Why HEMLIBRA?

HEMLIBRA is the #1 prescribed prophylaxis for all people with hemophilia A*1

*According to IQVIA claims data from various insurance plan types from April 2020 - May 2021 (refreshed August 2021) and accounts for usage in prophylaxis settings in the US.

Hundreds studied.
Thousands treated.

HEMLIBRA has been studied with clinical trial experience of ~700 patients with hemophilia A, and is used by 11,500+ worldwide, including 5700 patients in the US†‡2-4

Flexible dosing options

HEMLIBRA gives you the freedom to choose a dosing option that works best for your patient. After 4 weeks of a weekly loading dose, patients can take maintenance doses every week, every 2 weeks, or every 4 weeks5

A half-life that is measured in weeks—not hours

The unique 4-week half-life of HEMLIBRA offers consistent and sustained therapeutic drug levels, regardless of age or dosing option§5

Clinical trial experience started in 2013 in the Phase 1/2 study.
Number of people with hemophilia A treated with HEMLIBRA as of August 2021.
§Following multiple subcutaneous injections in patients with hemophilia A, the mean elimination apparent half-life of HEMLIBRA was 26.9±9.1 days.

Why would I expand my use of HEMLIBRA beyond the obvious cases?

Featuring Dr. Tami Singleton, Dr. Sanjay Ahuja, nurse Courtney Carr, and a patient with hemophilia A, Louis C.

VO:

HEMLIBRA 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 with or without factor VIII inhibitors. HEMLIBRA has a Boxed Warning for thrombotic microangiopathy and thromboembolism. Cases of thrombotic microangiopathy and thrombotic events were reported when on average a cumulative amount of over 100 units per kilogram per day of activated prothrombin complex concentrate, aPCC, was administered for 24 hours or more to patients receiving HEMLIBRA prophylaxis.

Dr. Tami Singleton:

Since HEMLIBRA was approved in 2017, thousands of patients have switched, but not all healthcare professionals are onboard. I'm Dr. Tami Singleton, an HTC director in Southeast Louisiana. With the help of my colleagues and real people living with hemophilia A, we're going to answer some of the tough questions about HEMLIBRA.

ON SCREEN:

Why would I expand my use of HEMLIBRA beyond the obvious cases?

Dr. Tami Singleton:

So, today's question is one I've heard before. Factor Replacement Therapy is tried and true. So, why wouldn't I continue to use that in most of my patients with hemophilia A and just reserve HEMLIBRA for those specific types of patients where Factor isn't working well. Usually that's someone with venous access issues or someone with Factor VIII inhibitors or someone who's continuing to have a significant number of treated bleeds.

ON SCREEN:

  • Venous access issues
  • Factor VIII Inhibitors
  • Significant number of bleeds needing treatment

Dr. Tami Singleton:

I sent this question out to treaters in the community and people with hemophilia to see what they thought. I'm going to sit down with them and learn more about how and why they expanded the use to more types of patients with hemophilia A.

Sanjay, for me, you absolutely need no introduction. In terms of HEMLIBRA, let's chat a little bit about your opinion, at least initially, if you can think back to that.

ON SCREEN:

Initial Opinions

Sanjay Ahuja:

We were a little bit hesitant to switch everybody who had hemophilia without inhibitors to HEMLIBRA. The patients that we thought were most ideal to start with were patients that had difficulty in venous access.

Courtney Carr:

And then I was a little nervous about using it for all hemophilia patients, just because I was a little nervous about how they would feel with switching to a new medication.

Louis:

When I had first heard the word HEMLIBRA and I heard about subcutaneous injections, I was a little freaked out.

Dr. Tami Singleton:

What made you kind of pull that trigger to start HEMLIBRA on one of the patients that may have been considered sort of non-traditional for you?

ON SCREEN:

Starting to expand use

Sanjay Ahuja:

There was initial concern with the TMA, the thrombotic microangiopathy and the thrombosis that were worrisome to some physicians including me. But as our experience grew, we understood that TMA was only because of a certain association with the PCC, the prothrombin complex concentrates that were given in addition to HEMLIBRA at a certain dose.

Dr. Tami Singleton:

Monitor for the development of thrombotic microangiopathy and thrombotic events. If an aPCC is administered, discontinue the aPCC and suspend dosing of HEMLIBRA if symptoms occur.

ON SCREEN:

Important Safety Information

Boxed 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 (aPCC) was administered for 24 hours or more to patients receiving HEMLIBRA prophylaxis. Monitor for the development of thrombotic microangiopathy and thrombotic events if aPCC is administered. Discontinue aPCC and suspend dosing of HEMLIBRA if symptoms occur.

Sanjay Ahuja:

Our experience grew with other patients, so we became more comfortable. We expanded our use of HEMLIBRA to other patients with hemophilia A without inhibitors. One particular example that I can think of is a family that had two boys, siblings, with hemophilia A, that I offered the therapy to. They were treating bleeds off and on throughout the year intravenously through a peripheral vein and I offered the therapy to them. However, we were able to move to once every four weeks therapy with HEMLIBRA. And that change was amazing for the boys, both of them. They were no longer trying to find veins in their busy school schedules. So they were, not only they but their mom was also very happy with the change.

ON SCREEN:

After the 4 weekly loading doses, HEMLIBRA can be taken once a week, once every 2 weeks, or once every 4 weeks. If a dose of HEMLIBRA is missed, administer as soon as possible and then resume usual dosing schedule. Do not administer 2 doses on the same day to make up for a missed dose.

Courtney Carr:

With all the patients that I have on HEMLIBRA, even the first five that came back, hearing their improvement, that really sealed it for me.

Dr. Tami Singleton:

Let me jump in here and give you a quick rundown of the pivotal trial data. In HAVEN 3 and HAVEN 4, most patients taking HEMLIBRA had zero bleeds requiring treatment, regardless of whether HEMLIBRA was taken once a week, once every two weeks or once every four weeks. HAVEN 3 included adults and adolescents without inhibitors and HAVEN 4 included adults and adolescents with or without inhibitors.

ON SCREEN:

Primary Endpoint

The majority of patients on HEMLIBRA had zero treated bleeds

  • Every week (adults and adolescents without FVIII inhibitors): 56% vs. 0%
  • Every 2 weeks (adults and adolescents without FVIII inhibitors): 60% vs. 0%
  • Every 4 weeks (adults and adolescents with or without FVIII inhibitors): 56% vs. 0%

*The median efficacy period was up to 31 weeks

The median efficacy period was 26 weeks

Courtney Carr:

I've gotten more comfortable prescribing to different age groups, different severities, as well as male and female patients. I think it's just been a total transformation for me as I've done more research about the medication.

ON SCREEN:

HEMLIBRA 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 with or without factor VIII inhibitors.

Dr. Tami Singleton:

So, you're a young guy, you're in your twenties, no history of inhibitors. So, some people may not consider you a very obvious candidate for HEMLIBRA. How did you come to learn about it?

ON SCREEN:

Seeing HEMLIBRA in Action

Louis:

I'm a counselor at a camp for kids with bleeding disorders and one of my campers was using this medicine and I was like, wow, you know, looks like a sub-Q injection. I have never seen anything like that for hemophilia treatment ever. So I was kind of just blown away because he was like, "Yeah, I do it once a week." And I was like, "Once a week?" And it's not even taking him that long. You know, I went—immediately I got back from camp and I went to go speak to my doctor and I was like, "Can we possibly talk about this?" And that's where the conversation took off.

ON SCREEN:

After proper training in subcutaneous technique, a patient may self-inject, or the patient’s caregiver may administer HEMLIBRA, if a healthcare provider determines that it is appropriate. Self-administration is not recommended for children less than 7 years of age.

Dr. Tami Singleton:

How would you describe the impact that HEMLIBRA as a treatment option has really had on you as a physician, a hemophilia provider, a pediatric hematologist?

ON SCREEN:

The Impact of HEMLIBRA

Sanjay Ahuja:

I've been in practice with treating hemophilia patients for the last twenty years. Our staff at the hemophilia treatment center, including the nurses, our trainees, were all amazed at how a change in therapy was able to change the entire perspective on a chronic disorder such as hemophilia A. It has had a great impact on our functioning as a hemophilia treatment center as well.

Courtney Carr:

And going back to the first patient that I ever started on HEMLIBRA, when he was eight years old and he came back and said, "I've had significant improvement," and hearing so many patients tell that same story, I think that's the benefit of HEMLIBRA.

ON SCREEN: 

Individual results may vary. Reference the full clinical trial results in the Prescribing Information.

Select Important Safety Information

Warnings and Precautions: Thrombotic Microangiopathy (TMA) and Thromboembolism Associated with HEMLIBRA and aPCC
In clinical trials, TMA was reported in 0.8% of patients (3/391) and thrombotic events were reported in 0.5% of patients (2/391). In patients who received at least one dose of aPCC, TMA was reported in 8.1% of patients (3/37) and thrombotic events were reported in 5.4% of patients (2/37). Patients with TMA presented with thrombocytopenia, microangiopathic hemolytic anemia, and acute kidney injury, without severe deficiencies in ADAMTS13.

Louis:

I think beforehand I tried to not hide the fact that I had hemophilia, but it was more of like, it felt like it was a detrimental factor in my life and it was just something I had to deal with. And I really truly believe that switching over to HEMLIBRA made a huge impact in me accepting who I am as a hemophiliac, what I can do and what's possible in my life and made me much more comfortable with who I am as a person.

Dr. Tami Singleton:

So, where you are now, who would you say would be an appropriate patient in terms of you prescribing HEMLIBRA? Who would you recommend HEMLIBRA to or for?

ON SCREEN:

Appropriate Candidates

Courtney Carr:

I think honestly all patients with hemophilia A. Any age, any severity, I think all patients deserve to know about HEMLIBRA.

ON SCREEN:

HEMLIBRA 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 with or without factor VIII inhibitors.

Sanjay Ahuja:

I don't see a reason why the therapy with HEMLIBRA should not be offered to each and every patient of hemophilia A.

Dr. Tami Singleton:

What do you think that someone else might like to hear or need to hear that very first time they hear the word HEMLIBRA, subcutaneous injection, novel therapy for hemophilia A?

ON SCREEN:

From One Patient To Another

Louis:

Don't be afraid to try something different with your hemophilia treatment, you know. It's one of those things that you have to learn to evolve and grow in different times but I wish more people could hear that.

Dr. Tami Singleton:

These three perspectives really painted a picture. While Sanjay and Courtney began with those obvious types of patients, those with inhibitors, and of course those with venous access issues, but both of their perspectives shifted after seeing the reduction in bleeds needing treatment in those patients and how well the dosing and administration aspect fit into their lives.

ON SCREEN:

Individual results may vary. Reference the full clinical trial results in the Prescribing Information.

Dr. Tami Singleton:

As for Louis, he didn't have any major issues with his current therapy. He simply wanted to take advantage of something that he believed could help him maintain a healthy lifestyle. None of these responders see HEMLIBRA as a backup treatment option anymore.

ON SCREEN:

Why would I expand my use of HEMLIBRA beyond the obvious cases?

Dr. Tami Singleton:

So, to answer the question we came here for, why expand your use of HEMLIBRA outside of the obvious cases, well, from what we've heard, HEMLIBRA raises the bar in terms of bleed protection and allows many patients to go from infusing multiple times a week to a subcutaneous injection once a week, once every two weeks or once every four weeks. So, why not offer that to more patients? It may impact them more than you realize. If you have a tough question about HEMLIBRA, contact your Genentech representative. We want to dig into it.

ON SCREEN:

  • Raises the bar in bleed protection
    • HAVEN 3: 56% (QW) and 60% (Q2W) of adults and adolescents without FVIII had zero treated bleeds vs 0% with no prophylaxis and randomized comparison
    • HAVEN 4: 56% (Q4W) of adults with or without inhibitors
  • Can be taken once a week, once every 2 weeks, or once every 4 weeks, after the 4 weekly loading doses

VO:

HEMLIBRA 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 with or without factor VIII inhibitors. Important safety information. Boxed Warning. Thrombotic microangiopathy and thromboembolism. Cases of thrombotic microangiopathy and thrombotic events were reported when on average a cumulative amount of >100 units per kilogram per 24 hours of activated prothrombin complex concentrate, aPCC, was administered for 24 hours or more to patients receiving HEMLIBRA prophylaxis. Monitor for the development of thrombotic microangiopathy and thrombotic events if aPCC is administered. Discontinue aPCC and suspend dosing of HEMLIBRA if symptoms occur.

Warnings and precautions. Thrombotic microangiopathy, TMA, and thromboembolism associated With HEMLIBRA and aPCC. In clinical trials, TMA was reported in 0.8% of patients, three out of 391, and thrombotic events were reported in 0.5% of patients, two out of 391. In patients who received at least one dose of aPCC, TMA was reported in 8.1% of patients, three out of 37, and thrombotic events were reported in 5.4% of patients, two out of 37. Patients with TMA presented with thrombocytopenia, microangiopathic hemolytic anemia, and acute kidney injury, without severe deficiencies in ADAMTS13.

Consider the benefits and risks if aPCC must be used in a patient receiving HEMLIBRA prophylaxis. Monitor for the development of TMA and/or thromboembolism when administering aPCC. Immediately discontinue aPCC and interrupt HEMLIBRA prophylaxis if clinical symptoms, imaging, or laboratory findings consistent with TMA and/or thromboembolism occur, and manage as clinically indicated. Consider the benefits and risks of resuming HEMLIBRA prophylaxis following complete resolution of TMA and/or thrombotic events on a case-by-case basis.

Laboratory coagulation test interference. HEMLIBRA 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 activity. Therefore, intrinsic pathway clotting-based coagulation laboratory test results in patients who have been treated with HEMLIBRA prophylaxis should not be used to monitor HEMLIBRA activity, determine dosing for factor replacement or anti-coagulation, or measure factor VIII inhibitor titers.

Results affected by HEMLIBRA: aPTT; Bethesda assays, clotting-based, for factor VIII inhibitor titers; one-stage, aPTT-based single-factor assays; aPTT-based Activated Protein C Resistance, APC-R; ACT. Results unaffected by HEMLIBRA: Bethesda assays, bovine chromogenic, for Factor VIII inhibitor titers; thrombin time, TT; one-stage, prothrombin time, PT-based single-factor assays; chromogenic-based single-factor assays other than factor VIII, see Drug Interactions for factor VIII chromogenic activity assay considerations; immuno-based assays, for example, ELISA, turbidimetric methods; genetic tests of coagulation factors, for example, Factor V Leiden, Prothrombin 20210.

Most common adverse reactions. The most common adverse reactions, incidence ≥10%, are injection site reactions, headache, and arthralgia.

Adverse reactions. Characterization of aPCC treatment in pooled clinical trials. There were 130 instances of aPCC treatment in 37 patients, of which 13 instances, 10%, consisted of on average a cumulative amount of >100 units per kilogram per 24 hours of aPCC for 24 hours or more; two of the 13 were associated with thrombotic events and three of the 13 were associated with TMA. No TMA or thrombotic events were associated with the remaining instances of aPCC treatment.

Injection site reactions. In total, 85 patients, 22%, reported injection site reactions, ISRs. All ISRs observed in HEMLIBRA clinical trials were reported as mild to moderate intensity and 93% resolved without treatment. The commonly reported ISR symptoms were injection site erythema, 11%, injection site pruritus, 4%, and injection site pain, 4%.

Other less common, <1%, reactions. Rhabdomyolysis was reported in two adult patients with asymptomatic elevations in serum creatine kinase without associated renal or musculoskeletal symptoms. In both instances, the event occurred following an increase in physical activity.

Drug interactions. Clinical experience suggests that a drug interaction exists with HEMLIBRA and aPCC.

Pregnancy, lactation, females and males of reproductive potential. Women of childbearing potential should use contraception while receiving HEMLIBRA. It is not known whether HEMLIBRA can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. HEMLIBRA should be used during pregnancy only if the potential benefit for the mother outweighs the risk to the fetus. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for HEMLIBRA and any potential adverse effects on the breastfed child from HEMLIBRA or from the underlying maternal condition.

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 for additional Important Safety Information, including Boxed Warning.

Individual results may vary. Not all patients in the clinical trials had zero bleeds. See results for clinical trial patients with factor VIII inhibitors here, or without factor VIII inhibitors here.
The HEMLIBRA community members shown have been compensated for their participation.

Indication & Important Safety Information

Indication
HEMLIBRA 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 with or without factor VIII inhibitors.

Important Safety Information
Boxed 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 (aPCC) was administered for 24 hours or more to patients receiving HEMLIBRA prophylaxis. Monitor for the development of thrombotic microangiopathy and thrombotic events if aPCC is administered. Discontinue aPCC and suspend dosing of HEMLIBRA if symptoms occur. 

Warnings and Precautions
Thrombotic Microangiopathy (TMA) and Thromboembolism Associated With HEMLIBRA and aPCC
In clinical trials, TMA was reported in 0.8% of patients (3/391) and thrombotic events were reported in 0.5% of patients (2/391). In patients who received at least one dose of aPCC, TMA was reported in 8.1% of patients (3/37) and thrombotic events were reported in 5.4% of patients (2/37). Patients with TMA presented with thrombocytopenia, microangiopathic hemolytic anemia, and acute kidney injury, without severe deficiencies in ADAMTS13.

Consider the benefits and risks if aPCC must be used in a patient receiving HEMLIBRA prophylaxis. Due to the long half-life of HEMLIBRA, the potential for an interaction with aPCC may persist for up to 6 months after the last dose. Monitor for the development of TMA and/or thromboembolism when administering aPCC. Immediately discontinue aPCC and interrupt HEMLIBRA prophylaxis if clinical symptoms, imaging, or laboratory findings consistent with TMA and/or thromboembolism occur, and manage as clinically indicated. Consider the benefits and risks of resuming HEMLIBRA prophylaxis following complete resolution of TMA and/or thrombotic events on a case-by-case basis.

Laboratory Coagulation Test Interference
HEMLIBRA 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. Therefore, intrinsic pathway clotting-based coagulation laboratory test results in patients who have been treated with HEMLIBRA prophylaxis should not be used to monitor HEMLIBRA activity, determine dosing for factor replacement or anti-coagulation, or measure FVIII inhibitor titers.

Results affected by HEMLIBRA: aPTT; Bethesda assays (clotting-based) for FVIII inhibitor titers; one-stage, aPTT-based single-factor assays; aPTT-based Activated Protein C Resistance (APC-R); ACT.

Results unaffected by HEMLIBRA: Bethesda assays (bovine chromogenic) for FVIII inhibitor titers; thrombin time (TT); one-stage, prothrombin time (PT)-based single-factor assays; chromogenic-based single-factor assays other than FVIII (see Drug Interactions for FVIII chromogenic activity assay considerations); immuno-based assays (ie, ELISA, turbidimetric methods); genetic tests of coagulation factors (eg, Factor V Leiden, Prothrombin 20210).

Most Common Adverse Reactions
The most common adverse reactions (incidence ≥10%) are injection site reactions, headache, and arthralgia.

Adverse Reactions
Characterization of aPCC Treatment in Pooled Clinical Trials
There were 130 instances of aPCC treatment in 37 patients, of which 13 instances (10%) consisted of on average a cumulative amount of >100 U/kg/24 hours of aPCC for 24 hours or more; 2 of the 13 were associated with thrombotic events and 3 of the 13 were associated with TMA. No TMA or thrombotic events were associated with the remaining instances of aPCC treatment.

Injection Site Reactions
In total, 85 patients (22%) reported injection site reactions (ISRs). All ISRs observed in HEMLIBRA clinical trials were reported as mild to moderate intensity and 93% resolved without treatment. The commonly reported ISR symptoms were injection site erythema (11%), injection site pruritus (4%), and injection site pain (4%).

Other Less Common (<1%) Reactions
Rhabdomyolysis was reported in 2 adult patients with asymptomatic elevations in serum creatine kinase without associated renal or musculoskeletal symptoms. In both instances, the event occurred following an increase in physical activity.

Drug Interactions
Clinical experience suggests that a drug interaction exists with HEMLIBRA and aPCC.

Pregnancy, Lactation, Females and Males of Reproductive Potential
Women of childbearing potential should use contraception while receiving HEMLIBRA. It is not known whether HEMLIBRA can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. HEMLIBRA should be used during pregnancy only if the potential benefit for the mother outweighs the risk to the fetus. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for HEMLIBRA and any potential adverse effects on the breastfed child from HEMLIBRA or from the underlying maternal condition.

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 for additional Important Safety Information, including Boxed WARNING.

    • Data on file. Genentech, Inc.

      Data on file. Genentech, Inc.

    • Our commitment to provide transparent and timely safety information about emicizumab-kxwh. Genentech, Inc. https://www.emicizumabinfo.com/content/emicizumabinfo/en_us/patient.html#. Accessed August 25, 2020.

      Our commitment to provide transparent and timely safety information about emicizumab-kxwh. Genentech, Inc. https://www.emicizumabinfo.com/content/emicizumabinfo/en_us/patient.html#. Accessed August 25, 2020.

    • Chugai Pharmaceutical Co., Ltd. Randomized, placebo-controlled, double-blind, single ascending dose study and open-label multiple ascending dose study. https://www.clinicaltrials.jp/user/showCteDetailE.jsp?japicId=JapicCTI-121934. Main ID: JPRN-JapicCTI-121934. Accessed August 25, 2020.

      Chugai Pharmaceutical Co., Ltd. Randomized, placebo-controlled, double-blind, single ascending dose study and open-label multiple ascending dose study. https://www.clinicaltrials.jp/user/showCteDetailE.jsp?japicId=JapicCTI-121934. Main ID: JPRN-JapicCTI-121934. Accessed August 25, 2020.

    • Chugai Pharmaceutical Co., Ltd. Extension study of the phase 1 study of ACE910. https://www.clinicaltrials.jp/user/showCteDetailE.jsp?japicId=JapicCTI-132195. Main ID: JPRN-JapicCTI-132195. Accessed August 25, 2020.

      Chugai Pharmaceutical Co., Ltd. Extension study of the phase 1 study of ACE910. https://www.clinicaltrials.jp/user/showCteDetailE.jsp?japicId=JapicCTI-132195. Main ID: JPRN-JapicCTI-132195. Accessed August 25, 2020.

    • HEMLIBRA [package insert]. South San Francisco, CA: Genentech, Inc.

      HEMLIBRA [package insert]. South San Francisco, CA: Genentech, Inc.

    • National Hemophilia Foundation. MASAC update on the approval and availability of the new treatment: Emicizumab (HEMLIBRA), for persons with hemophilia A with inhibitors to factor VIII: Interim guidance on acute bleed management and use of laboratory assays. November 24, 2017; New York, NY.

      National Hemophilia Foundation. MASAC update on the approval and availability of the new treatment: Emicizumab (HEMLIBRA), for persons with hemophilia A with inhibitors to factor VIII: Interim guidance on acute bleed management and use of laboratory assays. November 24, 2017; New York, NY.

    • Kitazawa T, Esaki K, Tachibana T, et al. Factor VIIIa-mimetic cofactor activity of a bispecific antibody to factors IX/IXa and X/Xa, emicizumab, depends on its ability to bridge the antigens. Thromb Haemost. 2017;117(7):1348-1357.

      Kitazawa T, Esaki K, Tachibana T, et al. Factor VIIIa-mimetic cofactor activity of a bispecific antibody to factors IX/IXa and X/Xa, emicizumab, depends on its ability to bridge the antigens. Thromb Haemost. 2017;117(7):1348-1357.

    • Young G, Liesner R, Chang T, et al. A multicenter, open-label phase 3 study of emicizumab prophylaxis in children with hemophilia A with inhibitors. Blood. 2019;134(24):2127-2138.

      Young G, Liesner R, Chang T, et al. A multicenter, open-label phase 3 study of emicizumab prophylaxis in children with hemophilia A with inhibitors. Blood. 2019;134(24):2127-2138.

    • Shima M, Hanabusa H, Taki M, et al. Long-term safety and efficacy of emicizumab in a phase 1/2 study in patients with hemophilia A with or without inhibitors. Blood Adv. 2017;1(22):1891-1899.

      Shima M, Hanabusa H, Taki M, et al. Long-term safety and efficacy of emicizumab in a phase 1/2 study in patients with hemophilia A with or without inhibitors. Blood Adv. 2017;1(22):1891-1899.

    • Shima M, Nagao A, Masashi T, et al. Long-term safety and efficacy of emicizumab for up to >5 years in a phase 1/2 study in patients with severe hemophilia A. Poster presented at: International Society on Thrombosis and Haemostasis 2020 Virtual Congress; July 12–14, 2020.

      Shima M, Nagao A, Masashi T, et al. Long-term safety and efficacy of emicizumab for up to >5 years in a phase 1/2 study in patients with severe hemophilia A. Poster presented at: International Society on Thrombosis and Haemostasis 2020 Virtual Congress; July 12–14, 2020.

    • Wang S, Zhao X, Wang X, et al. A randomized, multicenter, open-label, phase III clinical trial to evaluate the efficacy, safety, and pharmacokinetics of prophylactic emicizumab versus no prophylaxis in persons with hemophilia A in the Asia-Pacific region (HAVEN 5). Poster presented at: International Society on Thrombosis and Haemostasis 2020 Virtual Congress; July 12–14, 2020.

      Wang S, Zhao X, Wang X, et al. A randomized, multicenter, open-label, phase III clinical trial to evaluate the efficacy, safety, and pharmacokinetics of prophylactic emicizumab versus no prophylaxis in persons with hemophilia A in the Asia-Pacific region (HAVEN 5). Poster presented at: International Society on Thrombosis and Haemostasis 2020 Virtual Congress; July 12–14, 2020.

    • Shima M, Nogami K, Nagami S, et al. A multicentre, open-label study of emicizumab given every 2 or 4 weeks in children with severe haemophilia A without inhibitors. Haemophilia. 2019;25(6):979-987.

      Shima M, Nogami K, Nagami S, et al. A multicentre, open-label study of emicizumab given every 2 or 4 weeks in children with severe haemophilia A without inhibitors. Haemophilia. 2019;25(6):979-987.

    • Jiménez-Yuste V, Klamroth R, Castaman G, et al. Second interim analysis results from the STASEY trial: a single-arm, multicenter, open-label, phase III clinical trial to evaluate the safety and tolerability of emicizumab prophylaxis in people with hemophilia A (PwHA) with FVIII inhibitors. Poster presented at: International Society on Thrombosis and Haemostasis 2020 Virtual Congress; July 12–14, 2020.

      Jiménez-Yuste V, Klamroth R, Castaman G, et al. Second interim analysis results from the STASEY trial: a single-arm, multicenter, open-label, phase III clinical trial to evaluate the safety and tolerability of emicizumab prophylaxis in people with hemophilia A (PwHA) with FVIII inhibitors. Poster presented at: International Society on Thrombosis and Haemostasis 2020 Virtual Congress; July 12–14, 2020.

    • Callaghan M, Negrier C, Paz-Priel I, et al. Emicizumab treatment is efficacious and well tolerated long term in persons with haemophilia (PwHA) with or without FVIII inhibitors: pooled data from four HAVEN studies. Slide deck presented at: International Society on Thrombosis and Haemostasis 2019 Congress; July 6–10, 2019; Melbourne, Australia.

      Callaghan M, Negrier C, Paz-Priel I, et al. Emicizumab treatment is efficacious and well tolerated long term in persons with haemophilia (PwHA) with or without FVIII inhibitors: pooled data from four HAVEN studies. Slide deck presented at: International Society on Thrombosis and Haemostasis 2019 Congress; July 6–10, 2019; Melbourne, Australia.

    • Oldenburg J, Mahlangu JN, Kim B, et al. Emicizumab prophylaxis in hemophilia A with inhibitors. N Engl J Med. 2017;377(9):809-818.

      Oldenburg J, Mahlangu JN, Kim B, et al. Emicizumab prophylaxis in hemophilia A with inhibitors. N Engl J Med. 2017;377(9):809-818.

    • Young G, Liesner R, Sidonio R Jr, et al. Emicizumab prophylaxis provides flexible and effective bleed control in children with hemophilia A with inhibitors: results from the HAVEN 2 study. Presented at: ASH 60th Annual Meeting of the American Society of Hematology; December 1–4, 2018; San Diego, CA.

      Young G, Liesner R, Sidonio R Jr, et al. Emicizumab prophylaxis provides flexible and effective bleed control in children with hemophilia A with inhibitors: results from the HAVEN 2 study. Presented at: ASH 60th Annual Meeting of the American Society of Hematology; December 1–4, 2018; San Diego, CA.

    • Di Minno A, Spadarella G, Nardone A, et al. Attempting to remedy sub-optimal medication adherence in haemophilia: the rationale for repeated ultrasound visualisations of the patient’s joint status. Blood Rev. 2019;33:106-119.

      Di Minno A, Spadarella G, Nardone A, et al. Attempting to remedy sub-optimal medication adherence in haemophilia: the rationale for repeated ultrasound visualisations of the patient’s joint status. Blood Rev. 2019;33:106-119.

    • Rocino A, Franchini M, Coppola A. Treatment and prevention of bleeds in haemophilia patients with inhibitors to factor VIII/IX. J Clin Med. 2017;6(4):46.

      Rocino A, Franchini M, Coppola A. Treatment and prevention of bleeds in haemophilia patients with inhibitors to factor VIII/IX. J Clin Med. 2017;6(4):46.

    • Schrijvers LH, Schuurmans MJ, Fischer K. Promoting self-management and adherence during prophylaxis: evidence-based recommendations for haemophilia professionals. Haemophilia. 2016;22(4):499-506.

      Schrijvers LH, Schuurmans MJ, Fischer K. Promoting self-management and adherence during prophylaxis: evidence-based recommendations for haemophilia professionals. Haemophilia. 2016;22(4):499-506.

    • Manco-Johnson MM, Abshire TC, Shapiro AD, et al. Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia. N Engl J Med. 2007;357(6):535-544.

      Manco-Johnson MM, Abshire TC, Shapiro AD, et al. Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia. N Engl J Med. 2007;357(6):535-544.

    • National Hemophilia Foundation. Recommendation on the use and management of emicizumab-kxwh (HEMLIBRA®) for hemophilia A with and without inhibitors. December 6, 2018; New York, NY.

      National Hemophilia Foundation. Recommendation on the use and management of emicizumab-kxwh (HEMLIBRA®) for hemophilia A with and without inhibitors. December 6, 2018; New York, NY.

    • FDA approves Genentech’s HEMLIBRA (emicizumab-kxwh) for hemophilia A without factor VIII inhibitors. [press release]. South San Francisco, CA: Genentech; October 4, 2018.

      FDA approves Genentech’s HEMLIBRA (emicizumab-kxwh) for hemophilia A without factor VIII inhibitors. [press release]. South San Francisco, CA: Genentech; October 4, 2018.

    • Hoffmann-La Roche. A study to evaluate the efficacy, safety, and pharmacokinetics of prophylactic emicizumab versus no prophylaxis in hemophilia A participants with inhibitors (HAVEN 1). https://clinicaltrials.gov/ct2/show/NCT02622321. NLM identifier: NCT02622321. Accessed August 25, 2020.

      Hoffmann-La Roche. A study to evaluate the efficacy, safety, and pharmacokinetics of prophylactic emicizumab versus no prophylaxis in hemophilia A participants with inhibitors (HAVEN 1). https://clinicaltrials.gov/ct2/show/NCT02622321. NLM identifier: NCT02622321. Accessed August 25, 2020.

    • Hoffmann-La Roche. A study of emicizumab administered subcutaneously (SC) in pediatric participants with hemophilia A and factor VIII (FVIII) inhibitors (HAVEN 2). https://clinicaltrials.gov/ct2/show/NCT02795767. NLM identifier: NCT02795767. Accessed August 25, 2020.

      Hoffmann-La Roche. A study of emicizumab administered subcutaneously (SC) in pediatric participants with hemophilia A and factor VIII (FVIII) inhibitors (HAVEN 2). https://clinicaltrials.gov/ct2/show/NCT02795767. NLM identifier: NCT02795767. Accessed August 25, 2020.

    • Hoffmann-La Roche. A clinical trial to evaluate prophylactic emicizumab versus no prophylaxis in hemophilia A participants without inhibitors (HAVEN 3). https://clinicaltrials.gov/ct2/show/NCT02847637. NLM identifier: NCT02847637. Accessed August 25, 2020.

      Hoffmann-La Roche. A clinical trial to evaluate prophylactic emicizumab versus no prophylaxis in hemophilia A participants without inhibitors (HAVEN 3). https://clinicaltrials.gov/ct2/show/NCT02847637. NLM identifier: NCT02847637. Accessed August 25, 2020.

    • Hoffmann-La Roche. A study to evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of emicizumab given every 4 weeks in participants with hemophilia A (HAVEN 4). https://clinicaltrials.gov/ct2/show/NCT03020160. NLM identifier: NCT03020160. Accessed August 25, 2020.

      Hoffmann-La Roche. A study to evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of emicizumab given every 4 weeks in participants with hemophilia A (HAVEN 4). https://clinicaltrials.gov/ct2/show/NCT03020160. NLM identifier: NCT03020160. Accessed August 25, 2020.

    • Kruse-Jarres R, Callaghan MU, Croteau SE, et al. Surgical experience in two multicenter, open-label phase 3 studies of emicizumab in persons with hemophilia A with inhibitors (HAVEN 1 and HAVEN 2) [abstract]. Presented at: 59th Annual Meeting of the American Society of Hematology; December 9-12, 2017; Atlanta, GA.

      Kruse-Jarres R, Callaghan MU, Croteau SE, et al. Surgical experience in two multicenter, open-label phase 3 studies of emicizumab in persons with hemophilia A with inhibitors (HAVEN 1 and HAVEN 2) [abstract]. Presented at: 59th Annual Meeting of the American Society of Hematology; December 9-12, 2017; Atlanta, GA.

    • Mahlangu J, Oldenburg J, Paz-Priel I, et al. Emicizumab prophylaxis in patients who have hemophilia A without inhibitors. N Engl J Med. 2018;379(9):811-822.

      Mahlangu J, Oldenburg J, Paz-Priel I, et al. Emicizumab prophylaxis in patients who have hemophilia A without inhibitors. N Engl J Med. 2018;379(9):811-822.

    • HEMLIBRA Summary of Product Characteristics. Roche Registration Limited; 2019.

      HEMLIBRA Summary of Product Characteristics. Roche Registration Limited; 2019.

    • Santagostino E, Oldenburg J, Chang T, et al. Surgical experience from four phase III studies (HAVEN 1–4) of emicizumab in persons with haemophilia A (PwHA) with or without FVIII inhibitors. Slide deck presented at: International Society on Thrombosis and Haemostasis 2019 Congress; July 6–10, 2019; Melbourne, Australia.

      Santagostino E, Oldenburg J, Chang T, et al. Surgical experience from four phase III studies (HAVEN 1–4) of emicizumab in persons with haemophilia A (PwHA) with or without FVIII inhibitors. Slide deck presented at: International Society on Thrombosis and Haemostasis 2019 Congress; July 6–10, 2019; Melbourne, Australia.

    • Sampei Z, Igawa T, Soeda T, et al. Identification and multidimensional optimization of an asymmetric bispecific IgG antibody mimicking the function of factor VIII cofactor activity. PLoS One. 2013;8(2):e57479.

      Sampei Z, Igawa T, Soeda T, et al. Identification and multidimensional optimization of an asymmetric bispecific IgG antibody mimicking the function of factor VIII cofactor activity. PLoS One. 2013;8(2):e57479.

    • Santagostino E, Parnes A, Dhalluin C, et al. Surgical procedures in persons with haemophilia A (PwHA) without inhibitors receiving emicizumab – experience from the HAVEN 3 study. Presented at: 12th Annual Congress of the European Association of Haemophilia and Allied Disorders (EAHAD); February 6–8, 2019; Prague, Czech Republic.

      Santagostino E, Parnes A, Dhalluin C, et al. Surgical procedures in persons with haemophilia A (PwHA) without inhibitors receiving emicizumab – experience from the HAVEN 3 study. Presented at: 12th Annual Congress of the European Association of Haemophilia and Allied Disorders (EAHAD); February 6–8, 2019; Prague, Czech Republic.