- Data follow the historic approval of the first gene therapy for
hemophilia B, which 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
- 18-month data support the efficacy and safety of
HEMGENIX® and the ongoing benefit of this treatment
- HEMGENIX® is approved for adults with hemophilia B
in the United States, European
Union and European Economic Area
KING OF
PRUSSIA, Penn., Feb. 23,
2023 /PRNewswire/ -- Global biotechnology leader CSL
(ASX: CSL) today announced the publication in the New England
Journal of Medicine (NEJM) (Vol. 388 No. 8) results from the
pivotal HOPE-B clinical study evaluating the efficacy, durability
and safety of HEMGENIX® (etranacogene
dezaparvovec-drlb). HEMGENIX® is the first and only
gene therapy approved 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.
Results from the HOPE-B trial, the largest gene therapy study in
hemophilia B to date, were considered by the authors to demonstrate
that HEMGENIX® is superior to routine factor IX
prophylaxis in Annualized Bleeding Rate (ABR), and demonstrated
significant improvements in factor IX activity, factor IX therapy
consumption, factor IX infusion rate, and spontaneous and joint
bleeding ABR. Increased factor IX activity was also apparent from
week 3 and maintained over 18 months. There were no serious
treatment-related adverse events.
Notably, the results published in NEJM show the ABR of
spontaneous bleeding episodes and all joint bleeding episodes
decreased by 71% (95% CI: 0.12, 0.71) and 78% (95% CI: 0.10, 0.46),
respectively, from lead-in period to post-treatment. Further, the
authors found 96.3% of patients discontinued factor IX prophylaxis
from day 21 through month 18 post-treatment (the discontinuation
rate in the approved U.S. HEMGENIX® product label is
94%). Annualized factor IX infusions also significantly decreased
from 72.5 infusions per participant during lead-in period
(95% CI: 63.6, 82.7) to 2.5 infusions
(95% CI: 0.92, 6.96) post-treatment.
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.
"The results published in NEJM add to the established body of
evidence demonstrating the long-term efficacy and safety of
HEMGENIX® and confirm that this innovative new
medicine not only restores blood clotting factor to near normal
levels and significantly reduces factor use, but also that gene
therapy may reduce the burden of care and improve quality of
life for people living with 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 lead investigator of the HOPE-B study. "HOPE-B was also the
first and only phase 3 study to demonstrate efficacy of a gene
therapy for hemophilia B in individuals with circulating
neutralizing antibodies that have the potential to interfere with
the effects of treatment. Results from HOPE-B suggest that
HEMGENIX® may be effective in a broad range of
hemophilia B patients, regardless of prior exposure to common
adeno-associated viruses."
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. HEMGENIX® was approved
in November 2022 by the U.S. Food and
Drug Administration (FDA), and in February
2023 by the European Commission (EC) for the European Union
and European Economic Area.
"We are proud to showcase the HOPE-B trial data in such a
prestigious publication," said Brahm
Goldstein, MD, Vice President, Research and Development,
Hematology at CSL. "These results underscore the benefits of
this novel approach and reinforce that those treated with
HEMGENIX® will likely achieve durable factor IX activity
levels and remain free of prophylactic factor IX replacement for
years following a single administration. CSL remains steadfast in
our commitment to deliver on our promise of innovation for people
living with rare bleeding disorders."
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 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 24-month data presented at the 54th
American Society of Hematology (ASH) 2022 Annual Meeting and
Exposition and at The European Association for Haemophilia and
Allied Disorders (EAHAD) 2023 Annual Meeting 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.
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
Greg Healy
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Email: greg.healy@cslbehring.com
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In Australia
Kim O'Donohue
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Email: kim.odonohue@csl.com.au
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Email: Jimmy.Baker@csl.com.au
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