- HEMGENIX® is the first and only gene therapy
approved by the U.S. Food and Drug Administration (FDA) for the
treatment of hemophilia B and to show sustained efficacy and safety
at three years post-treatment
- Long-term data continues to show a one-time infusion of
HEMGENIX offers elevated and sustained factor IX activity levels
for years and significantly reduces the rate of annual bleeds
versus factor IX prophylaxis with a favorable safety profile
- At three years post-treatment with HEMGENIX, 94% of patients
remained free of continuous prophylactic treatment
KING OF
PRUSSIA, Pa., Dec. 11,
2023 /PRNewswire/ -- Global biotechnology leader CSL
(ASX: CSL; USOTC: CSLLY) today announced the three-year results
from the pivotal HOPE-B study confirming continued long-term
durability and safety of HEMGENIX® (etranacogene
dezaparvovec-drlb) following a one-time infusion in people living
with hemophilia B. The data showing that a one-time infusion of
HEMGENIX offers elevated and sustained factor IX activity
levels for years were presented in an oral presentation at the 65th
American Society of Hematology (ASH) Annual Meeting and Exposition.
HEMGENIX is the first and only 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.
"The long-term follow-up data from the HOPE-B study reinforces
that a one-time treatment with HEMGENIX can produce elevated and
sustained factor IX levels and reduce the rate of annual bleeds for
years in people living with hemophilia B," said Dr. Steven Pipe, Professor of Pediatrics and
Pathology at the University of Michigan
and principal investigator of the HOPE-B pivotal trial. "Most
importantly, the data show that nearly all the Phase III trial
participants three years post-treatment with HEMGENIX have remained
free from the need for regular prophylactic infusions, which is
groundbreaking for the hemophilia B community."
The Phase III, open label, single-dose, single arm HOPE-B trial
included 54 male participants with severe or moderately severe
hemophilia B with or without pre-existing AAV5 neutralizing
antibodies. Of the 54 participants who received HEMGENIX, 52
completed three years of follow-up. HEMGENIX produced mean factor
IX levels of 41.5 IU/dL at year one, 36.7 IU/dL at year two and
38.6 IU/dL at year three post-treatment. In addition, 94% (51 out
of 54) of patients remained free of continuous prophylactic
therapy.
The three-year data also demonstrated that the mean annualized
bleeding rate (ABR) for all bleeds was reduced by 64% during months
7-36 of the study (mean ABR 1.52 vs. 4.17 during the lead-in
period; p=0.0004), sustaining the same bleed reduction that
satisfied the study's primary endpoint. The FDA-approved
prescribing information for HEMGENIX shows that ABR for all bleeds
was reduced by 54% during months 7-18 of the study. Median bleeds
per participant decreased from 2.0 during the lead-in period and
remained stable at 0.0 during years one to three.
There were no serious adverse events related to treatment with
HEMGENIX. HEMGENIX was generally well-tolerated, with most
treatment-emergent adverse events (76%) considered mild; 95% of
adverse events occurred before six months post-treatment. The most
common adverse events were an increase in alanine transaminase
(ALT), for which nine (16.7%) participants received supportive care
with reactive corticosteroids for a mean duration of 81.4 days
(standard deviation: 28.6; range: 51-130 days).
"Gene therapy is a novel treatment that addresses unmet needs in
the hemophilia B community and the data presented at ASH continues
to provide confidence in the clinical benefits of HEMGENIX," said
Steven Pascoe, M.D., Chief Medical
Officer, CSL. "As part of our commitment to the hemophilia B
community, we will continue to follow the participants from the
HOPE-B study as well as those who have been treated with HEMGENIX
post FDA approval to generate additional evidence supporting the
long-term safety, efficacy and durability of this one-time
treatment. We encourage healthcare professionals to continue to
have open conversations with their patients about individual
treatment goals and whether HEMGENIX may be an appropriate
treatment option."
In addition to the presentation of the three-year results of the
HOPE-B trial, two posters on HEMGENIX were presented evaluating
HEMGENIX in patients with comorbidities. The first (Abstract #2258)
assessed HEMGENIX in hemophilia B patients with a history of
chronic hepatitis C and hepatitis B infections and the second
(Abstract #2256) investigated those with human immunodeficiency
virus (HIV). Additionally, an analysis on the indirect
treatment comparison of HEMGENIX and factor IX prophylaxis was
recently published in Haemophilia.
HEMGENIX also has been granted conditional marketing
authorization by the European Commission (EC) for the European
Union and European Economic Area, and the United Kingdom's Medicines and Healthcare
products Regulatory Agency (MHRA), as well as authorization by
Health Canada. The multi-year clinical development of HEMGENIX was
led by uniQure (Nasdaq: QURE) and sponsorship of the clinical
trials transitioned to CSL after it licensed global rights to
commercialize the treatment. Earlier this year, CSL announced the
first person living with hemophilia B had received HEMGENIX.
For more information on HEMGENIX, please visit
www.Hemgenix.com.
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 at least 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 52 patients completing at least three years 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 treatment-related 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.
Long-term three-year data presented at the 65th American Society
of Hematology (ASH) 2023 Annual Meeting and Exposition continue to
reinforce the potential long-lasting efficacy and safety of
HEMGENIX and the ongoing benefit of this treatment for people
living with hemophilia B.
About Hemophilia B
Hemophilia B is a life-threatening rare disease caused by a
mutation on the F9 gene, resulting in low levels of functional
clotting factor IX. 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.
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 global
biotechnology company with a dynamic portfolio of lifesaving
medicines, including those that treat haemophilia and immune
deficiencies, vaccines to prevent influenza, and therapies in iron
deficiency 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 32,000 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 CSL.com/Vita and follow us
on Twitter.com/CSL.
For more information about CSL, visit CSL.com.
Media Contacts
Etanjalie Ayala
Mobile: +1 610 297 1069
Email: etanjalie.ayala@cslbehring.com
Maria Tortoreto
Mobile: +1 201 248 5208
Email: maria.tortoreto@cslbehring.com
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