- Exploratory analysis from Cohort 3 of the Phase 2
REFINE study presented in an oral session at ASH
NORTH
CHICAGO, Ill., Dec. 10,
2022 /PRNewswire/ -- AbbVie (NYSE:
ABBV) today announced new data from Cohort 3 of its Phase 2 REFINE
study of investigational navitoclax in combination with ruxolitinib
in JAK inhibitor-naïve patients with myelofibrosis (MF). The
exploratory analysis suggests the combination of navitoclax and
ruxolitinib led to reductions in bone marrow fibrosis (BMF) and
variant allele frequency (VAF) for common genetic mutations found
in individuals with myelofibrosis that may indicate potential
disease modification.1 The findings were shared in an
oral presentation (abstract #237) at the 64th American
Society of Hematology Annual Meeting & Exposition
(ASH).
"While the current standard of care for patients with
myelofibrosis can improve disease symptoms, impact on underlying
disease biology is limited. It is our hope that patients have an
option that goes beyond symptom control," said
Mohamed Zaki, M.D., Ph.D., vice
president and global head of oncology clinical development, AbbVie.
"Consistent with previous evidence, these results suggest
navitoclax combination may have disease modifying potential, both
as an anti-fibrosis agent and by reducing variant allele frequency
of driver mutations."
REFINE (NCT03222609) is a Phase
2 non-randomized open-label multi-cohort study evaluating the
safety and efficacy of navitoclax alone or in combination with
ruxolitinib in MF.2
These data build on AbbVie's history of transforming
standards of care in blood cancers, including recent presentations
of investigational navitoclax data from the REFINE study earlier
this year at the American Association for Cancer
Research (AACR) Annual Meeting and the
European Hematology Association (EHA) Annual
Congress.
The findings presented at ASH were based on an exploratory
analysis of 32 JAK inhibitor-naïve patients with MF
from Cohort 3 of the Phase 2 REFINE study. The primary endpoint was
spleen volume reduction of ≥35 percent (SVR35) from baseline at
week 24.1 Key secondary and exploratory endpoints
evaluated in this analysis were a reduction in BMF and a reduction
in VAF for the driver gene mutations (JAK2V617,
CALR, MPL or Triple-negative),
respectively.1
In this exploratory analysis, SVR35 at week 24 was
observed in higher-risk groups, improving over time. The four poor
prognosis subgroups were: Type (primary or secondary)
of MF (primary MF, 59 percent [n = 10/17]; age (≥75 years, 50
percent [n = 4/8]); prognostic risk score, as measured by Dynamic
International Prognostic Scoring System or DIPSS (intermediate-2,
63 percent [n = 12/19]; high, 33 percent [n = 1/3]); and presence
of high molecular risk (HMR) mutations (47 percent [n =
9/19].1
In Cohort 3, BMF grade improvement was evaluable in 81
percent (26/32) of patients.1 Of these study
participants, 35 percent (9/26) achieved ≥ 1 grade
improvement at any time during treatment with a median
time-to-improvement of 12.3 weeks.1 Complete resolution
of BMF was observed in 22 percent (2/9) of
patients.1
Reduction in driver gene mutation VAF > 20% from
baseline at week 12 or 24 was observed in 50 percent (14/28) of
patients, while 18 percent (5/28) of patients achieved > 50% VAF
reduction from baseline. There were no differences in > 20% VAF
reductions from baseline to week 12 or 24 between those with or
without HMR mutations (47 percent [7/15] versus 54 percent [7/13],
respectively).
Preliminary safety analysis identified no new safety
signals. Twenty-five (78 percent) patients reported one or more
adverse events (AE). The most common grade ≥3 AEs were
thrombocytopenia (47 percent), anemia (34 percent), and neutropenia
(25 percent). 9.4 percent of patients discontinued therapy due
to an AE.3
"These results are promising for patients who need a
treatment option that goes beyond just symptom control," said
Francesco Passamonti, full professor of hematology, University
of Insubria and chief, hematology, Varese Hospital, Italy. "The suggestion of disease modification
in this analysis from combination therapy with navitoclax is
encouraging, particularly when combined with clinical efficacy in
terms of SVR35 rates in the higher risk groups that improved over
time."
About Navitoclax
Navitoclax is an
investigational, oral BCL-XL/BCL-2 inhibitor. Navitoclax is not
approved by any health authority worldwide at this time. Its safety
and efficacy are under evaluation as part of ongoing Phase 2 and
registrational Phase 3 studies.
AbbVie has an extensive late-stage clinical trial program
for investigational navitoclax that is currently enrolling. Please
visit us here for more information about
enrolling in a clinical trial.
About the REFINE Study
REFINE is a
multi-cohort, Phase 2, randomized, open-label, multicenter study
evaluating the tolerability and efficacy of navitoclax alone or
when added to ruxolitinib in patients with myelofibrosis
(MF).2 The primary outcome measure is the percentage of
patients who achieve spleen volume reduction of greater than or
equal to 35 percent (SVR35) from baseline to week 24.2
Secondary outcomes measures include percentage of participants
achieving 50 percent reduction in total symptom score from baseline
to week 24; anemia response every 12 weeks up to approximately 96
weeks, measured according to current International Working
Group-Myeloproliferative Neoplasms Research and European
LeukemiaNet (IWG-MRT/ELN) criteria; and change in grade of bone
marrow fibrosis assessed according to the European Consensus
Grading System.2
Data presented at ASH 2022 include safety and efficacy
results from Cohort 3 of REFINE (n=32). Patients in Cohort 3 had
primary or secondary MF with splenomegaly (DIPSS ≥ intermediate-1)
and had not received JAK-2 therapy or bromodomain and extra
terminal motif (BET) inhibitors prior to enrollment. The primary
endpoint of SVR35 was assessed by MRI conducted by central review.
Key secondary and exploratory endpoints evaluated in this analysis
were a reduction in BMF obtained from BM biopsies by local
evaluation and a reduction in VAF for the driver gene mutations
(JAK2V617, CALR, or MPL), respectively. Studied HMR mutations
included ASXL1, EZH2, SRSF2, IDH1/2, and U2AF1 p.Q157. Driver gene
VAF and HMR mutations were determined in whole blood with a 50-gene
focus myeloid next-generation sequencing panel. The findings
presented at ASH 2022 are representative of data from Cohort 3 of
the REFINE study as of February 7,
2022.
More information about the REFINE study can be found
at https://www.clinicaltrials.gov/
(NCT03222609).
About Myelofibrosis
Myelofibrosis
(MF) is a rare, difficult-to-treat blood cancer that results in
excessive scar tissue formation (fibrosis) in the bone marrow.
Patients living with MF experience symptoms such as an enlarged
spleen, fatigue, weakness, and severe anemia which are often
debilitating and greatly impact quality of life. MF also carries a
risk of transformation to more aggressive disease such as acute
myeloid leukemia.4
About AbbVie in Oncology
At AbbVie,
we are committed to transforming standards of care for multiple
blood cancers while advancing a dynamic pipeline of investigational
therapies across a range of cancer types. Our dedicated and
experienced team joins forces with innovative partners to
accelerate the delivery of potentially breakthrough medicines. We
are evaluating more than 20 investigational medicines in over 300
clinical trials across some of the world's most widespread and
debilitating cancers. As we work to have a remarkable impact on
people's lives, we are committed to exploring solutions to help
patients obtain access to our cancer medicines. For more
information, please visit
https://www.abbvie.com/oncology and our
Blood Cancer Press Kit page.
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 our 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:
- Passamonti F, Foran J, Tandra A, et al. The
Combination of Navitoclax and Ruxolitinib in JAK Inhibitor-Naïve
Patients With Myelofibrosis Mediates Responses Suggestive of
Disease Modification. [Oral Presentation #237]. Presented at 2022
American Society of Hematology (ASH) Annual Meeting and Exhibition,
December 10-13, 2022.
- ClinicalTrials.gov. A Study Evaluating Tolerability and
Efficacy of Navitoclax Alone or in Combination With Ruxolitinib in
Participants With Myelofibrosis (REFINE). NCT03222609. Available at
https://www.clinicaltrials.gov/ct2/show/NCT03222609.
Last accessed October
2022.
- Navitoclax plus ruxolitinib in JAK inhibitor-naïve
patients with myelofibrosis: Preliminary safety and efficacy in a
multicenter, open-label Phase 2 study. [Oral Presentation S197].
Presented at European Hematology Association 2022 Congress (EHA
2022), June 9-12, 2022.
- 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
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