Market Overview

FDA Grants Breakthrough Therapy Designation for Genentech's HEMLIBRA (emicizumab-kxwh) in Hemophilia a Without Inhibitors

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– Designation based on Phase III HAVEN 3 study demonstrating HEMLIBRA
prophylaxis significantly reduced bleeds compared to no prophylaxis –

– First medicine to show superior efficacy compared to prior factor
VIII prophylaxis in an intra-patient comparison –

Genentech, a member of the Roche Group ((SIX: RO, ROG, OTCQX:RHHBY),
announced today that the U.S. Food and Drug Administration (FDA) has
granted Breakthrough Therapy Designation to HEMLIBRA®
(emicizumab-kxwh) for people with hemophilia A without factor VIII
inhibitors. Breakthrough Therapy Designation is designed to accelerate
the development and review of medicines intended to treat a serious
condition with preliminary evidence that indicates they may demonstrate
a substantial improvement over existing therapies.

"HEMLIBRA is the first medicine to show superior efficacy compared to
factor VIII prophylaxis, the standard of care for people with hemophilia
A without inhibitors, in an intra-patient comparison," said Sandra
Horning, M.D., chief medical officer and head of Global Product
Development. "We look forward to working with health authorities to make
HEMLIBRA available to people without inhibitors as soon as possible, and
we are excited to share this news with the community as we join in
celebrating World Hemophilia Day."

This designation is based on data from the Phase III HAVEN 3 study in
people 12 years or older with hemophilia A without inhibitors. In the
study, HEMLIBRA prophylaxis dosed subcutaneously every week or every two
weeks showed a statistically significant and clinically meaningful
reduction in treated bleeds compared to no prophylaxis. In an
intra-patient comparison, once-weekly HEMLIBRA prophylaxis was superior
to prior factor VIII prophylaxis as demonstrated by a statistically
significant and clinically meaningful reduction in treated bleeds. The
most common adverse events with HEMLIBRA were injection site reactions,
and no new safety signals were observed. No thrombotic microangiopathy
or thrombotic events occurred in this study.

HEMLIBRA was granted its first Breakthrough Therapy Designation in
September 2015 and was approved by the FDA in November 2017 for routine
prophylaxis to prevent or reduce the frequency of bleeding episodes in
adults and children with hemophilia A with factor VIII inhibitors based
on results from the HAVEN 1 and HAVEN 2 studies.

The HEMLIBRA development program reflects Genentech's commitment to
address clinical unmet needs in the hemophilia A community. Roche and
Genentech are proud to support the World Federation of Hemophilia and
the global bleeding disorders community as sponsors of World Hemophilia
Day. To learn more about World Hemophilia Day and the World Federation
of Hemophilia visit http://www.wfh.org/en/whd.

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 inhibitors to factor
VIII. 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
until the end of study (Arm A), subcutaneous HEMLIBRA prophylaxis at 3
mg/kg/wk for 4 weeks, followed by 3 mg/kg/2wks until the end of study
(Arm B), or no prophylaxis (Arm C). 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.

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

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.

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.

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 their 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 a female's breast milk.

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 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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