-
Navitoclax is being studied in myelofibrosis, a rare,
difficult-to-treat blood cancer
- Results
are from an exploratory analysis of 34 myelofibrosis patients who
received at least one dose of navitoclax in combination with
ruxolitinib after suboptimal response or disease progression with
ruxolitinib
monotherapy
-
Median overall survival was not reached for patients who had a ≥
1 grade improvement in bone marrow fibrosis or ≥ 20% variant allele
frequency reduction
- At the
time of analysis with > 2 year follow up the survival estimate
was 100% in patients who had improvements in bone marrow fibrosis
or variant allele frequency
- Results
were presented at the American Association for Cancer Research
annual meeting
NORTH
CHICAGO, Ill., April 12,
2022 /PRNewswire/ -- AbbVie (NYSE: ABBV) today
announced new data from a Phase 2 trial of navitoclax in
combination with ruxolitinib in patients with myelofibrosis. The
results were presented at the American Association for Cancer
Research annual meeting (AACR 2022, abstract #LB108). Navitoclax is
an investigational, first-in-class, oral BCL-XL/BCL-2
inhibitor that is designed to activate programmed cell death
(apoptosis) in cancer cells. Navitoclax and its safety and efficacy
are under evaluation as part of ongoing Phase 2 and registrational
Phase 3 studies.
"Myelofibrosis is a cancer that originates in the bone marrow,
leading to fibrosis. Currently, available therapies do not
address the underlying disease biology and have not shown a
consistent effect on both biomarkers of disease modification and
overall survival. Disease control with reversal of bone marrow
fibrosis is a key objective for improving patient outcomes," said
Mohamed Zaki, M.D., Ph.D., vice
president and global head of oncology clinical development at
AbbVie. "That's why we are especially pleased about these early
results of navitoclax in combination with ruxolitinib that indicate
its novel mechanism of action of inducing cell death may cause
reversal of bone marrow fibrosis and extend survival for patients
who respond to treatment."
Myelofibrosis is a rare, difficult-to-treat blood cancer that
results in excessive scar tissue formation (fibrosis) in the bone
marrow. Anti-fibrosis activity, measured by reversal of bone marrow
fibrosis (BMF) and reduction in driver gene variant allele
frequency (VAF) have been suggested as potential biomarkers to
measure disease modification in myelofibrosis, but their
association with a survival benefit have not been widely
described.1 These data build on AbbVie's history of
transforming standards of care in blood cancers with significant
unmet needs.
The results presented at AACR 2022 were from REFINE
(NCT03222609) – a Phase 2 trial evaluating navitoclax in
combination with ruxolitinib (a JAK1/2 inhibitor), which included
patients with myelofibrosis who had progressed on or had a
suboptimal response to at least 12 weeks of ruxolitinib
monotherapy. Median exposure to prior ruxolitinib was 91 weeks
(range: 19 weeks – 391 weeks) in the first 34 patients enrolled
earlier in the trial.
In the exploratory analysis of 32 patients who were evaluable
for improvements in BMF, 12 (38%) had a ≥1 grade improvement during
any time point in the study. For driver gene VAF reduction, 26
patients were evaluable and 6 (23%) achieved a ≥20% reduction at
week 24. Five patients achieved both BMF and VAF
responses.
Median overall survival (OS) for all patients was not reached as
presented previously by Harrison2 et al. For patients
who had a ≥1 grade improvement BMF median OS was not reached
compared with 28.5 months for patients who did not experience an
improvement. Similarly, median OS was also not reached for patients
who achieved a ≥20% driver gene VAF reduction versus 28.5 months
for patients who did not.
All 34 patients (100%) experienced at least one adverse event
(AE), and 15 (44%) experienced a serious adverse event
(SAE).2 The most common AEs of any grade were
thrombocytopenia (n= 30, 88%), diarrhea (n= 24, 71%), fatigue
(n= 21, 62%), and nausea (n= 13, 38%). The most common SAEs were
pneumonia (n= 4, 12%) and splenic infarction (n= 2,
6%).2 There were no SAEs of bleeding and
thrombocytopenia was manageable and reversible with dose
reduction/interruption of navitoclax and/or
ruxolitinib.2 REFINE was a dose-finding study and the
target dose of navitoclax was reduced subsequent to these
findings.
"Data obtained from this exploratory analysis holds promise for
potential future clinical research," said Jacqueline S. Garcia, M.D., Dana-Farber Cancer
Institute, assistant professor of medicine at Harvard Medical School. "What is most notable in
this analysis is the overall survival among patients who
demonstrate VAF and BMF responses and all patients were alive at
time of analysis. Patients in this Phase 2 trial had suboptimal
response to ruxolitinib at time of study entry and then had
navitoclax added to ruxolitinib on the trial. VAF and BMF responses
occurred despite the presence of high molecular risk mutations,
which suggests the potential efficacy of combination navitoclax and
ruxolitinib could be independent of underlying
risk factors."
About Navitoclax
Navitoclax is an investigational, oral BCL-XL/BCL-2
inhibitor. The BCL-2 family of proteins are known regulators of the
apoptosis pathway.3 Navitoclax is not approved by the
U.S. Food and Drug Administration (FDA). Its safety and efficacy
are under evaluation as part of ongoing Phase 2 and registrational
Phase 3 studies.
AbbVie is currently recruiting for two Phase 3 trials of
navitoclax (TRANSFORM-1 and TRANSFORM-2) in combination with
ruxolitinib for the treatment of myelofibrosis that will enroll
more than 500 patients. The company anticipates pivotal trial
readouts and regulatory submission for navitoclax in 2023.
About the REFINE Study
REFINE is a Phase 2, open-label, multicenter study evaluating
the tolerability and efficacy of navitoclax alone or when added to
ruxolitinib in patients with myelofibrosis.1 The primary
outcome measure is the percentage of patients who achieve Spleen
Volume Reduction of greater than or equal to 35% (SVR35) from
baseline to Week 24. Secondary outcomes measures include percentage
of participants achieving 50% reduction in Total Symptom Score from
baseline to Week 24 and change in grade of bone marrow fibrosis
assessed according to the European Consensus Grading System. More
information can be found on
www.clinicaltrials.gov (NCT03222609).
About Myelofibrosis
Myelofibrosis is a rare, difficult-to-treat blood cancer that
results in excessive scar tissue formation (fibrosis) in the bone
marrow. Patients living with myelofibrosis experience symptoms such
as an enlarged spleen, fatigue, weakness, and severe anemia, that
are often debilitating and greatly impact quality of life.
Myelofibrosis also carries a risk of transformation to more
aggressive disease such as acute myeloid leukemia.3
About AbbVie
AbbVie's mission is to discover and deliver innovative medicines
that solve serious health issues today and address the medical
challenges of tomorrow. We strive to have a remarkable impact on
people's lives across several key therapeutic areas: immunology,
oncology, neuroscience, eye care, virology, women's health and
gastroenterology, in addition to products and services across its
Allergan Aesthetics portfolio. For more information about AbbVie,
please visit us at www.abbvie.com. Follow @abbvie on
Twitter, Facebook, Instagram, YouTube and LinkedIn.
Forward-Looking
Statements
Some statements in this news release are, or may be
considered, forward-looking statements for purposes of the Private
Securities Litigation Reform Act of 1995. The words "believe,"
"expect," "anticipate," "project" and similar expressions, among
others, generally identify forward-looking statements. AbbVie
cautions that these forward-looking statements are subject to risks
and uncertainties that may cause actual results to differ
materially from those indicated in the forward-looking statements.
Such risks and uncertainties include, but are not limited to,
failure to realize the expected benefits from AbbVie's acquisition
of Allergan plc ("Allergan"), failure to promptly and effectively
integrate Allergan's businesses, competition from other products,
challenges to intellectual property, difficulties inherent in the
research and development process, adverse litigation or government
action, changes to laws and regulations applicable to our industry
and the impact of public health outbreaks, epidemics or pandemics,
such as COVID-19. Additional information about the economic,
competitive, governmental, technological and other factors that may
affect AbbVie's operations is set forth in Item 1A, "Risk Factors,"
of AbbVie's 2021 Annual Report on Form 10-K, which has been filed
with the Securities and Exchange Commission, as updated by its
subsequent Quarterly Reports on Form 10-Q. AbbVie undertakes no
obligation to release publicly any revisions to forward-looking
statements as a result of subsequent events or developments, except
as required by law.
References:
- Mascarenhas J, Komrokji RS, Palandri F, et al. Randomized,
single-blind, multicenter Phase II study of two doses imetelstat in
relapsed or refractor myelofibrosis. J Clin Oncol.
2021;10;39(26):2881-2892.
- Harrison C, Garcia J, Somervaille T, et al. Addition of
Navitoclax to Ongoing Ruxolitinib Therapy for Patients With
Myelofibrosis With Progression or Suboptimal Response: Phase II
Safety and Efficacy. J Clin Oncol. 2022; JCO2102188.
- Tsujimoto Y. (1998). Role of Bcl-2 family proteins in
apoptosis: apoptosomes or mitochondria?. Genes to cells: devoted to
molecular & cellular mechanisms, 3(11), 697–707.
https://doi.org/10.1046/j.1365-2443.1998.00223.x
View original
content:https://www.prnewswire.com/news-releases/abbvie-presents-positive-investigational-navitoclax-combination-data-in-phase-2-refine-study-suggesting-anti-fibrosis-activity-for-patients-with-myelofibrosis-301523415.html
SOURCE AbbVie