Market Overview

FDA Grants Priority Review to Genentech's HEMLIBRA (emicizumab-kxwh) for People with Hemophilia A without Factor VIII Inhibitors

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Genentech, a member of the Roche Group ((SIX: RO, ROG, OTCQX:RHHBY),
announced today that the U.S. Food and Drug Administration (FDA) has
accepted the company's supplemental Biologics License Application (sBLA)
and granted Priority Review for HEMLIBRA® (emicizumab-kxwh)
for adults and children with hemophilia A without factor VIII
inhibitors. The sBLA is based on data from the Phase III HAVEN 3 study.
The FDA is expected to make a decision on approval by October 4, 2018.

"People with hemophilia A can face significant challenges in managing
their condition and may need to adapt their daily lives to avoid bleeds
and accommodate treatment," said Sandra Horning, M.D., chief medical
officer and head of Global Product Development. "We believe the FDA's
decision to grant Priority Review to HEMLIBRA underscores its potential
to improve the standard of care for people without factor VIII
inhibitors and to help reduce treatment burden by offering more flexible
subcutaneous dosing options. We look forward to working with the FDA to
hopefully bring HEMLIBRA to all people with hemophilia A as quickly as
possible."

In the HAVEN 3 study, adults and adolescents aged 12 years or older with
hemophilia A without factor VIII inhibitors who received HEMLIBRA
prophylaxis every week or every two weeks showed a 96 percent (p<0.0001)
and 97 percent (p<0.0001) reduction in treated bleeds, respectively,
compared to those who received no prophylaxis. In an additional arm of
the study, people who had previously received factor VIII prophylaxis in
a non-interventional study switched to HEMLIBRA prophylaxis, allowing
for an intra-patient comparison of two prophylaxis regimens. Based on
the intra-patient comparison, HEMLIBRA demonstrated a statistically
significant reduction of 68 percent (p<0.0001) in treated bleeds, making
it the first medicine to show superior efficacy to prior treatment with
factor VIII prophylaxis, the 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 in the
HAVEN 3 study were injection site reactions, joint pain (arthralgia),
common cold symptoms (nasopharyngitis), headache, upper respiratory
tract infection and influenza. Results from the HAVEN 3 study were
presented at the World Federation of Hemophilia (WFH) 2018 World
Congress in May.

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. The FDA
granted Breakthrough Therapy Designation for HEMLIBRA in people with
hemophilia A without factor VIII inhibitors in April 2018 based on data
from the HAVEN 3 study. 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. Data from
the HAVEN 3 study have also been submitted for approval consideration to
the European Medicines Agency. Submissions to other regulatory
authorities around the world are ongoing.

HEMLIBRA 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. HEMLIBRA was also
recently approved by regulatory authorities in other countries around
the world, including by the European Commission in February 2018 for
routine prophylaxis of bleeding episodes in people with hemophilia A
with factor VIII inhibitors.

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
until the end of study (Arm A), subcutaneous HEMLIBRA prophylaxis at 3
mg/kg/wk for 4 weeks, followed by 3 mg/kg/2wks for at least 24 weeks
(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.

In the Phase III HAVEN 3 study, adults and adolescents aged 12 years or
older without factor VIII inhibitors who received HEMLIBRA prophylaxis
every week or every two weeks showed a 96 percent (p<0.0001) and 97
percent (p<0.0001) reduction in treated bleeds, respectively, compared
to those who received no prophylaxis. In addition, 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.
Importantly, in an intra-patient comparison in patients who were
previously enrolled in a prospective non-interventional study (NIS),
once-weekly HEMLIBRA prophylaxis showed superior efficacy compared to
prior factor VIII prophylaxis, the standard of care for people with
hemophilia A without factor VIII inhibitors, as demonstrated by a 68
percent reduction (p<0.0001) in treated bleeds.

There were no unexpected or serious adverse events (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
in the HAVEN 3 study 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 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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