HEMLIBRA Dosing Options

The freedom to choose a dosing option that works best for your patient1,5

“You could literally go from infusing yourself to now injecting just twice a month.”

—Gabe, 36-year-old with hemophilia A without FVIII inhibitors, Texas

 

Gabe administers Q2W dosing after his 4 QW loading doses.
Please see HEMLIBRA Instructions for Use for full dosing and administration information.

QW=once weekly; Q2W=once every 2 weeks.

Explore options with the Dosing Calculator.

The majority of patients had zero treated bleeds, regardless of dosing schedule

For patients starting HEMLIBRA, they should receive a loading dose of 3 mg/kg once weekly for the first 4 weeks.

  • The prophylactic use of FVIII products may be continued during the first week of HEMLIBRA prophylaxis
  • Discontinue the prophylactic use of BPAs the day before starting HEMLIBRA prophylaxis

At Week 5, your patient starts on 1 of the chosen maintenance dosing options.

HEMLIBRA 1.5 mg/kg every week.
HEMLIBRA 3 mg/kg every 2 weeks.
HEMLIBRA 6 mg/kg every 4 weeks.

"Those 3 dosing options provide some flexibility."
—Michael Callaghan, MD, Children’s Hospital of Michigan

  • If a dose of HEMLIBRA is missed, administer as soon as possible and then return to usual dosing schedule. Do not administer 2 doses on the same day to make up for a missed dose
  • Note: Same weight-based dosage for all age ranges

Drug-level monitoring is not required for routine HEMLIBRA prophylaxis

Starting HEMLIBRA Quick Reference Guide

Before your patients start HEMLIBRA, you can help them prepare. Download the Starting HEMLIBRA Quick Reference Guide  to help your patients stay on track with their loading and maintenance doses and create their breakthrough bleed plan.

Why would I encourage a patient to try a treatment outside their comfort zone?

Featuring Dr. Tami Singleton, Dr. Mike Tarantino, nurse Kim Schafer, and Gabe, who has hemophilia A.

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 >100 units per kilogram per day of activated prothrombin complex concentrate, aPCC, was administered for 24 hours or more to patients receiving HEMLIBRA prophylaxis.

ON SCREEN:
HEMLIBRA presents an investigative documentary series: TOUGH QUESTIONS

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 Encourage a Patient To Try Treatment Outside Of Their Comfort Zone?

Dr. Tami Singleton:
This question is one that comes up in a variety of therapeutic areas. Why would you encourage a patient to try a therapy that is outside their comfort zone?

ON SCREEN:
First and only Subcutaneous Prophylaxis

Dr. Tami Singleton:
HEMLIBRA is the first and only subcutaneous prophylaxis for the treatment of hemophilia A. And for people who've been infusing with factor VIII for 20 or 30 years, it could feel a little unnerving to try something so different from what they're used to. So let's see what the community has to say about it. Let's meet up with these respondents and dig just a little deeper into their answers to this question. So, I am especially honored today to have Dr. Mike Tarantino with us.

Dr. Mike Tarantino:
Yeah, I'm officially one of the old timers in the field now. I've been in hematology for 30 years.

Dr. Tami Singleton:
So, you actually would be the perfect person to ask this question.

ON SCREEN:
Initial Concerns With HEMLIBRA

Dr. Tami Singleton:
Initially, what concerns did you have regarding switching your patients to a subcutaneous therapy that was really different than anything that we have experienced in our community before?

Dr. Mike Tarantino:
You know, whenever a new product comes around, there's always mixed feelings. Our patients in the bleeding disorders community are very cautious about new developments and want to be sure that it reaches a certain metric of safety for them.

Kim Schafer:
I must admit I did initially have some hesitation and some concerns mainly because HEMLIBRA is a novel therapy.

Dr. Mike Tarantino:
There were some unknowns at the time. And I think that, you know, there was very nice and good open communication among the hemophilia and bleeding disorders community, among the manufacturer and us and the community. So I think it really helped over time really to sort of settle those uncertainties.

VO:
Monitor for the development of thrombotic microangiopathy and thrombotic events if 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.

Dr. Tami Singleton:
So walk me through how you would typically have a conversation with a patient about new things that are happening in the world of hemophilia A.

ON SCREEN:
Ongoing Dialogue and Education

Dr. Mike Tarantino:
I think my job in that situation is just to be sure that everybody is informed, that their questions are answered, that their uncertainties or fears that they might have are really, you know, based in things that are actual. And if not, we have discussion about it.

Kim Schafer:
Many patients come in for their annual visit and they want to come in and say hello, do what they need to do and say goodbye and not see you until next year. There is opportunity to help these patients understand that the old way can be improved a little bit.

ON SCREEN:
Primary endpoint was studied against patients not on prophylaxis.

Dr. Tami Singleton:
You review any clinical data with patients that you may find, you know, sort of helpful in terms of helping them with some of the fears or resistance that they have specifically with HEMLIBRA?

Dr. Mike Tarantino:
We firmly believe in the comprehensive care model that the patient is part of the comprehensive care team. So we have ongoing dialogue and education that really works both ways. The long half-life, that's something that's visually very cogent and it's very impactful when a patient sees that.

ON SCREEN:
A Half-Life Measured in Weeks Not Hours

  • Sustained therapeutic drug levels across dosing options

Kim Schafer:
I've also heard patients say, "I'm interested, but I'm not really looking to change my treatment regimen right now." And at that point I will use the clinical data from HEMLIBRA so that they can really look at the number and see for themselves, you know, what those improvements from the clinical study were.

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

Kim Schafer:
I think that's really kind of the first step that I take for a lot of these patients. When we delve into actually how they're doing, there may be room for improvements with their treatment.

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

Dr. Tami Singleton:
Hi, Gabe. It's great to see you again. I know you had a great routine before HEMLIBRA, right, but it sounds like you were pretty structured and comfortable, would you say?

Gabe:
My life for a long time was very structured. I was on a long acting factor for about five years before I switched over to HEMLIBRA and I had a pretty set schedule.

Dr. Tami Singleton:
So, walk us through a little bit in terms of, how did you hear about HEMLIBRA for the first time?

Gabe:
My mom works for a pharmacy company, so she hears about new products all the time, and she's very up to date on everything. And me obviously being very rebellious, I kind of just shrugged her off and blew it off, to be honest with you. I was just very skeptical. I was very comfortable in my routine. And honestly, I was just not really open to changing that up.

Dr. Tami Singleton:
I wanted to just dive a little deeper on that because that's a really big deal for so many people, right? That skepticism, that anxiety. What was it for you in particular, like focusing on that skepticism, do you think that sort of tipped the scales for you?

Gabe:
I always felt that if I already had a good thing, why rock the boat and why switch things? I can tell you this Dr. Singleton though. Once I got myself educated, my skepticism became complete excitement.

ON SCREEN:

Revisiting the Conversation

Dr. Tami Singleton:
So, I'm sure there's more than one patient, but can you describe that one patient who was very reluctant to change to HEMLIBRA, but ultimately did. And how did you address the fears, concerns or anxieties related to that patient and that fear?

Dr. Mike Tarantino:
I think we honestly have three or four of those patients for whom HEMLIBRA was a non-starter in our first conversations. But then over time with dialogue with us, with talking to their colleagues and friends in the hemophilia bleeding disorders community, with other people having success, they've come around. By our metric of, you know, a reduction in their annualized bleeding rate, the type of breakthrough bleeding, if they have any, being reduced is fair to say a success.

ON SCREEN:

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

Dr. Mike Tarantino:
So I have had patients at the very beginning that said no way and are now happily getting HEMLIBRA.

ON SCREEN:

  • Intra-patient comparison: Patients experience 68% fewer treated bleeds
    • HAVEN 3 HEMLIBRA vs prior FVIII prophylaxis. Median efficacy: 34 weeks
      • Prior FVIII Prophylaxis (N=48): 4.8 ABR (3.2; 7.1)
      • HEMLIBRA QW (N=48): 1.5 ABR (1.0; 2.3)
      • 68% fewer bleeds in HEMLIBRA vs FVIII Prophylaxis

Dr. Tami Singleton:
The HAVEN 3 study of people without inhibitors included an intra-patient comparison. Of people who were on factor VIII prophylaxis for at least 24 weeks. The study found that those who switched to HEMLIBRA had 68% fewer treated bleeds over a medium period of 34 weeks.

VO:
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.

Dr. Tami Singleton:
Why do you think it's important to push through that resistance that may really be laced with fear or something else as we're trying to provide great care for our patients with hemophilia A?

Kim Schafer:
There's a lot of fear and anxiety that might come about just from the simple act of change itself. If you end up stopping it because the patient says no initially, you don't really get anywhere the next time you see the patient. But if I can be there to help them take that first step so that they can feel better about their treatments, then I think I've done my job as a provider and I can go to bed at night knowing that I made a difference, which is really what I want to do.

Dr. Mike Tarantino:
If I strongly think that it's in the patient's best interest to switch to HEMLIBRA, then I'm really going to, like, give it effort, but I'm going to give it time and I'm going to really revisit and make sure that the patient knows if there was something that was really holding them back before, have we gone through that and have we answered all the questions that they have and really maybe dispelled misconceptions even in our effort to really get them on what we think might be better therapy for them.

ON SCREEN:
Testimony to HEMLIBRA

Dr. Tami Singleton:
I think that we have a healthy appreciation for the struggles, trials, tribulations, you know, things that people have gone through in this community. So, to say that you're a little anxious or nervous about something new I think would be a little bit of an understatement and totally, totally justified, right? So, what would you say to someone who's like you?

Gabe:
I heard this from a coach of mine when I was growing up. He said fear is false evidence appearing real. And one of the things that I understood was I couldn't let fear stop me, that I had to get myself educated. So I would say for anybody who is in my situation or parents that may have a young child is get yourself educated, do your own research, do your own interviews. Talk to people within the community that are involved, and our hemophilia community has a lot of people that are willing to share their testimony with you.

Dr. Tami Singleton:
We live in a time where medical advancements are happening right before our eyes. But what excites us as healthcare providers may seem scary to patients who've gotten used to treating their hemophilia A a certain way their whole lives. As Kim told us, patients can be set in their ways. They have to be ready for a change. What is our job is to continue to bring up the conversation of HEMLIBRA if we feel it's right for them. Mike told us that when he's met with resistance, he digs in to find out what the specific concerns are. And then he uses the data to help address those specific concerns, especially when it comes to safety.

ON SCREEN:
Why would I encourage a patient to try a treatment outside of their comfort zone?

Dr. Tami Singleton:
So to answer the question we came here for, why encourage a patient to try a treatment outside of their comfort zone, because for some, making a change can make a difference.

ON SCREEN:

  • Making a change can make a difference

Dr. Tami Singleton:
If you have a tough question about HEMLIBRA, contact your Genentech representative, we want to dig into it.

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.

VO:
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.

VO:
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.

VO:
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.

VO:
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.

VO:
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.

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

VO:
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.

VO:
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%.

VO:
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.

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

VO:
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.

VO:
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.

VO:
Please see the HEMLIBRA full prescribing information for additional important safety information, including Boxed Warning.

Injecting HEMLIBRA
Learn more about injecting HEMLIBRA with a step-by-step video for your patients

BPA=bypassing agent; FVIII=factor VIII.

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.

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