 Thrombotic microangiopathy (TMA). This is a condition involving blood clots and injury to small blood vessels that may cause harm to your kidneys, brain, and other organs. Get medical help right away if you have any of the following signs or symptoms during or after treatment with : confusion yellowing of skin and eyes feeling sick weakness stomach (abdomen) or back pain decreased urination swelling of arms and legs nausea or vomiting If apcc (FEIBA ) is needed, talk to your healthcare provider in case you feel you need more than 100 U/kg of apcc (FEIBA ) total.

4 How was studied THE LARGEST CLINICAL TRIAL PROGRAM OF PEOPLE WITH HEMOPHILIA A WITH AND WITHOUT FACTOR VIII INHIBITORS The 373* people also included the following ages: A TOTAL OF PEOPLE The efficacy, safety, and pharmacokinetics (movement through the body) of were evaluated in 4 trials HAVEN 3 Adults and adolescents without FVIII inhibitors HAVEN 4 Adults and adolescents with or without FVIII inhibitors HAVEN 2 Children with FVIII inhibitors (interim analysis of an ongoing trial) Safety analysis included 18 additional people who participated in a trial exploring dosing. HAVEN 1 Adults and adolescents with FVIII inhibitors 266 ADULTS 18 years and older 47 ADOLESCENTS 12 years up to less than 18 years 60 CHILDREN younger than 12 years All children had factor VIII inhibitors. *These 373 people include those who participated in the 4 pivotal clinical trials that led to approval. Safety was also evaluated in an additional 18 people who participated in a trial exploring dosing. The 373 people can also be broken down by people with and without factor VIII inhibitors: 193 PEOPLE WITHOUT FVIII INHIBITORS 180 PEOPLE WITH FVIII INHIBITORS Just over half had previously been treated with immune tolerance induction (ITI) therapy. may cause the following serious side effects when used with apcc (FEIBA ), including: Blood clots (thrombotic events). Blood clots may form in blood vessels in your arm, leg, lung, or head. Get medical help right away if you have any of these signs or symptoms of blood clots during or after treatment with : swelling in arms or legs fast heart rate numbness in your face pain or redness in your arms or legs cough up blood eye pain or swelling shortness of breath feel faint trouble seeing chest pain or tightness headache If apcc (FEIBA ) is needed, talk to your healthcare provider in case you feel you need more than 100 U/kg of apcc (FEIBA ) total. Adults and adolescents took for at least 24 weeks; children took for at least 12 weeks (interim analysis of an ongoing trial) All data were converted to an annualized bleed rate, also referred to as annual bleed rate (ABR) The main goal of all trials was to measure the number of bleeds requiring treatment (treated bleeds*) In 2 trials, was compared with on-demand (no prophylaxis) FVIII therapy in people without factor VIII inhibitors, and compared with on-demand (no prophylaxis) bypassing therapy in people with factor VIII inhibitors *The need to treat was determined by the individual or the trial physician. Individuals did not receive prophylactic therapy. Two intra-patient analyses were also conducted. In these before and after comparisons: People first used their routine prophylactic therapy for a period of time The same group of people then switched to once weekly and the results were compared Please see Important Safety Information, including Serious Side Effects, throughout this brochure, as well as the full Prescribing Information and Medication Guide. 6 7

5 PROVEN BLEED PROTECTION A before and after analysis showed a Significant reduction in treated bleeds* compared with prior prophylactic factor VIII therapy ADULTS & ADOLESCENTS WITHOUT FVIII INHIBITORS (HAVEN 3) COMPARED WITH PRIOR PROPHYLACTIC FACTOR VIII THERAPY % reduction in ABR 68 Annual Bleed Rate (ABR) 6 % fewer treated bleeds* than with prior prophylactic FVIII therapy 0 Prior prophylactic FVIII therapy (n=48) once weekly (n=48) In this before and after comparison of prophylactic factor VIII therapy and, 48 people: First took their routine prophylactic factor VIII therapy for at least 24 weeks and the results were measured They then switched to once weekly for at least 24 weeks and the results were measured and compared In this comparison, there were 68% fewer treated bleeds* on *The need to treat was determined by the individual or the trial physician. Before using, tell your healthcare provider about all of your medical conditions, including if you: are pregnant or plan to become pregnant. It is not known if may harm your unborn baby. Females who are able to become pregnant should use birth control (contraception) during treatment with. are breastfeeding or plan to breastfeed. It is not known if passes into your breast milk. Please see Important Safety Information, including Serious Side Effects, throughout this brochure, as well as the full Prescribing Information and Medication Guide. 8 9 Tell your healthcare provider about all the medicines you take, including prescription medicines, over-the-counter medicines, vitamins, or herbal supplements. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.

6 Main goal of trial delivered a substantial reduction in treated bleeds * ADULTS & ADOLESCENTS WITHOUT FVIII INHIBITORS (HAVEN 3) The majority of people taking had zero treated bleeds * ADULTS & ADOLESCENTS WITHOUT FVIII INHIBITORS (HAVEN 3) COMPARED WITH ON-DEMAND (NO PROPHYLAXIS) FACTOR VIII THERAPY % reduction in ABR over at least 24 weeks PEOPLE WITH ZERO TREATED BLEEDS * over at least 24 weeks COMPARED WITH ON-DEMAND (NO PROPHYLAXIS) FACTOR VIII THERAPY Annual Bleed Rate (ABR) % fewer treated bleeds* with once weekly than with on-demand FVIII therapy PEOPLE WITH ZERO TREATED BLEEDS * 56 % vs. 0 % 56% of people who took once weekly had zero bleeds (n=36) vs. 0% of those who took on-demand FVIII therapy (n=18) The majority of people who took once every 2 weeks also had zero bleeds (60%, n=35) Individuals did not receive prophylactic factor VIII therapy. 5 0 On-demand FVIII therapy (n=18) 2 once weekly (n=36) COMPARED WITH PRIOR PROPHYLACTIC FACTOR VIII THERAPY 54 % vs. 40 % Consistent reduction in ABR seen with once every 2 weeks (97%, n=35) vs. on-demand factor VIII therapy (n=18). 54% of people who took once weekly had zero bleeds (n=48) vs. 40% when they took their prior prophylactic FVIII therapy (n=48) *The need to treat was determined by the individual or the trial physician. Individuals did not receive prophylactic factor VIII therapy. *The need to treat was determined by the individual or the trial physician. This is a before and after (intra-patient) analysis. How should I use? See the detailed Instructions for Use that comes with your for information on how to prepare and inject a dose of, and how to properly throw away (dispose of) used needles and syringes. Stop (discontinue) prophylactic use of bypassing agents the day before starting prophylaxis. You may cont What should I know about lab monitoring? may interfere with laboratory tests that measure how well your blood is clotting and may cause a false reading. Talk to your healthcare provider about how this may affect your care. What are the other possible side effects of? The most common side effects of include: redness, tenderness, warmth, or itching at the site of injection; headache; and joint pain. These are not all of the possible side effects of. Speak to your healthcare provider for medical advice about side effects. Please see Important Safety Information, including Serious Side Effects, throughout this brochure, as well as the full Prescribing Information and Medication Guide

7 CHILDREN WITH FVIII INHIBITORS (HAVEN 2) CHILDREN WITH FVIII INHIBITORS (HAVEN 2) The majority of children taking had zero treated bleeds * of children taking once weekly had ZERO TREATED BLEEDS* and an ABR of 0.3 Information based on an interim analysis of 59 children who took once weekly for a median of 30 weeks. A SMALLER GROUP OF 18 CHILDREN WAS EVALUATED BEFORE THE TRIAL BEGAN, AND THEN AGAIN ON, SO THE RESULTS COULD BE COMPARED An interim analysis of 18 children who took for at least 26 weeks and up to 63 weeks. 78 % of children who took once weekly had zero treated bleeds* 98 % fewer treated bleeds* with once weekly (ABR 0.4) vs. prior bypassing therapy (ABR 20) This is an ongoing trial. Side effects seen in children were consistent with those seen in adults and adolescents. CHILDREN WITH ZERO TREATED BLEEDS * *The need to treat was determined by the individual or the trial physician. TYPE OF BLEED (n=59) Treated bleeds* 86% All bleeds 56% Treated spontaneous bleeds 98% Treated joint bleeds 90% Treated target joint bleeds 97% *The need to treat was determined by the individual or the trial physician. All bleeds were any bleed experienced, whether treated or not. General information about the safe and effective use of. Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use for a condition for which it was not prescribed. Do not give to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about that is written for health professionals. Please see Important Safety Information, including Serious Side Effects, throughout this brochure, as well as the full Prescribing Information and Medication Guide

8 The majority of people taking had zero treated bleeds * ADULTS & ADOLESCENTS WITH FVIII INHIBITORS (HAVEN 1) A before and after analysis showed a Significant reduction in treated bleeds * compared with prior prophylactic bypassing therapy ADULTS & ADOLESCENTS WITH FVIII INHIBITORS (HAVEN 1) PEOPLE WITH ZERO TREATED BLEEDS * over at least 24 weeks COMPARED WITH PRIOR PROPHYLACTIC BYPASSING THERAPY % reduction in ABR COMPARED WITH ON-DEMAND (NO PROPHYLAXIS) BYPASSING THERAPY 20 PEOPLE WITH ZERO TREATED BLEEDS * 63 % vs. 6 % 63% of people who took once weekly had zero bleeds (n=35) vs. 6% of those who took on-demand bypassing therapy (n=18) Individuals did not receive prophylactic bypassing therapy. Annual Bleed Rate (ABR) % fewer treated bleeds* than with prior prophylactic bypassing therapy 0 COMPARED WITH PRIOR PROPHYLACTIC BYPASSING THERAPY Prior prophylactic bypassing therapy (n=24) once weekly (n=24) *The need to treat was determined by the individual or the trial physician. 71 % vs. 13 % 71% of people who took once weekly had zero bleeds (n=24) vs. 13% of those who took prior prophylactic bypassing therapy (n=24) This is a before and after (intra-patient) analysis. In this before and after comparison of prophylactic bypassing therapy and, 24 people: First took their routine prophylactic bypassing therapy and the results were measured They then switched to once weekly for at least 24 weeks and the results were measured and compared In this comparison, there were 79% fewer treated bleeds* on What is the most important information I should know about? increases the potential for your blood to clot. Carefully follow your healthcare provider s instructions regarding when to use an on-demand bypassing agent or factor VIII, and the dose and schedule to use for breakthrough bleed treatment. may cause serious side effects when used with activated prothrombin complex concentrate (apcc; FEIBA ), including thrombotic microangiopathy (TMA), and blood clots (thrombotic events). If apcc (FEIBA ) is needed, talk to your healthcare provider in case you feel you need more than 100 U/kg of apcc (FEIBA ) total. Please see Important Safety Information, including Serious Side Effects, throughout this brochure, as well as the full Prescribing Information and Medication Guide. Substantial reduction in treated bleeds* (main goal of trial) 87% fewer treated bleeds* with once weekly (ABR: 3, n=35) compared with on-demand (no prophylaxis) bypassing therapy (ABR: 23, n=18) *The need to treat was determined by the individual or the trial physician. Individuals did not receive prophylactic bypassing therapy

9 ADULTS & ADOLESCENTS WITH FVIII INHIBITORS (HAVEN 1) The opportunity to experience less pain Significantly less pain and better mobility compared with on-demand (no prophylaxis)* bypassing therapy. Painful swellings Pain with movement Joint pain gives me and my family more options. Maybe we can do something a little more than we already do, and we can plan more things ahead. Ken, patient Difficulty walking far After 25 weeks on, adults (18 and older) with factor VIII inhibitors evaluated their hemophilia-related symptoms and physical functioning using a questionnaire widely recognized by the medical community. General symptoms of pain were not measured. A patient survey explored other areas This analysis was considered exploratory, which means that it was not specifically designed to show differences. The results shown include patient responses to a survey given once a month. It may be hard to interpret the results due to the small number of participants. AVERAGE NUMBER OF EVENTS OVER 24 WEEKS prophylaxis On-demand bypassing therapy* Hospitalizations 2 (n=35) VS. 4 Missed days of school 3 (n=4) VS. 25 Missed days of work 7 (n=11) VS. 15 (n=7) (n=18) (n=4) Data based on an analysis over 24 weeks from a small follow-up survey. Numbers for missed days of school and work are based on responses only from people who were in school or working at the time of the trial, and include a limited number of respondents. *Individuals did not receive prophylactic bypassing therapy. Please see Important Safety Information, including Serious Side Effects, throughout this brochure, as well as the full Prescribing Information and Medication Guide may cause the following serious side effects when used with apcc (FEIBA ), including: Thrombotic microangiopathy (TMA). This is a condition involving blood clots and injury to small blood vessels that may cause harm to your kidneys, brain, and other organs. Get medical help right away if you have any of the following signs or symptoms during or after treatment with : confusion yellowing of skin and eyes feeling sick weakness stomach (abdomen) or back pain decreased urination swelling of arms and legs nausea or vomiting If apcc (FEIBA ) is needed, talk to your healthcare provider in case you feel you need more than 100 U/kg of apcc (FEIBA ) total.

10 How works is a therapeutic antibody a molecule created in a laboratory to treat disease. FACTOR VIIIa does not create or increase factor VIII inhibitors People with hemophilia A are missing factor VIII (8). Its job is to attach to two other molecules, activated remains active in the presence of factor VIII inhibitors factor IX (9) and factor X (10), and bring them together so blood can clot. FACTOR IXa FACTOR X Since is not derived from blood plasma, it does not contain blood viruses Platelet Cell Membrane works differently than treatments you may have used in the past. acts like a bridge, bringing activated factor IX and factor X together. This enables the clotting process to continue without needing to replace factor VIII. FACTOR IXa Platelet Cell Membrane FACTOR X may cause the following serious side effects when used with apcc (FEIBA ), including: Blood clots (thrombotic events). Blood clots may form in blood vessels in your arm, leg, lung, or head. Get medical help right away if you have any of these signs or symptoms of blood clots during or after treatment with : swelling in arms or legs fast heart rate numbness in your face pain or redness in your arms or legs cough up blood eye pain or swelling shortness of breath feel faint trouble seeing chest pain or tightness headache Please see Important Safety Information, including Serious Side Effects, throughout this brochure, as well as the full Prescribing Information and Medication Guide. If apcc (FEIBA ) is needed, talk to your healthcare provider in case you feel you need more than 100 U/kg of apcc (FEIBA ) total

11 Average level of in your blood No need to adjust dosing based on activities offers steady and consistent levels between doses In people without factor VIII inhibitors Proven bleed protection in all dosing options HAS A HALF-LIFE OF 4 WEEKS * DOSED EVERY WEEK DOSED EVERY 2 WEEKS DOSED EVERY 4 WEEKS Treatment will begin with a loading dose once weekly for 4 weeks to increase the levels of in your blood. When the loading dose is complete, you will take a maintenance dose, which helps levels in your blood remain steady. Your healthcare provider will decide how often you should take your maintenance dose, which can be once weekly, once every 2 weeks, or once every 4 weeks. 80 Loading doses Average level of in your blood 56 % ZERO TREATED BLEEDS of adults and adolescents without factor VIII inhibitors who took once weekly (n=36) had zero treated bleeds 60 % ZERO TREATED BLEEDS of adults and adolescents without factor VIII inhibitors who took once every 2 weeks (n=35) had zero treated bleeds 56 % ZERO TREATED BLEEDS of adults and adolescents with or without factor VIII inhibitors who took once every 4 weeks had zero treated bleeds 60 vs. 0% who took on-demand (no prophylaxis) FVIII therapy (n=18) vs. 0% who took on-demand (no prophylaxis) FVIII therapy (n=18) (without FVIII inhibitors, n=36; with FVIII inhibitors, n=5) once weekly (adults, adolescents, and children) every 2 weeks (adults and adolescents) every 4 weeks (adults and adolescents) In people with factor VIII inhibitors A choice of dosing schedule TIME (WEEKS) Lower levels of in blood were expected in children less than 6 months old. *After multiple subcutaneous injections, the amount of time estimated for the body to clear half of from the blood is 4 weeks. was studied once weekly in HAVEN 1 and HAVEN 2. You and your healthcare provider can choose from all 3 dosing options: once weekly, once every 2 weeks, or once every 4 weeks. Talk to your healthcare provider to choose the dosing schedule that works best for you. Once you choose a maintenance schedule, that will be your regular dosing schedule moving forward. The need to treat was determined by the individual or trial physician. Before using, tell your healthcare provider about all of your medical conditions, including if you: Individuals did not receive prophylactic factor VIII therapy. are pregnant or plan to become pregnant. It is not known if may harm your unborn baby. Females who are able to become pregnant should use birth control (contraception) during treatment with. are breastfeeding or plan to breastfeed. It is not known if passes into your breast milk. Tell your healthcare provider about all the medicines you take, including prescription medicines, over-the-counter medicines, vitamins, or herbal supplements. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine. Please see Important Safety Information, including Serious Side Effects, throughout this brochure, as well as the full Prescribing Information and Medication Guide

12 How to take The first and only subcutaneous injection for people with hemophilia A with or without factor VIII inhibitors is not an infusion into the vein. It is an injection given subcutaneously (placed under the skin). After preparation, a subcutaneous (or sub-q) injection can take less than a minute to inject. dosage strengths Use once weekly for the first 4 weeks. You will then receive a maintenance dose as prescribed by your healthcare provider. Stop (discontinue) prophylactic use of bypassing agents the day before starting You may continue prophylactic use of factor VIII for the first week of prophylaxis Speak to your healthcare provider about how to prepare and use. is available in 4 dosage strengths that are ready to use (they do not require reconstitution) Do not combine vials of different concentrations in one syringe If your healthcare provider feels it s appropriate for you, may be self-injected after proper training*. You should not inject without proper training by your healthcare provider. Your dose is based on your weight Do not mix or shake reconstitution is not required can be stored out of the refrigerator and then returned to the refrigerator Your healthcare provider will determine your dose based on your weight supplies *Self-administration is not recommended for children younger than 7 years. should not be stored out of the refrigerator for more than a total of 7 days, or stored at a temperature greater than at 86 F (30 C). Transfer needle Taking.com Syringe gauge injection needle These are the primary supplies you will need to inject : a transfer needle, a syringe, and an injection needle You can learn more about all the supplies you may need in the Instructions for Use that comes with your How should I use? See the detailed Instructions for Use that comes with your for information on how to prepare and inject a dose of, and how to properly throw away (dispose of) used needles and syringes. Stop (discontinue) prophylactic use of bypassing agents the day before starting prophylaxis. You may contkpwg RTQRJ[NCEVKE WUG QH HCEVQT 8+++ HQT VJG ƂTUV YGGM QH *'/.+$4# RTQRJ[NCZKU What should I know about lab monitoring? Please see Important Safety Information, including Serious Side Effects, throughout this brochure, as well as the full Prescribing Information and Medication Guide may interfere with laboratory tests that measure how well your blood is clotting and may cause a false reading. Talk to your healthcare provider about how this may affect your care.

13 Important Safety Information What is the most important information I should know about? increases the potential for your blood to clot. Carefully follow your healthcare provider s instructions regarding when to use an on-demand bypassing agent or factor VIII, and the dose and schedule to use for breakthrough bleed treatment. may cause the following serious side effects when used with activated prothrombin complex concentrate (apcc; FEIBA ), including: Thrombotic microangiopathy (TMA). This is a condition involving blood clots and injury to small blood vessels that may cause harm to your kidneys, brain, and other organs. Get medical help right away if you have any of the following signs or symptoms during or after treatment with : confusion yellowing of skin and eyes feeling sick weakness stomach (abdomen) or back pain decreased urination swelling of arms and legs nausea or vomiting Blood clots (thrombotic events). Blood clots may form in blood vessels in your arm, leg, lung, or head. Get medical help right away if you have any of these signs or symptoms of blood clots during or after treatment with : swelling in arms or legs fast heart rate numbness in your face pain or redness in your arms or legs cough up blood eye pain or swelling shortness of breath feel faint trouble seeing chest pain or tightness headache If apcc (FEIBA ) is needed, talk to your healthcare provider in case you feel you need more than 100 U/kg of apcc (FEIBA ) total. Before using, tell your healthcare provider about all of your medical conditions, including if you: are pregnant or plan to become pregnant. It is not known if may harm your unborn baby. Females who are able to become pregnant should use birth control (contraception) during treatment with. How should I use? See the detailed Instructions for Use that comes with your for information on how to prepare and inject a dose of, and how to properly throw away (dispose of) used needles and syringes. Stop (discontinue) prophylactic use of bypassing agents the day before starting prophylaxis. What should I know about lab monitoring? may interfere with laboratory tests that measure how well your blood is clotting and may cause a false reading. Talk to your healthcare provider about how this may affect your care. The most common side effects of include: redness, tenderness, warmth, or itching at the site of injection; headache; and joint pain. These are not all of the possible side effects of. Speak to your healthcare provider for medical advice about side effects. Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use for a condition for which it was not prescribed. Do not give to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about that is written for health professionals. You may report side effects to the FDA at (800) FDA-1088 or You may also report side effects to Genentech at (888) are breastfeeding or plan to breastfeed. It is not known if passes into your breast milk. Tell your healthcare provider about all the medicines you take, including prescription medicines, over-the-counter medicines, vitamins, or herbal supplements. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine. Please see Important Safety Information, including Serious Side Effects, throughout this brochure, as well as the full Prescribing Information and Medication Guide. References: 1. Oldenburg J, Mahlangu JN, Kim B, et al. Supplement to: Emicizumab prophylaxis in hemophilia A with inhibitors. N Engl J Med. 2017;377: Genentech Data on File. 3. Young G, Sidonio R, Liesner R, et al. HAVEN 2: Efficacy, Safety, and Pharmacokinetics of Once-Weekly Prophylactic Emicizumab (ACE910) in Pediatric Patients (<12 Years) with Hemophilia A with Inhibitors: Interim Analysis of Single-Arm, Multicenter, Open-label, Phase 3 Study. Oral presentation at: American Society of Hematology Annual Meeting; December 9-12, 2017; Atlanta, GA. 4. Oldenburg J, Mahlangu JN, Kim B, et al. Emicizumab prophylaxis in hemophilia A with inhibitors. N Engl J Med. 2017;377: National Cancer Institute. NCI Dictionaries. Bethesda, MD: National Institutes of Health (US); Bolton-Maggs PH, Pasi KJ, et al. Haemophilias A and B. Lancet. 2003;361(9371): Carr M, Torella B. Emerging and future therapies for hemophilia. J Blood Med. 2015;6: Doyle GR, McCutcheon JA. Clinical Procedures for Safer Patient Care. Victoria, BC: BCcampus; Accessed May 22,

14 Important things to know is not a cure for hemophilia should be refrigerated, but it can be kept at room temperature for up to a total of 7 days is for routine prophylactic use only and should not be used as on-demand therapy. You may have a bleed while taking. Talk to your healthcare provider about how to treat any bleeds that may occur. Develop a plan to store your medication in appropriate conditions. may cause serious side effects when used with apcc (FEIBA ) Anti-drug antibodies (ADAs) can occur when taking increases the potential for your blood to clot. Discontinue prophylactic use of bypassing agents the day before starting prophylaxis. Carefully follow your healthcare provider s instructions regarding when to use an on-demand bypassing agent, and the dose and schedule you should use. If the bypassing therapy apcc (FEIBA ) is needed, talk to your healthcare provider in case you feel you need more than 100 U/kg of apcc (FEIBA ) total. ADAs are our body s natural reaction to molecules it detects as foreign in this case,. They are not inhibitors and do not impact factor VIII replacement therapy or other medicines. Neutralizing ADAs are anti-drug antibodies that have the potential to make a medicine ineffective. The incidence of ADAs in clinical trials was 3.5%, with <1% ADAs with neutralizing potential. There was no apparent impact of the presence of ADAs on safety. The number of patients with -related ADAs may be under-reported due to the sensitivity of the test used to detect them. Be sure to speak with your healthcare provider if you have any questions about ADAs. may interfere with laboratory tests that measure how well your blood is clotting, and may cause a false reading Day 1 Key Considerations NI v19f_cover_mech.pdf 1 10/3/18 08:54 does not create factor VIII inhibitors Before beginning, speak to your healthcare provider to discuss how this may affect your care. You may need to share this information with other healthcare providers, such as dentists, surgeons, or ER staff, prior to a blood test, medical procedure, or surgery. FVIII is a therapeutic antibody, not a factor VIII replacement therapy. Because it is not factor VIII, it does not create factor VIII inhibitors. is also not impacted by existing factor VIII inhibitors. Please see Important Safety Information, including Serious Side Effects, throughout this brochure, as well as the full Prescribing Information and Medication Guide

15 Support resources Meet your Clinical Educator: a resource for you and your family At Genentech, we aspire to be a partner in the community. Our Hemophilia Community Clinical Educators, called CEs, are a team of inspired educators who are passionate about the hemophilia community. Each member of the team has a nursing degree, and all are committed to serving as an educational resource for people with hemophilia A and their families. Your CE can help: Call (866) or (866) Our comprehensive resource hub, Connects, helps you get the information you need about. We can help you: Get answers to your questions quickly and efficiently Answer questions about approved Genentech products (including injection education following training by your healthcare provider) Provide information about educational programs and events Be connected to your local Clinical Educator Learn about our Co-Pay Program that may help you with the out-of-pocket costs of if you are eligible Connect you to resources providing access to Genentech medicines for eligible patients CEs do not provide medical advice, as that should always be a conversation between you and your healthcare provider. Find your CE at.com/ce or (866). Understand your health insurance coverage for Access Solutions may be able to help you understand how to get the you need, even if you can t pay for it. Find out more in the Access Solutions brochure in the Welcome Kit, or by visiting.com. We re here to help, in English and Spanish, 9am to 8pm ET (6am to 5pm PT), Monday through Friday. Sign up at.com to receive news updates and treatment tips. Please see Important Safety Information, including Serious Side Effects, throughout this brochure, as well as the full Prescribing Information and Medication Guide

16 PI POCKET Conversations with your healthcare team Notes If you are thinking about the next step for treatment of your hemophilia A, it may be the right time to talk with your healthcare provider about. In addition to your own questions, it may be helpful to discuss the following topics. Is right for me? What are the risks and benefits of? How will I manage a bleed while taking? What are the potential side effects? C M Y How do I prepare for emergency situations? CM MY CY CMY K Bring this brochure to your next appointment with your healthcare provider, and visit.com or call us at (866) or (866) for more information. Please see Important Safety Information, including Serious Side Effects, throughout this brochure, as well as the full Prescribing Information and Medication Guide

17 FOR P ven bleed Proven protection bleed protection for people for with people hemophilia with hemophilia A A or without or factor without VIII factor inhibitors VIII inhibitors GO G PROVEN EFFECTIVE TO REDUCE BLEEDS REQUIRING TREATMENT* COMPARED WITH NO PROPHYLAXIS (MAIN GOAL OF 2 TRIALS) IN 2 INTRA-PATIENT ANALYSES, PEOPLE HAD A SIGNIFICANT REDUCTION IN TREATED BLEEDS * COMPARED WITH BOTH PRIOR PROPHYLAXIS FVIII AND BYPASSING THERAPY THE MAJORITY OF PEOPLE HAD ZERO BLEEDS REQUIRING TREATMENT * Based on information from 2 trials: adults and adolescents with factor VIII inhibitors adults and adolescents without factor VIII inhibitors Safety evaluated in the largest clinical trial program in hemophilia A with and without factor VIII inhibitors First and only prophylactic is a therapeutic is a therapeutic subcutaneous injection antibody that works antibody differently that works differently with 3 dosing options than other treatments, than other and treatments, and maintains consistent maintains drug consistent levels drug levels ed to treat *The was need determined to treat by was the determined individual or by the the trial individual physician. or the trial physician. is the most What important is the most information important I should information know I about should? know about? IBRA increases the potential increases for the your potential blood for to clot. your Carefully blood to clot. follow Carefully your healthcare follow your provider s healthcare provider s What ctions regarding instructions when regarding to use an when on-demand to use an bypassing on-demand agent bypassing or factor agent VIII, and or factor the dose VIII, and and the dose and HEML ule to use schedule for breakthrough to use for breakthrough bleed treatment. bleed treatment. may cause serious may side cause effects serious when side used effects when used episod ctivated with prothrombin activated complex prothrombin concentrate complex (apcc; concentrate FEIBA ), (apcc; including FEIBA thrombotic ), including microangiopathy thrombotic microangiopathy, and blood What (TMA), clots and (thrombotic blood clots events). (thrombotic If apcc events). (FEIBA If ) apcc is needed, (FEIBA talk ) is to needed, your healthcare talk to your provider healthcare in provider in ou feel you case need you more feel you than need 100 more U/kg than of apcc 100 (FEIBA U/kg of ) apcc total. (FEIBA ) total. HEML see Important instru Please Safety see Important Information, Safety including Information, Serious including Side Effects, Serious throughout Side Effects, this throughout brochure, as this well brochure, as as well as MLIBRA full sched the Prescribing Information full Prescribing and Information Medication and Guide. Medication Guide. with a (TMA case y FPO FPO FPO FPO enentech USA, 2018 Inc. All Genentech rights reserved. USA, Inc. EMI/091117/0114(1) All rights reserved. EMI/091117/0114(1) A is a registered trademark is a of registered Chugai Pharmaceutical trademark of Chugai Co., Ltd., Pharmaceutical Tokyo, Japan. Co., Ltd., Tokyo, Japan. LIBRA logo is The a trademark of logo Chugai is a Pharmaceutical trademark of Chugai Co., Ltd., Pharmaceutical Tokyo, Japan. Co., Ltd., Tokyo, Japan. ntech logo is The a registered Genentech trademark logo is a of registered Genentech, trademark Inc. of Genentech, Inc. trademarks are All the other property trademarks of their are respective the property owners. of their respective owners. Disc Please the HE

18 HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use safely and effectively. See full prescribing information for. (emicizumab-kxwh) injection, for subcutaneous use Initial U.S. Approval: 2017 WARNING: THROMBOTIC MICROANGIOPATHY and THROMBOEMBOLISM See full prescribing information for complete boxed warning. Cases of thrombotic microangiopathy and thrombotic events were reported when on average a cumulative amount of >100 U/kg/24 hours of activated prothrombin complex concentrate (apcc) was administered for 24 hours or more to patients receiving prophylaxis. Monitor for the development of thrombotic microangiopathy and thrombotic events if apcc is administered. Discontinue apcc and suspend dosing of if symptoms occur. RECENT MAJOR CHANGES Indications and Usage (1) 10/2018 Dosage and Administration (2.1) 10/2018 INDICATIONS AND USAGE is a bispecific factor IXa- and factor X-directed antibody indicated for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients ages newborn and older with hemophilia A (congenital factor VIII deficiency) with or without factor VIII inhibitors. (1) DOSAGE AND ADMINISTRATION Recommended loading dose is 3 mg/kg by subcutaneous injection once weekly for the first 4 weeks, followed by a maintenance dose of: 1.5 mg/kg once every week, or 3 mg/kg once every two weeks, or 6 mg/kg once every four weeks. (2.1) See Full Prescribing Information for important preparation and administration instructions. (2.2) DOSAGE FORMS AND STRENGTHS Injection: 30 mg/ml in a single-dose vial (3) 60 mg/0.4 ml in a single-dose vial (3) 105 mg/0.7 ml in a single-dose vial (3) 150 mg/ml in a single-dose vial (3) CONTRAINDICATIONS None (4) WARNINGS AND PRECAUTIONS Laboratory Coagulation Test Interference: interferes with activated clotting time (ACT), activated partial thromboplastin time (aptt), and coagulation laboratory tests based on aptt, including onestage aptt-based single-factor assays, aptt-based Activated Protein C Resistance (APC-R), and Bethesda assays (clotting-based) for factor VIII (FVIII) inhibitor titers. Intrinsic pathway clotting-based laboratory tests should not be used. (5.3, 7.2) ADVERSE REACTIONS Most common adverse reactions (incidence 10%) are injection site reactions, headache, and arthralgia. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Genentech at or FDA at FDA-1088 or See 17 for PATIENT COUNSELING INFORMATION and Medication Guide. Revised: 10/2018 FULL PRESCRIBING INFORMATION: CONTENTS* WARNING: THROMBOTIC MICROANGIOPATHY and THROMBOEMBOLISM 1 INDICATIONS AND USAGE 2 DOSAGE AND ADMINISTRATION 2.1 Recommended Dosage 2.2 Preparation and Administration 3 DOSAGE FORMS AND STRENGTHS 4 CONTRAINDICATIONS 5 WARNINGS AND PRECAUTIONS 5.1 Thrombotic Microangiopathy Associated with and apcc 5.2 Thromboembolism Associated with and apcc 5.3 Laboratory Coagulation Test Interference 6 ADVERSE REACTIONS 6.1 Clinical Trials Experience 6.2 Immunogenicity 7 DRUG INTERACTIONS 7.1 Hypercoagulability with Concomitant Use of apcc 7.2 Drug-Laboratory Test Interactions 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy 8.2 Lactation 8.3 Females and Males of Reproductive Potential 8.4 Pediatric Use 8.5 Geriatric Use 11 DESCRIPTION 12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action 12.3 Pharmacokinetics 13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility 14 CLINICAL STUDIES 14.1 Hemophilia A without FVIII Inhibitors 14.2 Hemophilia A with FVIII Inhibitors 16 HOW SUPPLIED/STORAGE AND HANDLING 17 PATIENT COUNSELING INFORMATION * Sections or subsections omitted from the full prescribing information are not listed.

19 FULL PRESCRIBING INFORMATION WARNING: THROMBOTIC MICROANGIOPATHY AND THROMBOEMBOLISM Cases of thrombotic microangiopathy and thrombotic events were reported when on average a cumulative amount of >100 U/kg/24 hours of activated prothrombin complex concentrate was administered for 24 hours or more to patients receiving prophylaxis. Monitor for the development of thrombotic microangiopathy and thrombotic events if apcc is administered. Discontinue apcc and suspend dosing of if symptoms occur. 1 INDICATIONS AND USAGE is indicated for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients ages newborn and older with hemophilia A (congenital factor VIII deficiency) with or without factor VIII inhibitors. 2 DOSAGE AND ADMINISTRATION 2.1 Recommended Dosage For subcutaneous use only. The recommended loading dose is 3 mg/kg by subcutaneous injection once weekly for the first 4 weeks, followed by a maintenance dose of: 1.5 mg/kg once every week, or 3 mg/kg once every two weeks, or 6 mg/kg once every four weeks. The selection of a maintenance dose should be based on healthcare provider preference with consideration of regimens that may increase patient adherence. Discontinue the prophylactic use of bypassing agents the day before starting prophylaxis. The prophylactic use of factor VIII (FVIII) products may be continued during the first week of prophylaxis. Missed Dose If a dose of is missed administer as soon as possible and then resume usual dosing schedule. Do not administer two doses on the same day to make up for a missed dose. 2.2 Preparation and Administration is intended for use under the guidance of a healthcare provider. After proper training in subcutaneous injection technique, a patient may self-inject, or the patient s caregiver may administer, if a healthcare provider determines that it is appropriate. Self-administration is not recommended for children less than 7 years of age. The Instructions for Use contains more detailed instructions on the preparation and administration of [see Instructions for Use]. Visually inspect for particulate matter and discoloration before administration. for subcutaneous administration is a colorless to slightly yellow solution. Do not use if particulate matter is visible or product is discolored. A syringe, a transfer needle and an injection needle are needed to withdraw solution from the vial and inject it subcutaneously. Refer to the Instructions for Use for handling instructions when combining vials. Do not combine vials of different concentrations in a single injection.

20 Administer doses of up to 1 ml with a 1 ml syringe. A 1 ml syringe fulfilling the following criteria may be used: Transparent polypropylene or polycarbonate syringe with Luer-Lock tip, graduation 0.01 ml, sterile, for injection only, single-use, latex-free and nonpyrogenic, commercially available in the US. Administer doses of greater than 1 ml and up to 2 ml with a 2 ml or 3 ml syringe. A 2 ml or 3 ml syringe fulfilling the following criteria may be used: Transparent polypropylene or polycarbonate syringe with Luer-Lock tip, graduation 0.1 ml, sterile, for injection only, single-use, latex-free, and non-pyrogenic, commercially available in the US. A transfer needle fulfilling the following criteria may be used: Stainless steel needle with Luer-Lock connection, sterile, 18 gauge, length 1 to 1½ inch, single bevel or semi-blunted tip, single-use, latex-free, and non-pyrogenic, commercially available in the US. An injection needle fulfilling the following criteria may be used: Stainless steel with Luer-Lock connection, sterile, 26 gauge (acceptable range: gauge), length preferably 3 / 8 inch or maximal length ½ inch, single-use, latex-free and non-pyrogenic, including needle safety feature, commercially available in the US. Administer each injection at a different anatomic location (upper outer arms, thighs, or any quadrant of abdomen) than the previous injection. An injection should never be given into moles, scars, or areas where the skin is tender, bruised, red, hard, or not intact. Administration of in the upper outer arm should only be performed by a caregiver or healthcare provider. Discard any unused remaining in the single-dose vial. 3 DOSAGE FORMS AND STRENGTHS is available as a colorless to slightly yellow solution in single-dose vials. Injection: 30 mg/ml 60 mg/0.4 ml 105 mg/0.7 ml 150 mg/ml 4 CONTRAINDICATIONS None. 5 WARNINGS AND PRECAUTIONS 5.1 Thrombotic Microangiopathy Associated with and apcc Cases of thrombotic microangiopathy (TMA) were reported from clinical trials when on average a cumulative amount of >100 U/kg/24 hours of activated prothrombin complex concentrate (apcc) was administered for 24 hours or more to patients receiving prophylaxis. In clinical trials, thrombotic microangiopathy was reported in 0.8% of patients (3/391) and in 8.1% of patients (3/37) who received at least one dose of apcc. Patients presented with thrombocytopenia, microangiopathic hemolytic anemia, and acute kidney injury, without severe deficiencies in ADAMTS13 activity. Evidence of improvement was seen within one week following discontinuation of apcc. One patient resumed following resolution of TMA. Consider the benefits and risks if apcc must be used in a patient receiving prophylaxis. Monitor for the development of TMA when administering apcc. Immediately discontinue apcc and interrupt prophylaxis if clinical symptoms and/or laboratory findings consistent with TMA occur, and manage as clinically indicated. Consider the benefits

21 and risks of resuming prophylaxis following complete resolution of TMA on a case-by-case basis. 5.2 Thromboembolism Associated with and apcc Thrombotic events were reported from clinical trials when on average a cumulative amount of >100 U/kg/24 hours of apcc was administered for 24 hours or more to patients receiving prophylaxis. In clinical trials, thrombotic events were reported in 0.5% of patients (2/391) and in 5.4% of patients (2/37) who received at least one dose of apcc. No thrombotic event required anticoagulation therapy. Evidence of improvement or resolution was seen within one month following discontinuation of apcc. One patient resumed following resolution of thrombotic event. Consider the benefits and risks if apcc must be used in a patient receiving prophylaxis. Monitor for the development of thromboembolism when administering apcc. Immediately discontinue apcc and interrupt prophylaxis if clinical symptoms, imaging, or laboratory findings consistent with thromboembolism occur, and manage as clinically indicated. Consider the benefits and risks of resuming prophylaxis following complete resolution of thrombotic events on a case-by-case basis. 5.3 Laboratory Coagulation Test Interference affects intrinsic pathway clotting-based laboratory tests, including activated clotting time (ACT), activated partial thromboplastin time (aptt), and all assays based on aptt, such as one-stage factor VIII (FVIII) activity (Table 1). Therefore, intrinsic pathway clottingbased laboratory test results in patients treated with should not be used to monitor activity, determine dosing for factor replacement or anti-coagulation, or measure FVIII inhibitor titers [see Drug Interactions (7.2)]. Laboratory tests affected and unaffected by are shown in Table 1. Table 1 Coagulation Test Results Affected and Unaffected by Results Affected by Activated partial thromboplastin time (aptt) Bethesda assays (clotting-based) for FVIII inhibitor titers One-stage, aptt-based, single-factor assays aptt-based Activated Protein C Resistance (APC-R) Activated clotting time (ACT) Results Unaffected by Bethesda assays (bovine chromogenic) for FVIII inhibitor titers Thrombin time (TT) One-stage, prothrombin time (PT)-based, singlefactor assays Chromogenic-based single-factor assays other than FVIII* Immuno-based assays (i.e., ELISA, turbidimetric methods) Genetic tests of coagulation factors (e.g., Factor V Leiden, Prothrombin 20210) *For important considerations regarding FVIII chromogenic activity assays, see Drug Interactions (7.2). 6 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in the labeling: Thrombotic Microangiopathy Associated with and apcc [see Warnings and Precautions (5.1)] Thromboembolism Associated with and apcc [see Warnings and Precautions (5.2)]