First new medicine in nearly 20 years to treat people with
hemophilia A with inhibitors
HEMLIBRA substantially reduced bleeds in adults and children
Only medicine that can be self-administered once weekly by
injection under the skin (subcutaneously)
SOUTH SAN FRANCISCO, Calif.(BUSINESS WIRE)
Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY),
announced today that the U.S. Food and Drug Administration (FDA) has
approved HEMLIBRA (emicizumab-kxwh) for routine
prophylaxis to prevent or reduce the frequency of bleeding episodes in
adults and children with hemophilia A with factor VIII inhibitors.
Nearly one in three people with severe hemophilia A can develop
inhibitors to factor VIII replacement therapies, putting them at greater
risk for life-threatening bleeds or repeated bleeds that can cause
long-term joint damage. In two of the largest pivotal clinical studies
for people with hemophilia A with inhibitors, HEMLIBRA was shown to
substantially reduce bleeds in adults and children.
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People with hemophilia A who develop inhibitors face significant
challenges preventing bleeds and typically require infusions of medicine
multiple times a week, which can be especially difficult for young
children and their families, said Guy Young, M.D., director of
Hemostasis and Thrombosis Program, Children's Hospital Los Angeles, and
professor of Pediatrics, University of Southern California Keck School
of Medicine, Los Angeles, California. This new medicine has been shown
to reduce the frequency of bleeds compared to the currently available
medicines and only needs to be injected once a week. This could make a
meaningful difference for these children.
Before HEMLIBRA, my 7-year-old son needed intravenous infusions that
could take up to two hours at least three times a week, so our lives
revolved around his treatment, said Amber Hill, mother of a young boy
with hemophilia A with inhibitors. With HEMLIBRA, he now has an
injection once a week that he has proudly learned to administer himself
to help prevent bleeds. Not only has he had fewer bleeds compared to his
prior treatment, he has more time to be a kid and we have more quality
time as a family because of the new treatment schedule.
In the Phase III HAVEN 1 study, people 12 years of age or older with
hemophilia A with inhibitors who received HEMLIBRA prophylaxis had a
statistically significant reduction in treated bleeds of 87 percent (95
percent CI: 72.3; 94.3, p<0.0001) compared to those who received no
prophylaxis. In a first-of-its-kind intra-patient analysis, HEMLIBRA
prophylaxis resulted in a statistically significant reduction in treated
bleeds of 79 percent (95 percent CI: 51.4; 91.1, p=0.0003) compared to
previous treatment with bypassing agent (BPA) prophylaxis collected in a
non-interventional study (NIS) prior to enrollment.
Interim results from the pivotal HAVEN 2 study in children younger than
12 years of age with hemophilia A with inhibitors showed that 87 percent
(95 percent CI: 66.4; 97.2) of children who received HEMLIBRA
prophylaxis experienced zero treated bleeds.In an intra-patient
analysis of 13 children who had participated in the NIS, HEMLIBRA
prophylaxis resulted in a 99 percent reduction in treated bleeds
compared to previous treatment with a BPA either as prophylaxis (n=12)
or on-demand (n=1). The most common adverse events (AEs) occurring in 10
percent or more of people treated with HEMLIBRA in pooled studies were
injection site reactions, headache and joint pain (arthralgia).
Today's approval of HEMLIBRA represents an important advancement for
people with hemophilia A with inhibitors, who have struggled to manage
their bleeding disorder and havent had a new medicine in nearly 20
years, said Sandra Horning, M.D., chief medical officer and head of
Global Product Development. We believe HEMLIBRA will improve protection
against bleeds and reduce the treatment administration burden for people
with hemophilia A with inhibitors, and we are committed to helping them
access this medicine.
HEMLIBRA will be available to people in the U.S. shortly after approval.
Genentech is committed to helping people with hemophilia A with
inhibitors access HEMLIBRA and will be offering comprehensive services
to help minimize barriers to access and reimbursement. Patients can call
(866) HEMLIBRA (436-5427) for more information. For people who qualify,
Genentech also plans to offer patient assistance programs through
Genentech Access Solutions. More information is available at (866)
4ACCESS/(866) 422-2377 or http://www.Genentech-Access.com.
HEMLIBRA was reviewed by the FDA under Priority Review and granted
Breakthrough Therapy Designation by the FDA in people 12 years of age or
older with hemophilia A with inhibitors in September 2015. Data from
HAVEN 1 and HAVEN 2 are being reviewed under accelerated assessment by
the European Medicines Agency (EMA) and submissions to health
authorities around the world are ongoing.
HEMLIBRA is being studied in a robust clinical development program that
includes two additional Phase III studies. HAVEN 3 is evaluating
HEMLIBRA prophylaxis dosed once weekly or once every other week in
people 12 years of age or older with hemophilia A without inhibitors to
factor VIII. HAVEN 4 is evaluating HEMLIBRA prophylaxis dosed every four
weeks in people 12 years of age or older with hemophilia A with or
About HAVEN 1 (NCT02622321)
HAVEN 1 is a randomized, multicenter, open-label, Phase III study
evaluating the efficacy, safety and pharmacokinetics of once-weekly
subcutaneous administration of HEMLIBRA prophylaxis compared to no
prophylaxis in adults and adolescents with hemophilia A with inhibitors
to factor VIII. The study included 109 patients (12 years of age and
older) with hemophilia A with inhibitors to factor VIII, who were
previously treated with BPAs on-demand or as prophylaxis. Patients
previously treated with on-demand BPAs were randomized in a 2:1 ratio to
receive HEMLIBRA prophylaxis (Arm A) or no prophylaxis (Arm B). Patients
previously treated with BPAs as prophylaxis received HEMLIBRA
prophylaxis (Arm C). Additional patients previously treated with
on-demand BPAs were also enrolled in a separate arm (Arm D). On-demand
treatment of breakthrough bleeds with BPAs was allowed per protocol in
Below is a summary of key data from the HAVEN 1 study.
The primary endpoint showed a statistically significant reduction in
treated bleeds of 87 percent (95 percent CI: 72.3; 94.3, p<0.0001)
with HEMLIBRA prophylaxis compared to no prophylaxis.
In addition, 62.9 percent (95 percent CI: 44.9; 78.5) of patients
who received HEMLIBRA prophylaxis experienced zero treated bleeds
compared to 5.6 percent (95 percent CI: 0.1; 27.3) of patients who
received no prophylaxis.
All 12 secondary endpoints were positive. In a first-of-its-kind
intra-patient analysis, HEMLIBRA prophylaxis resulted in a
statistically significant reduction in treated bleeds of 79 percent
(95 percent CI: 51.4; 91.1, p=0.0003) compared to previous treatment
with BPA prophylaxis collected in the NIS prior to enrollment.
Additionally, 70.8 percent (95 percent CI: 48.9; 87.4) of patients
experienced zero treated bleeds with HEMLIBRA prophylaxis compared to
12.5 percent (95 percent CI: 2.7; 32.4) with previous treatment with
BPA prophylaxis during the NIS.
Improvements in bleed rate with HEMLIBRA prophylaxis compared to no
prophylaxis included an 80 percent (95 percent CI: 62.5; 89.8,
p<0.0001) reduction in all bleeds, a 92 percent (95 percent CI: 84.6;
96.3, p<0.0001) reduction in treated spontaneous bleeds, an 89 percent
(95 percent CI: 48; 97.5, p=0.0050) reduction in treated joint bleeds
and a 95 percent (95 percent CI: 77.3; 99.1, p=0.0002) reduction in
treated target joint bleeds.
An improvement in Physical Health Score of the Haemophilia-specific
Quality of Life (Haem-A-QoL) questionnaire was observed with HEMLIBRA
prophylaxis compared to no prophylaxis. This was measured at 25 weeks
in adults 18 years of age and older and evaluated hemophilia-related
symptoms (painful swellings and presence of joint pain) and physical
function (pain with movement and difficulty walking far).
HEMLIBRA may cause serious side effects when used with aPCC (FEIBA),
including thrombotic microangiopathy (TMA) and blood clots (thrombotic
events). Cases of thrombotic microangiopathy and thrombotic events were
reported when on average a cumulative amount of >100 U/kg/24 hours of
activated prothrombin complex concentrate (aPCC) was administered for 24
hours or more to patients receiving HEMLIBRA prophylaxis. As previously
reported, three people experienced TMA events and two people experienced
serious thrombotic events in the HAVEN 1 study.
About HAVEN 2 (NCT02795767)
HAVEN 2 is a single-arm, multicenter, open-label, clinical study in
children younger than 12 years of age with hemophilia A with inhibitors
to factor VIII. The study is evaluating the efficacy, safety and
pharmacokinetics of once-weekly subcutaneous administration of HEMLIBRA
prophylaxis. The interim efficacy analysis, after at least 12 weeks of
treatment, included 23 children.
After a median observation time of 38.1 weeks, the interim analysis
showed that 87 percent (95 percent CI: 66.4; 97.2) of children who
received HEMLIBRA prophylaxis experienced zero treated bleeds. Interim
data also showed:
34.8 percent (95 percent CI: 16.4; 57.3) of children experienced
zero bleeds overall, which includes all treated and non-treated
95.7 percent (95 percent CI: 78.1; 99.9) of children experienced
zero treated spontaneous bleeds.
95.7 percent (95 percent CI: 78.1; 99.9) of children experienced
zero treated joint bleeds.
100 percent (95 percent CI: 85.2; 100) of children experienced
zero treated target joint bleeds.
In an intra-patient analysis, 13 children who had participated in the
NIS had an annualized bleeding rate (ABR) for treated bleeds of 17.2
(95 percent CI: 12.4; 23.8) on previous treatment with a BPA either as
prophylaxis (n=12) or on-demand (n=1) compared to 0.2 (95 percent CI:
0.1; 0.8) on HEMLIBRA prophylaxis, corresponding to a 99 percent
reduction in bleed rate. On HEMLIBRA prophylaxis, 11 children (84.6
percent) experienced zero treated bleeds.
The most common AEs occurring in 10 percent or more of people treated
with HEMLIBRA in pooled studies were injection site reactions, headache
and joint pain (arthralgia).
HEMLIBRA is a bispecific factor IXa- and factor X-directed antibody. It
is designed to bring together factor IXa and factor X, proteins required
to activate the natural coagulation cascade and restore the blood
clotting process for hemophilia A patients. HEMLIBRA is a prophylactic
(preventative) treatment that can be administered by an injection of a
ready-to-use solution under the skin (subcutaneously) once weekly.
HEMLIBRA was created by Chugai Pharmaceutical Co., Ltd. and is being
co-developed by Chugai, Roche and Genentech.
HEMLIBRA U.S. Indication
HEMLIBRA is a prescription medicine used for routine prophylaxis to
prevent or reduce the frequency of bleeding episodes in adults and
children with hemophiliaA with factor VIII inhibitors.
Important Safety Information
What is the most important information to know about HEMLIBRA?
HEMLIBRA increases the potential for blood to clot. Discontinue
prophylactic use of bypassing agents the day before starting HEMLIBRA
prophylaxis. Carefully follow the healthcare provider's
instructions regarding when to use an on-demand bypassing agent, and the
dose and schedule one should use.
HEMLIBRA may cause the following serious side effects when used with
aPCC (FEIBA), including:
Thrombotic microangiopathy (TMA). This is a condition involving
blood clots and injury to small blood vessels that may cause harm to
one's kidneys, brain, and other organs. Patients should get medical
help right away if they have any of the following signs or symptoms
during or after treatment with HEMLIBRA:
swelling of arms and legs
yellowing of skin and eyes
stomach (abdomen) or back pain
nausea or vomiting
Blood clots (thrombotic events). Blood clots may form in blood
vessels in one's arm, leg, lung or head. Patients should get medical
help right away if they have any of these signs or symptoms of blood
clots during or after treatment with HEMLIBRA:
swelling in arms or legs
pain or redness in the arms or legs
shortness of breath
chest pain or tightness
fast heart rate
cough up blood
numbness in the face
eye pain or swelling
If aPCC (FEIBA) is needed, patients should
talk to their healthcare provider in case they feel they need more than
100 U/kg of aPCC (FEIBA) total.
How should patients use HEMLIBRA?
HEMLIBRA may interfere with laboratory tests that measure how well blood
is clotting and may cause a false reading. Patients should talk to their
healthcare provider about how this may affect their care.
What are the other possible side effects of HEMLIBRA?
The most common side effects of HEMLIBRA include: redness,
tenderness, warmth, or itching at the site of injection; headache; and
These are not all of the possible side effects of HEMLIBRA. Patients
should call their doctor for medical advice about side effects.
Side effects may be reported to the FDA at (800) FDA-1088 or http://www.fda.gov/medwatch.
Side effects may also be reported to Genentech at (888) 835-2555.
Please see the HEMLIBRA full Prescribing
Information and the Medication
Guide, including Serious Side Effects, for more important
About hemophilia A with inhibitors
Hemophilia A is an inherited, serious disorder in which a person's blood
does not clot properly, leading to uncontrolled and often spontaneous
bleeding. Hemophilia affects around 20,000 people in the United States,
with hemophilia A being the most common form and approximately 50-60
percent of people living with a severe form of the disorder.
People with hemophilia A either lack or do not have enough of a clotting
protein called factor VIII. In a healthy person, when a bleed occurs,
factor VIII brings together the clotting factors IXa and X, which is a
critical step in the formation of a blood clot to help stop bleeding.
Depending on the severity of their disorder, people with hemophilia A
can bleed frequently, especially into their joints or muscles. These
bleeds can present a significant health concern as they often cause pain
and can lead to chronic swelling, deformity, reduced mobility and
long-term joint damage.
A serious complication of treatment is the development of inhibitors to
factor VIII replacement therapies. Inhibitors are antibodies developed
by the body's immune system that bind to and block the efficacy of
replacement factor VIII, making it difficult, if not impossible, to
obtain a level of factor VIII sufficient to control bleeding. Most
people with hemophilia A who develop inhibitors typically infuse BPA
therapies, either on-demand (episodic) or as prophylaxis.
About Genentech in hemophilia
In 1984, Genentech scientists were the first to clone recombinant factor
VIII in response to the contaminated hemophilia blood supply crisis of
the early 1980s. For more than 20 years, Genentech has been developing
medicines to bring innovative treatment options to people with diseases
of the blood within oncology, and in hemophilia A. Genentech is
committed to improving treatment and care in the hemophilia community by
delivering meaningful science and clinical expertise. For more
information visit http://www.gene.com/hemophilia.
Founded more than 40 years ago, Genentech is a leading biotechnology
company that discovers, develops, manufactures and commercializes
medicines to treat patients with serious or life-threatening medical
conditions. The company, a member of the Roche Group, has headquarters
in South San Francisco, California. For additional information about the
company, please visit http://www.gene.com.
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Liz Walmsley, 650-467-6800
Sonali Chopra, 650-467-0842
Karl Mahler, 011 41 61 687 8503