FDA Approves Genentech’s HEMLIBRA (emicizumab-kxwh) for Hemophilia A with Inhibitors
– 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)
–
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 haven’t 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 without inhibitors.
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 all arms.
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 bleeds.
- 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).
About HEMLIBRA
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 hemophilia A 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:
- confusion
- weakness
- swelling of arms and legs
- yellowing of skin and eyes
- stomach (abdomen) or back pain
- nausea or vomiting
- feeling sick
- decreased urination
-
Blood clots (thrombotic events). Blood clots may form in blood vessels in 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
- feel faint
- headache
- numbness in the face
- eye pain or swelling
- trouble seeing
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 joint pain.
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 safety information.
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.
About Genentech
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.
for Genentech
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