- This historic approval provides a new treatment option
that reduces the rate of annual bleeds, reduces or eliminates the
need for prophylactic therapy and generates elevated and sustained
factor IX levels for years after a one-time infusion
- With the approval of HEMGENIX, CSL now offers an even
more comprehensive portfolio of treatments for people living with
hemophilia B, ushering in a new era of treatment options
KING OF
PRUSSIA, Pa., Nov. 22,
2022 /PRNewswire/ -- Global biotechnology leader CSL
(ASX: CSL) today announced that the U.S. Food and Drug
Administration (FDA) approved HEMGENIX® (etranacogene
dezaparvovec-drlb), the first and only one-time gene therapy for
appropriate adults with hemophilia B. HEMGENIX is approved for the
treatment of adults with hemophilia B who currently use factor IX
prophylaxis therapy, or have current or historical life-threatening
hemorrhage or have repeated, serious spontaneous bleeding episodes.
In the ongoing clinical trial, HEMGENIX reduced the rate of annual
bleeds and 94 percent of patients discontinued factor IX
prophylaxis and remained prophylaxis-free.
Experience the full interactive Multichannel News Release here:
https://www.multivu.com/players/English/9088951-csl-announces-fda-approval-of-hemgenix/
"As part of our promise to patients, CSL is committed to
delivering innovative and groundbreaking solutions to address unmet
medical needs, and we are proud to introduce the next wave of
breakthrough medicines for people living with hemophilia B," said
Paul Perreault, CSL's Chief
Executive Officer and Managing Director. "We recognize and thank
all trial participants, scientists and investigators—without whom
this important achievement would not have been possible—and look
forward to seeing the positive impact of HEMGENIX on the hemophilia
B community."
Hemophilia B is a rare, lifelong bleeding disorder caused by a
single gene defect, resulting in insufficient production of factor
IX, a protein primarily produced by the liver that helps blood
clots form. Treatments for moderate to severe hemophilia B include
prophylactic infusions of factor IX replacement therapy to
temporarily replace or supplement low levels of blood-clotting
factor and, while these therapies are effective, those with
hemophilia B must adhere to strict, lifelong infusion schedules.
They may also still experience spontaneous bleeding episodes as
well as limited mobility, joint damage or severe pain as a result
of the disease. For appropriate patients, HEMGENIX allows people
living with hemophilia B to produce their own factor IX, which can
lower the risk of bleeding.
"We are thrilled to witness this milestone in hemophilia B
treatment," shared Kim Phelan, Chief
Operating Officer of The Coalition for Hemophilia B. "Over the
years we have seen a variety of advancements for the hemophilia
community, but gene therapy is the first treatment option to offer
those living with hemophilia B--and caregivers--the possibility of
freedom from the need for regular, ongoing infusions."
The FDA approval is supported by results from the ongoing HOPE-B
trial, the largest gene therapy trial in hemophilia B to date.
Results from the study demonstrated that HEMGENIX allowed patients
to produce mean factor IX activity of 39 percent at six months and
36.7 percent at 24 months post infusion. Seven to 18 months
post-infusion, the mean adjusted annualized bleeding rate (ABR) for
all bleeds was reduced by 54 percent compared to the six-month
lead-in period on factor IX prophylactic replacement therapy
(4.1 to 1.9). In addition, 94 percent (51 out of 54) of patients
treated with HEMGENIX discontinued use of prophylaxis and remained
free of previous continuous routine prophylaxis therapy. The most
common side effects (incidence ≥5%) were liver enzyme elevations,
headache, elevated levels of a certain blood enzyme, flu-like
symptoms, infusion-related reactions, fatigue, nausea and feeling
unwell.
"HEMGENIX is unique in its approach to increasing mean factor IX
activity and hemostatic protection in those with hemophilia B, and
today's approval could fundamentally transform the treatment
paradigm for this life-long condition," said Dr. Steven Pipe, Professor and the Laurence A. Boxer
Research Professor of Pediatrics and Professor of Pathology at the
University of Michigan and a lead
investigator in the HOPE-B study. "As a clinician, I look forward
to being able to provide a new treatment option that may help
patients treated with HEMGENIX become free from the regular
infusion schedule that many people living with hemophilia B rely on
to protect them from the debilitating effects of the
condition."
The multi-year clinical development program for HEMGENIX was led
by uniQure (Nasdaq: QURE), and sponsorship of the clinical trials
transitioned to CSL after it acquired global rights to
commercialize the treatment.
"Today's approval of the world's first gene therapy for
hemophilia B is an historic achievement based on more than a decade
of research and clinical development," said Matt Kapusta, Chief Executive Officer, uniQure.
"We have always believed that gene therapy had the potential to
provide transformative benefits to people living with hemophilia B
and are excited that the hemophilia community will have a new, safe
and effective treatment option available to them."
CSL Behring, a CSL business, will make HEMGENIX available for
eligible people with hemophilia B as soon as possible.
"CSL is proud to have been at the forefront of providing
life-changing medicines for rare diseases for over a century.
Today's historic approval builds on our promise to put patients
first in all that we do to discover, develop and deliver
biotherapeutics and vaccines that meet their needs," said
Bill Mezzanotte, Head of Research
& Development and Chief Medical Officer of CSL. "With HEMGENIX,
we now offer a comprehensive portfolio of innovative medicines for
hemophilia B, giving people living with the condition more choice
in treatments and better and more durable control over their
disease."
HEMGENIX is still currently under assessment by other regulatory
agencies.
About Hemophilia B
Hemophilia B is a life-threatening rare disease. People with the
condition are particularly vulnerable to bleeds in their joints,
muscles, and internal organs, leading to pain, swelling, and joint
damage. Current treatments for moderate to severe hemophilia B
include life-long prophylactic infusions of factor IX to
temporarily replace or supplement low levels of the blood-clotting
factor.
About HEMGENIX
HEMGENIX is a gene therapy that reduces the rate of abnormal
bleeding in eligible people with hemophilia B by enabling the body
to continuously produce factor IX, the deficient protein in
hemophilia B. It uses AAV5, a non-infectious viral vector, called
an adeno-associated virus (AAV). The AAV5 vector carries the Padua
gene variant of Factor IX (FIX-Padua) to the target cells in the
liver, generating factor IX proteins that are 5x-8x more active
than normal. These genetic instructions remain in the target cells,
but generally do not become a part of a person's own DNA. Once
delivered, the new genetic instructions allow the cellular
machinery to produce stable levels of factor IX.
About the Pivotal HOPE-B Trial
The pivotal Phase III
HOPE-B trial is an ongoing, multinational, open-label, single-arm
study to evaluate the safety and efficacy of HEMGENIX. Fifty-four
adult hemophilia B patients classified as having moderately severe
to severe hemophilia B and requiring prophylactic factor IX
replacement therapy were enrolled in a prospective, six-month or
longer observational period during which time they continued to use
their current standard of care therapy to establish a baseline
Annual Bleeding Rate (ABR). After the six-month lead-in period,
patients received a single intravenous administration of HEMGENIX
at the 2x10^13 gc/kg dose. Patients were not excluded from the
trial based on pre-existing neutralizing antibodies (NAbs) to
AAV5.
A total of 54 patients received a single dose of HEMGENIX in the
pivotal trial, with 53 patients completing at least 18 months of
follow-up. The primary endpoint in the pivotal HOPE-B study was ABR
52 weeks after achievement of stable factor IX expression (months 7
to 18) compared with the six-month lead-in period. For this
endpoint, ABR was measured from month seven to month 18 after
infusion, ensuring the observation period represented a
steady-state factor IX transgene expression. Secondary endpoints
included assessment of factor IX activity.
No serious adverse reactions were reported. One death resulting
from urosepsis and cardiogenic shock in a 77-year-old patient at 65
weeks following dosing was considered unrelated to treatment by
investigators and the company sponsor. A serious adverse event of
hepatocellular carcinoma was determined to be unrelated to
treatment with HEMGENIX by independent molecular tumor
characterization and vector integration analysis. No inhibitors to
factor IX were reported.
Important Safety Information (ISI)
What is HEMGENIX?
HEMGENIX®, etranacogene
dezaparvovec-drlb, is a one-time gene therapy for the treatment of
adults with hemophilia B who:
- Currently use Factor IX prophylaxis therapy, or
- Have current or historical life-threatening bleeding, or
- Have repeated, serious spontaneous bleeding episodes.
HEMGENIX is administered as a single intravenous infusion and
can be administered only once.
What medical testing can I expect to be given before and
after administration of HEMGENIX?
To determine your
eligibility to receive HEMGENIX, you will be tested for Factor IX
inhibitors. If this test result is positive, a retest will be
performed 2 weeks later. If both tests are positive for Factor IX
inhibitors, your doctor will not administer HEMGENIX to you. If,
after administration of HEMGENIX, increased Factor IX activity is
not achieved, or bleeding is not controlled, a post-dose test for
Factor IX inhibitors will be performed.
HEMGENIX may lead to elevations of liver enzymes in the blood;
therefore, ultrasound and other testing will be performed to check
on liver health before HEMGENIX can be administered. Following
administration of HEMGENIX, your doctor will monitor your liver
enzyme levels weekly for at least 3 months. If you have preexisting
risk factors for liver cancer, regular liver health testing will
continue for 5 years post-administration. Treatment for elevated
liver enzymes could include corticosteroids.
What were the most common side effects of HEMGENIX in
clinical trials?
In clinical trials for HEMGENIX, the most
common side effects reported in more than 5% of patients were liver
enzyme elevations, headache, elevated levels of a certain blood
enzyme, flu-like symptoms, infusion-related reactions, fatigue,
nausea, and feeling unwell. These are not the only side effects
possible. Tell your healthcare provider about any side effect you
may experience.
What should I watch for during infusion with
HEMGENIX?
Your doctor will monitor you for infusion-related
reactions during administration of HEMGENIX, as well as for at
least 3 hours after the infusion is complete. Symptoms may include
chest tightness, headaches, abdominal pain, lightheadedness,
flu-like symptoms, shivering, flushing, rash, and elevated blood
pressure. If an infusion-related reaction occurs, the doctor may
slow or stop the HEMGENIX infusion, resuming at a lower infusion
rate once symptoms resolve.
What should I avoid after receiving HEMGENIX?
Small
amounts of HEMGENIX may be present in your blood, semen, and other
excreted/secreted materials, and it is not known how long this
continues. You should not donate blood, organs, tissues, or cells
for transplantation after receiving HEMGENIX.
Please see full prescribing
information for HEMGENIX.
You are encouraged to report negative side effects of
prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call
1-800-FDA-1088.
You can also report side effects to CSL Behring's
Pharmacovigilance Department at 1-866-915-6958.
About CSL
CSL (ASX:CSL; USOTC:CSLLY) is a
leading global biotechnology company with a dynamic portfolio of
lifesaving medicines, including those that treat hemophilia and
immune deficiencies, vaccines to prevent influenza, and therapies
in iron deficiency, dialysis and nephrology. Since our start in
1916, we have been driven by our promise to save lives using the
latest technologies. Today, CSL – including our three businesses,
CSL Behring, CSL Seqirus and CSL Vifor – provides lifesaving
products to patients in more than 100 countries and employs 30,000
people. Our unique combination of commercial strength, R&D
focus and operational excellence enables us to identify, develop
and deliver innovations so our patients can live life to the
fullest. For inspiring stories about the promise of biotechnology,
visit CSLBehring.com/Vita and follow us on
Twitter.com/CSL.
For more information about CSL, visit CSL.com.
Media Contacts
Etanjalie Ayala
Commercial Operations Communications
Mobile: +1 610 297 1069
Email: etanjalie.ayala@cslbehring.com
Maria Tortoreto
R&D Communications
Mobile +1 201-248-5208
Email: maria.tortoreto@cslbehring.com
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