Hemlibra® (EMICIZUMAB-KXWH)

About HEMLIBRA

HEMLIBRA® (emicizumab-kxwh) is approved by the FDA as a prophylactic medicine used to prevent or reduce the frequency of bleeding episodes in adults and children with hemophilia A with factor VIII inhibitors.1 It is given once a week subcutaneously (under the skin).

FIRST new FDA-approved medicine to treat hemophilia A with inhibitors in nearly 20 years
FIRST bispecific monoclonal antibody approved to treat hemophilia A with inhibitors
• Bridges factors IXa and X in the blood clotting cascade
ONLY treatment option for hemophilia A with inhibitors that can be self-administered once weekly by injection subcutaneously
• Provided improvement in Physical Health Score of the Haemophilia-specific Quality of Life (Haem-A-QoL) questionnaire

What is the most important information to know about HEMLIBRA?
HEMLIBRA may cause serious side effects when used with aPCC (FEIBA®), including thrombotic microangiopathy (TMA) and blood clots (thrombotic events). 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 HEMLIBRA prophylaxis.

About Hemophilia A With Inhibitors

Hemophilia A is a rare, genetic blood disease where missing or faulty blood clotting factor VIII prevents blood from clotting normally. This can cause frequent bleeding, especially into the joints or muscles.1 These bleeds often cause pain2 and can lead to chronic swelling, deformity, reduced mobility and long-term joint damage.3 Factor VIII replacement therapy is a standard treatment for people with hemophilia A, but in some people, their immune systems recognize this as a foreign substance and generate antibodies to attack it. These antibodies are called inhibitors.2

About Hemophilia A

Hemophilia occurs more frequently in males than females.2

  • NEARLY 20,000

    PEOPLE IN THE U.S. HAVE HEMOPHILIA; HEMOPHILIA A IS THE MOST COMMON TYPE2

  • ABOUT 50-60%

    OF PEOPLE WITH HEMOPHILIA A HAVE A SEVERE FORM OF THE DISORDER2

About Hemophilia A With Inhibitors

  • ABOUT 20-30%

    OF PEOPLE WITH HEMOPHILIA A CAN DEVELOP INHIBITORS THAT BIND TO AND BLOCK THE EFFICACY OF FACTOR VIII REPLACEMENT THERAPY4,5

Inhibitors make it difficult, if not impossible in some people, to obtain a level of factor VIII sufficient to control bleeding.6,7,8 Management of bleeding in people with inhibitors can be a major challenge.

How HEMLIBRA May Work (Proposed Mechanism of Action)1

Clotting factors activate each other to form a blood clot, or coagulate. These processes are known as the coagulation cascade. People with hemophilia A do not have enough functional natural protein factor VIII.

HEMLIBRA is a bispecific factor IXa- and factor X-directed antibody designed to activate the natural coagulation cascade and restore the blood clotting process for hemophilia A.

By replacing the function of natural activated factor VIII, HEMLIBRA promotes blood clotting.

HEMLIBRA is a different type of molecule than activated factor VIII, and is therefore not expected to induce inhibitors or be affected by inhibitors.

HEMLIBRA has a long half-life of approximately 4 weeks, which is related to the amount of time the medicine remains active in the body.

HEMLIBRA Efficacy1

The FDA approval of HEMLIBRA is based on positive results from a Phase III clinical study in adolescents and adults (HAVEN 1), and interim results from a pivotal clinical study in children (HAVEN 2).

In the HAVEN 1 study of 109 adolescents and adults (12 years and older) with hemophilia A with inhibitors, once weekly preventative (prophylaxis) administration of HEMLIBRA substantially reduced treated bleeds compared to on-demand (episodic) or preventative use of bypassing agents (BPAs):

Primary Endpoint

Secondary Endpoints

Improvements in bleed rate with HEMLIBRA prophylaxis compared to no prophylaxis were consistent across all secondary bleed endpoints, including an:

HEMLIBRA Efficacy1

The HAVEN 1 study is the first to be designed to directly compare the effects of different prophylaxis therapies in the same person with hemophilia A with inhibitors. This first-of-its-kind intra-patient analysis showed a statistically significant:

An improvement in Physical Health Score of the Haem-A-QoL questionnaire was observed with HEMLIBRA prophylaxis compared to no prophylaxis. This was measured at 25 weeks and evaluated hemophilia-related symptoms and physical function including:

HAVEN 2 is a single-arm, multicenter, open-label, clinical study in children younger than 12 years of age with hemophilia A with inhibitors. In an interim efficacy analysis, annualized bleed rate and percent of subjects with zero bleeds were calculated for 23 children who received once weekly HEMLIBRA prophylaxis. After a median observation time of 38.1 weeks, this interim analysis showed that:

An intra-patient analysis in the HAVEN 2 study was also conducted to compare the effects of different therapies in the same child (n=13). In this analysis, HEMLIBRA prophylaxis resulted in a:

HEMLIBRA Pooled Safety1

In pooled results of 189 patients in HAVEN 1, HAVEN 2 and dose-finding trial, the most common adverse reactions (≥10%) observed in people treated with HEMLIBRA were injection site reactions, headache and joint pain (arthralgia).

What it Treats

What is HEMLIBRA?

HEMLIBRA is a prescription medicine used for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adults and children with hemophilia A with factor VIII inhibitors.

Important Safety Information

What is the most important information I should know about HEMLIBRA?

HEMLIBRA increases the potential for your blood to clot. Discontinue prophylactic use of bypassing agents the day before starting HEMLIBRA 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. HEMLIBRA 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 HEMLIBRA:
    • confusion
    • weakness
    • swelling of arms and legs
    • yellowing of skin and eyes
    • stomach (abdomen) or back pain
    • nausea or vomiting
    • feeling sick
    • decreased urination
  • 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 HEMLIBRA:
    • swelling in arms or legs
    • pain or redness in your arms or legs
    • shortness of breath
    • chest pain or tightness
    • fast heart rate
    • cough up blood
    • feel faint
    • headache
    • numbness in your face
    • eye pain or swelling
    • trouble seeing

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 HEMLIBRA, 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 HEMLIBRA may harm your unborn baby. Females who are able to become pregnant should use birth control (contraception) during treatment with HEMLIBRA.
  • are breastfeeding or plan to breastfeed. It is not known if HEMLIBRA 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.

How should I use HEMLIBRA?

See the detailed “Instructions for Use” that comes with your HEMLIBRA for information on how to prepare and inject a dose of HEMLIBRA, and how to properly throw away (dispose of) used needles and syringes.

HEMLIBRA 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 HEMLIBRA?

The most common side effects of HEMLIBRA 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 HEMLIBRA. Call your doctor for medical advice about side effects.

General information about the safe and effective use of HEMLIBRA.

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use HEMLIBRA for a condition for which it was not prescribed. Do not give HEMLIBRA 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 HEMLIBRA that is written for health professionals.

You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at (888) 835-2555.

Please see the HEMLIBRA full Prescribing Information and Medication Guide for more important safety information including Serious Side Effects.

HEMLIBRA is a registered trademark of Chugai Pharmaceutical Co., Ltd., Tokyo, Japan.

The HEMLIBRA logo is a trademark of Chugai Pharmaceutical Co., Ltd., Tokyo, Japan.

The Genentech logo is a registered trademark of Genentech, Inc.

References

  1. HEMLIBRA (emicizumab-kxwh) Prescribing Information. Genentech, Inc. 2017.
  2. Centers of Disease Control and Prevention. Hemophilia Facts. http://www.cdc.gov/ncbddd/hemophilia/facts.html. 2014. Accessed June 30, 2016.
  3. National Hemophilia Foundation. Types of Bleeds. https://www.hemophilia.org/Bleeding-Disorders/Types-of-Bleeds. Accessed July 10, 2017.
  4. NIH. How is Hemophilia Treated? http://www.nhlbi.nih.gov/health/health-topics/topics/hemophilia/treatment. Accessed July 8, 2016.
  5. Centers of Disease Control and Prevention. Inhibitors. https://www.cdc.gov/ncbddd/hemophilia/inhibitors.html. 2014. Accessed June 30, 2016.
  6. Whelan SF, et al. Distinct Characteristics of Antibody Responses Against Factor VIII in Healthy Individuals and in Different Cohorts of Hemophilia A Patients. Blood 2013; 121:1039–48.
  7. National Hemophilia Foundation. What is an Inhibitor? https://www.hemophilia.org/Bleeding-Disorders/Inhibitors-Other-Complications/Inhibitors-for-Consumers/What-is-an-Inhibitor. Accessed August 31, 2017.
  8. American Society of Hematology Blood Journal. F8 gene Mutation Type and Inhibitor Development in Patients with Severe Hemophilia A: Systematic Review and Meta-Analysis. http://www.bloodjournal.org/content/119/12/2922.long?sso-checked=true. Accessed August 31, 2017.