In Patients Without FVIII Inhibitors

HEMLIBRA was studied in adult and adolescent hemophilia A patients with and without factor VIII inhibitors8


Aim for zero treated bleeds: The majority of patients on HEMLIBRA had zero bleeds requiring treatment with any dosing schedule5

Percentage of patients who had zero treated bleeds with HEMLIBRA (primary endpoint)

HEMLIBRA® (emicizumab-kxwh) Patients Without FVIII Inhibitors Haven 3 every week
HAVEN 3: HEMLIBRA EVERY WEEK*

in adults and adolescents without factor VIII inhibitors

(95% CI: 38.1; 72.1) (95% CI: 0; 18.5)

HEMLIBRA® (emicizumab-kxwh) Patients Without FVIII Inhibitors bleed chart every 2 weeks
HAVEN 3: HEMLIBRA EVERY 2 WEEKS*

in adults and adolescents without factor VIII inhibitors 

(95% CI: 42.1; 76.1) (95% CI: 0; 18.5)

HEMLIBRA® (emicizumab-kxwh) Patients Without FVIII Inhibitors haven 3 every four weeks
HAVEN 4: HEMLIBRA EVERY 4 WEEKS

in adults and adolescents with (n=5)
or without FVIII inhibitors (n=36)

(95% CI: 39.7; 71.5)

 

*The median efficacy period was up to 31 weeks.
The median efficacy period was 26 weeks.

In HAVEN 3 and 4, all groups on HEMLIBRA prophylaxis had a median ABR of 0 for treated bleeds


A long-term descriptive analysis of adults and adolescents without FVIII inhibitors on HEMLIBRA.14

Percentage of patients with zero treated bleeds measured in 24-week intervals over 144 weeks (HAVEN 3)

Why do groups differ in size?

Patients in the trial could choose to convert to a commercial drug (available for non-inhibitor patients in the US as of October 2018) at any time. Once a patient starts commercial therapy, they are excluded from subsequent treatment intervals. At the time of this analysis (May 2020), many patients had converted to a commercially available HEMLIBRA.


Benefit conclusions about the bleed rates over time with HEMLIBRA cannot be drawn.
  • These results include patients from all study arms, including those who crossed over to HEMLIBRA from the no-prophylaxis arm
Based on the calculated mean ABR for bleeds treated with coagulation factors.

Making a change can make a difference

Patients without FVIII inhibitors taking HEMLIBRA saw a 68% reduction in treated bleed rate vs prior FVIII prophylaxis.5

INTRA-PATIENT COMPARISON

HAVEN 3: HEMLIBRA vs prior FVIII prophylaxis
The median efficacy period was 34 weeks

  • Median ABR in the intra-patient comparison was 0 (IQR: 0; 2.1) with HEMLIBRA vs 1.8 (IQR: 0; 7.6) with prior FVIII prophylaxis

§ABR was calculated with a negative binomial regression model, accounting for the difference in follow-up times.

“I think you’ll agree, that this is also clinically important…to go from roughly 5 bleeds a year to 1–2 [treated] bleeds per year.”1
—Guy Young, MD, Keck School of Medicine of the University of Southern California


Make a choice for target joint health

Adults and adolescents without FVIII inhibitors (HAVEN 3) taking HEMLIBRA experienced fewer treated target joint|| bleeds after 24 weeks.5

RANDOMIZED COMPARISON

HEMLIBRA QW

95%

REDUCTION IN TREATED TARGET JOINT BLEEDS

(95% CI: 85.7%; 98.4%)
vs no prophylaxis
P<0.0001, n=36

RANDOMIZED COMPARISON

HEMLIBRA Q2W

95%

REDUCTION IN TREATED TARGET JOINT BLEEDS

(95% CI: 85.3%; 98.2%)
vs no prophylaxis
P<0.0001, n=35


A post hoc, descriptive analysis of target joint resolution in patients taking HEMLIBRA (HAVEN 3)14

99%

TARGET JOINT RESOLUTION

in patients taking HEMLIBRA

  • 96 evaluable patients# reported a combined total of 237 target joints at baseline
  • The median duration of exposure was 163 weeks
  • This analysis was conducted post hoc. There was no prespecified statistical procedure controlling for type 1 error rate
  • Such analyses do not ascertain whether the findings were attributable to treatment with HEMLIBRA, or merely due to chance, and are susceptible to bias. Conclusions based on this analysis may not be valid

Target joints were defined as major joints (eg, hip, elbow, wrist, shoulder, knee, and ankle) in which ≥3 spontaneous bleeds occurred over a 24-week period.14
Target joint resolution was defined as ≤2 spontaneous bleeding events in a 52-week period in a joint previously defined as a target joint.5
#Evaluable patients were those with ≥52 weeks of HEMLIBRA prophylaxis.

Why would I switch my patient who is well-controlled on factor, and who hasn’t asked to switch?

Featuring Dr. Tami Singleton, Dr. Erin Cockrell, nurse Maya Bloomberg, and Maria, a caregiver to her son, Carlos, 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 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.

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 bring up switching to a patient who is well-controlled on factor?

Dr. Tami Singleton:

Today's question is a tricky one. If a patient is well-controlled on their current therapy, why would I switch them to HEMLIBRA, especially if they didn't ask to switch? I sent this question out to different treaters in the hemophilia A community and people with hemophilia and got some interesting responses back. Seems like different people have different definitions of well-controlled. I'm going to speak to a few of these people and dig a little deeper into their thoughts on this topic.

Dr. Tami Singleton:

All right. Hi there, Erin. It is great to see you.

Dr. Tami Singleton:

How do you define well-controlled when you think about patients with hemophilia A?

ON SCREEN:

Defining Well-Controlled

Dr. Erin Cockrell:

My thought of well-controlled is kind of an all around picture, not just their number of treated bleeds that they've been experiencing or the lack thereof, but also how they're feeling about their care. Patients may think, oh, I have 1 treated bleed per month. That's good for me. Whereas as treaters we're thinking, no, it needs to be better than that.

Maya Bloomberg:

I personally define well-controlled as having less than 3 bleeds requiring treatment per year, but you did bring up a good point, how there really is no standard definition for what well-controlled means. So I think there definitely is a discrepancy between patients and providers and what patients think is well-controlled versus what is actually happening in reality.

Dr. Tami Singleton:

Do you have patients, as you're going through and educating patients about therapies that are available, that you probably think this is a kind of patient that they feel like they're doing well, you don't want to rock the boat, you know, in terms of offering them any new therapies or suggesting any changes, then how do you provide those details in terms of how you think it could help, you know, that particular patient?

ON SCREEN:

Bringing up HEMLIBRA

Dr. Erin Cockrell:

I don't think of it as, in terms of rocking the boat rather than educating our patients. It's our job as their providers to educate them on newer therapies.

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.

So when I'm educating patients about HEMLIBRA, educate them on how it is a novel agent and it works differently from prior therapies and that it has a much longer half-life. And so we're able to achieve this steady state of drug in their body.

ON SCREEN:

A Half-Life Measured in Weeks Not Hours

  • Sustained therapeutic drug levels across dosing options

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. 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.

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.

  • 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. Erin Cockrell:

I'm explaining the results of the clinical trials and that there were fewer treated bleeds that we saw compared to patients on prophylaxis.

Dr. Tami Singleton:

So can you think of any specific patients and they felt that they were well-controlled, but as you were digging a little deeper, you actually discovered, well, things are not really fine?

ON SCREEN:

Multidisciplinary Approach

Maya Bloomberg:

We know it… really is a multidisciplinary approach. And I think the more touch points of contact that these patients are having, the more information and more interesting insights we're able to gather.

Dr. Erin Cockrell:

Again, we all may get a little bit different picture of how the patient's doing. Sometimes they may feel more comfortable sharing with the social worker than with another member of our team. So they may get a different story than what I'm getting. And so in that regard, we kind of put all the pieces together and sum up exactly how well they're doing from the patient perspective.

Dr. Tami Singleton:

So you're a mom and your son has hemophilia A. Do you really think that your doctor had a true appreciation and understanding for the difficulty that you were experiencing and how it impacted you and how it impacted Carlos?

ON SCREEN:

Understanding the Need to Switch

Maria:

You know, and I appreciate my doctor because he knew the struggle that I was having. Being a single parent, sometimes it is difficult because you have to put your time, you know, have everything in order. And he understood my situation really well.

Dr. Tami Singleton:

How did you hear about HEMLIBRA? Did you bring it up to your doctor? Did he bring it up to you? Like what was that conversation like?

Maria:

When I went to his checkup, the doctor mentioned me HEMLIBRA. That will be a really good therapy for Carlos since we were still having to do infusions, you know, even though we had the prophylaxis and were still having the bleeds.

ON SCREEN:

HEMLIBRA is a prophylactic treatment. HEMLIBRA is for routine prophylaxis use only. Do not use HEMLIBRA to treat a breakthrough bleed. HCPs will provide instructions regarding when to use an on-demand bypassing agent or factor VIII (FVIII) and the recommended dose and schedule to use for breakthrough bleed treatment.

Maria:

Once he explained to me that, you know, that, how the prophylaxis will work for him, every 2 weeks, that was really excitement because the process of the prophylaxis.

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.

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.

Dr. Tami Singleton:

And so, after you've provided that education for those patients, when you see them and kind of short follow up after a switch or a change to HEMLIBRA, what kinds of things are different?

ON SCREEN:

Experience With HEMLIBRA

Dr. Erin Cockrell:

They're doing well, they're having very few to maybe no treated bleeds.

ON SCREEN:

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.

Maya Bloomberg:

So I can give you countless examples where this has happened, where I’ll have a patient tell me that he's well-controlled, only having a couple bleeds a year, but once switching to HEMLIBRA, they'll realize how much control they're having over their bleeding symptoms and reporting not having to use any factor replacement in the past 6 months.

ON SCREEN:

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

Maya Bloomberg:

So I think the ease of administration is wonderful, but ultimately the efficacy ends. My real-world experience speaks even more volumes for why somebody should consider switching to HEMLIBRA.

Dr. Tami Singleton:

When you think about Carlos, the change that you've seen with the switch, how would you describe that?

ON SCREEN:

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

Maria:

We haven't had to do any bleeds with factor in 6 months. And like I say, sometimes I help him to push the medicine.

ON SCREEN:

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

Maria:

Sometimes he says, I will do it mom with my supervision and we're ready to go.

Dr. Tami Singleton:

How have your experiences over time with HEMLIBRA had an impact or changed, or sort of refocused your prescribing HEMLIBRA as a treatment option?

ON SCREEN:

Continuing to Evolve

Maya Bloomberg:

So I think with the more time that I'm able to use HEMLIBRA, my impression of it is getting better and better.

ON SCREEN:

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

Dr. Erin Cockrell:

Because, you know, we get further and further into any newer product, there's a comfort level that comes with that. Obviously, as we have more and more patients on it, we still have a lot to learn. But now that we've had it available for as long as it's been out, then we've developed that comfort level with it.

Dr. Tami Singleton:

There are a lot of layers to this question. First, we discovered that there's no real definition of well-controlled. While some may say a few treated bleeds a year is okay, a parent may feel that every single bleed or every single infusion is a very big deal.

ON SCREEN:

Why would I bring up switching to a patient who is well-controlled on factor?

Dr. Tami Singleton:

So to answer the question we set out for, why switch a patient who's well-controlled and hasn't asked to switch?

ON SCREEN:

  • Not all patients or caregivers will ask for a switch
  • HEMLIBRA may improve their overall management of hemophilia A through:
    • Subcutaneous administration
    • Flexible dosing options

Dr. Tami Singleton:

Not all patients or parents are going to ask for a switch, especially if they think they're doing well enough, but if they're not doing as well as they think they are, HEMLIBRA may be able to have an impact on their overall management of their disease.

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.

VO:

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 greater than 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, 3 out of 391, and thrombotic events were reported in 0.5% of patients, 2 out of 391. In patients who received at least 1 dose of aPCC, TMA was reported in 8.1% of patients, 3 out of 37 and thrombotic events were reported in 5.4% of patients, 2 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. 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.

VO:

Immunogenicity. Treatment with HEMLIBRA may induce anti-drug antibodies. Anti-emicizumab-kxwh antibodies were reported in 5.1% of patients (34/668) treated with HEMLIBRA in clinical trials. Most patients with anti-emicizumab-kxwh antibodies did not experience a change in HEMLIBRA plasma concentrations or an increase in bleeding events; however, in uncommon cases (incidence <1%), the presence of neutralizing antibodies with decreasing plasma concentration may be associated with loss of efficacy.

Monitor for clinical signs of loss of efficacy (eg, increase in breakthrough bleeding events) and if observed, promptly assess the etiology and consider a change in treatment if neutralizing anti-emicizumab-kxwh antibodies are suspected.

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:

Most common adverse reactions. The most common adverse reactions incidence greater than or equal to 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 greater than 100 units per kilogram per 24 hours of aPCC for 24 hours or more. Two 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.

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 or injection site erythema, 11%, injection site pruritis, 4%, and injection site pain, 4%.

VO:

Other less common, less than 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.

VO:

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.

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.

ABR=annualized bleed rate; CI=confidence interval; FVIII=factor VIII; IQR=interquartile range; QW=once weekly; Q2W=once every 2 weeks; Q4W=once every 4 weeks.

Doctor Discussion Guide

Help you determine whether HEMLIBRA is right for your patient.

HEMLIBRA Side Effects

Learn more about the side effects associated with HEMLIBRA.

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.

Immunogenicity
Treatment with HEMLIBRA may induce anti-drug antibodies. Anti-emicizumab-kxwh antibodies were reported in 5.1% of patients (34/668) treated with HEMLIBRA in clinical trials. Most patients with anti-emicizumab-kxwh antibodies did not experience a change in HEMLIBRA plasma concentrations or an increase in bleeding events; however, in uncommon cases (incidence <1%), the presence of neutralizing antibodies with decreasing plasma concentration may be associated with loss of efficacy.

Monitor for clinical signs of loss of efficacy (eg, increase in breakthrough bleeding events) and if observed, promptly assess the etiology and consider a change in treatment if neutralizing anti-emicizumab-kxwh antibodies are suspected.

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.

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