- Long-term data from the pivotal HOPE-B study show a one-time
infusion of HEMGENIX generated elevated and sustained mean factor
IX levels and reduced the rate of annual bleeding
- 24-month results reinforced safety of treatment, with no
serious treatment-related adverse effects related to HEMGENIX
infusion
- HEMGENIX, recently approved by the U.S. Food and Drug
Administration, is the first and only gene therapy for the
treatment of certain adults living with hemophilia B
KING OF
PRUSSIA, Pa., Dec. 10,
2022 /PRNewswire/ -- Global biotechnology leader
CSL (ASX: CSL) today announced the presentation of data
affirming the long-term durability and safety of single-infusion
HEMGENIX® (etranacogene dezaparvovec-drlb) in the treatment of
certain adults living with hemophilia B at the 64th
American Society of Hematology (ASH) Annual Meeting. Results from
the pivotal HOPE-B study, the largest gene therapy study in
hemophilia B to date, demonstrated that after two years of
follow-up, adults with severe or moderately severe hemophilia B
treated with a one-time infusion of HEMGENIX generated elevated and
sustained mean factor IX activity levels and durable hemostatic
protection.
"Gene therapy has great potential for rare bleeding disorders,
and these results demonstrate long-lasting increases in factor IX
activity levels, reaching levels near the normal range seen in
people without hemophilia B," said Steven
Pipe, M.D., professor of pediatrics and pathology and
pediatric medical director of the hemophilia and coagulation
disorders program at the University of
Michigan, and principal investigator of the HOPE-B pivotal
trial. "These data reinforce that people with hemophilia B who have
received HEMGENIX would likely achieve durable factor IX activity
levels for years following a one-time infusion."
Key Data from the HOPE-B 24-Month Extension
In
the open-label, single-arm HOPE-B study, 54 adult male participants
with severe or moderately severe hemophilia B, with or without
pre-existing AAV5 neutralizing antibodies were infused with a
single dose of HEMGENIX. HEMGENIX produced mean factor IX activity
of 39.0 IU/dL at six months and 36.9 IU/dL at 18 months post
infusion, which was sustained at 36.7 IU/dL in the long-term
follow-up data at two years. 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.
In an abstract that CSL Behring will present, the data
demonstrate the ABR for all bleeds was reduced by 64% during months
7-24 of the study (mean ABR 1.51 vs. 4.18 during the lead-in
period; p=0.0002), 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. Treatment with
HEMGENIX also reduced mean unadjusted annualized factor IX
consumption by 96% from the lead-in period (257,339
IU/year/participant) to months 19–24 (9751 IU/year/participant;
p<0.0001).
Of the 557 treatment-emergent adverse events reported 24-months
post-infusion, 424 (76%) were mild, 115 (21%) were moderate and 18
(3%) were severe. A total of 38 participants (70.4%) experienced 93
treatment-related adverse events, with only one occurring during
months 18-24. There were no serious adverse effects related to
treatment; a serious AE of hepatocellular carcinoma was determined
by independent molecular genomic and integration analysis to be
unrelated to treatment.
"The results presented at ASH continue to support the potential
long-lasting efficacy and safety of HEMGENIX and the ongoing
benefit of this treatment for people living with hemophilia B,"
said Brahm Goldstein, M.D., Vice
President, Research and Development, Hematology at CSL. "HEMGENIX
offers eligible people living with hemophilia B more choice in
treatments and underscores CSL's promise to deliver disruptive
innovations, like gene therapy, that have the potential to improve
the lives of people living with rare and serious diseases in our
therapeutic areas of focus, like hematology."
CSL presented two additional abstracts at the ASH Annual
Meeting:
- Durability of Bleeding Protection and Factor IX Activity Levels
Are Demonstrated in Individuals with and without Adeno-Associated
Virus Serotype 5 Neutralizing Antibodies (Titers <1:700) with
Comparable Safety in the Phase 3 HOPE-B Clinical Trial of
Etranacogene Dezaparvovec Gene Therapy for Hemophilia B
- Durability of Factor IX Activity and Bleeding Rate in People
with Severe or Moderately Severe Hemophilia B after 5 Years of
Follow-up in the Phase 1/2 Study of AMT-060, and after 3 Years of
Follow-up in the Phase 2b and 2 Years
of Follow-up in the Phase 3 Studies of Etranacogene Dezaparvovec
(AMT-061)
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. HEMGENIX is still currently under
assessment by other regulatory agencies.
CSL medical representatives will be available at booth number
228 throughout the ASH Annual Meeting.
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 the first and only one-time gene therapy approved for
the treatment of adults living 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.
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 elevated 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
Maria Tortoreto
R&D Communications
Mobile: +1 201 248 5208
Email: maria.tortoreto@cslbehring.com
Etanjalie Ayala
Commercial Operations Communications
Mobile: +1 610 297 1069
Email: etanjalie.ayala@cslbehring.com
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