Market Overview

Positive Phase III Results for Genentech's HEMLIBRA (emicizumab-kxwh) for Hemophilia A Without Factor VIII Inhibitors Published in New England Journal of Medicine

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– HEMLIBRA prophylaxis significantly reduced bleeds compared to no
prophylaxis –

– HEMLIBRA is the first medicine to demonstrate superior efficacy to
prior factor VIII prophylaxis based on a statistically significant
reduction in treated bleeds in an intra-patient comparison –

– HEMLIBRA is currently under Priority Review by the FDA for people
with hemophilia A without factor VIII inhibitors –

Genentech, a member of the Roche Group ((SIX: RO, ROG, OTCQX:RHHBY),
announced today that pivotal data from the Phase III HAVEN 3 study,
which evaluated HEMLIBRA® (emicizumab-kxwh) prophylaxis
administered every week or every two weeks in adults and adolescents
aged 12 years or older with hemophilia A without factor VIII inhibitors,
were published in the August 30, 2018, issue of the New England
Journal of Medicine
(NEJM).

"In the HAVEN 3 study, HEMLIBRA showed a significant and clinically
meaningful reduction in bleeds in people with hemophilia A without
factor VIII inhibitors, while offering multiple subcutaneous dosing
options," said Dr. Johnny Mahlangu, Faculty of Health Sciences,
University of the Witwatersrand and NHLS, Johannesburg, South Africa.
"The publication of these results in the New England Journal of
Medicine
represents a major advance for hemophilia research and
reinforces the potential of HEMLIBRA to change the standard of care for
people with hemophilia A."

"Current prophylactic treatment options for people with hemophilia A can
require frequent intravenous infusions, and despite treatment, many
continue to have bleeds that can lead to long-term joint damage," said
Sandra Horning, M.D., chief medical officer and head of Global Product
Development. "Given the challenges many people face managing their
hemophilia, we believe HEMLIBRA could make a meaningful difference, and
we are working with health authorities to hopefully make this treatment
available to people with hemophilia A without factor VIII inhibitors as
soon as possible."

Data from the HAVEN 3 study showed that HEMLIBRA prophylaxis
administered subcutaneously every week or every two weeks significantly
reduced treated bleeds by 96 percent (rate ratio [RR]=0.04; p<0.0001)
and 97 percent (RR=0.03; p<0.0001), respectively, compared to no
prophylaxis. Results also showed that 55.6 percent (95 percent CI: 38.1;
72.1) of people treated with HEMLIBRA every week and 60 percent (95
percent CI: 42.1; 76.1) of people treated with HEMLIBRA every two weeks
experienced zero treated bleeds, compared to 0 percent (95 percent CI:
0.0; 18.5) of people treated with no prophylaxis. In an intra-patient
comparison of people who previously received factor VIII prophylaxis in
a prospective non-interventional study and switched to HEMLIBRA
prophylaxis, HEMLIBRA demonstrated a statistically significant reduction
of 68 percent (RR=0.32; p<0.0001) in treated bleeds, making it the first
medicine to show superior efficacy to prior factor VIII prophylaxis
treatment, the current standard of care. There were no unexpected or
serious adverse events (AEs) related to HEMLIBRA in the HAVEN 3 study,
and the most common AEs were consistent with previous studies. The most
common AEs occurring in 5 percent or more of people were injection site
reactions, joint pain (arthralgia), common cold symptoms
(nasopharyngitis), headache, upper respiratory tract infection and
influenza.

Earlier this year, the U.S. Food and Drug Administration (FDA) granted
Breakthrough Therapy Designation and Priority Review to HEMLIBRA for
people with hemophilia A without factor VIII inhibitors based on data
from the HAVEN 3 study. The FDA is expected to make a decision on
approval by October 4, 2018. Breakthrough Therapy Designation is
designed to expedite the development and review of medicines intended to
treat a serious condition with preliminary evidence that indicates they
may demonstrate substantial improvement over existing therapies.
Priority Review designation is granted to medicines that the FDA has
determined to have the potential to provide significant improvements in
the treatment, prevention or diagnosis of a serious disease. Submissions
to other regulatory authorities around the world are ongoing.

About HAVEN 3 (NCT02847637)

HAVEN 3 is a randomized, multicenter, open-label, Phase III study
evaluating the efficacy, safety and pharmacokinetics of HEMLIBRA
prophylaxis versus no prophylaxis (episodic/on-demand factor VIII
treatment) in people with hemophilia A without factor VIII inhibitors.
The study included 152 patients with hemophilia A (12 years of age or
older) who were previously treated with factor VIII therapy either
on-demand or for prophylaxis. Patients previously treated with on-demand
factor VIII were randomized in a 2:2:1 fashion to receive subcutaneous
HEMLIBRA prophylaxis at 3 mg/kg/wk for 4 weeks, followed by 1.5 mg/kg/wk
for at least 24 weeks (Arm A), subcutaneous HEMLIBRA prophylaxis at 3
mg/kg/wk for 4 weeks, followed by 3 mg/kg/2wks (Arm B) for at least 24
weeks or no prophylaxis (Arm C) for at least 24 weeks. Patients
previously treated with factor VIII prophylaxis received subcutaneous
HEMLIBRA prophylaxis at 3 mg/kg/wk for 4 weeks, followed by 1.5 mg/kg/wk
until the end of study (Arm D). Episodic treatment of breakthrough
bleeds with factor VIII therapy was allowed per protocol.

The Phase III HAVEN 3 study in people with hemophilia A without factor
VIII inhibitors met its primary endpoint and key secondary endpoints.
Data from the study showed:

  • HEMLIBRA prophylaxis every week or every two weeks resulted in a 96
    percent (RR=0.04; p<0.0001) and 97 percent (RR=0.03; p<0.0001)
    reduction in treated bleeds, respectively, compared to no prophylaxis.
  • 55.6 percent (95 percent CI: 38.1, 72.1) of people treated with
    HEMLIBRA every week and 60 percent (95 percent CI: 42.1, 76.1) of
    people treated with HEMLIBRA every two weeks experienced zero treated
    bleeds, compared to 0 percent (95 percent CI: 0.0; 18.5) of people
    treated with no prophylaxis.
  • 91.7 percent (95 percent CI: 77.5, 98.2) of people treated with
    HEMLIBRA prophylaxis every week and 94.3 percent (95 percent CI: 80.8,
    99.3) of people treated with HEMLIBRA prophylaxis every two weeks
    experienced three or fewer treated bleeds, compared to 5.6 percent (95
    percent CI: 0.1, 27.3) of people treated with no prophylaxis.
  • HEMLIBRA prophylaxis every week or every two weeks resulted in a 95
    percent (RR=0.05; p<0.0001) and 95 percent (RR=0.05; p<0.0001)
    reduction in treated target-joint bleeds, respectively, compared to no
    prophylaxis.
  • HEMLIBRA prophylaxis every week or every two weeks resulted in a 95
    percent (RR=0.05; p<0.0001) and 94 percent (RR=0.06; p<0.0001)
    reduction in all bleeds, respectively, compared to no prophylaxis.
  • HEMLIBRA prophylaxis every week demonstrated a statistically
    significant reduction of 68 percent (RR=0.32; p<0.0001) in treated
    bleeds compared to prior factor VIII prophylaxis based on an
    intra-patient comparison of people who were previously enrolled in a
    prospective non-interventional study.
  • There were no unexpected or serious AEs related to HEMLIBRA, and the
    most common AEs were consistent with previous studies. No thrombotic
    events or cases of thrombotic microangiopathy were observed. The most
    common AEs occurring in 5 percent or more of people were injection
    site reactions, joint pain (arthralgia), common cold symptoms
    (nasopharyngitis), headache, upper respiratory tract infection and
    influenza.

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 globally 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. 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.

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.

Before using HEMLIBRA, patients should tell their healthcare provider
about all of their medical conditions, including if they:

  • are pregnant or plan to become pregnant. It is not known if HEMLIBRA
    may harm an unborn baby. Females who are able to become pregnant
    should use birth control (contraception) during treatment with
    HEMLIBRA.
  • are breastfeeding or plan to breastfeed. It is not known if HEMLIBRA
    passes into breast milk.

What should patients know about lab monitoring?

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.

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

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.

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 and 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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