- Data is supportive of early intervention in myelofibrosis to
achieve improved clinical outcomes in spleen volume reduction
(SVR), symptom score, bone marrow fibrosis (BMF), and
anemia
- Results are from an exploratory analysis of navitoclax plus
ruxolitinib from Cohort 3 of the Phase 2 REFINE study in JAK
inhibitor naïve myelofibrosis patients
NORTH
CHICAGO, Ill., June 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), a rare and
difficult to treat blood cancer. These preliminary findings show
spleen volume and symptomatic improvement in this cohort. These
data are consistent with previously observed data from
relapsed/refractory patients in Cohort 1a1 and will be
shared in an oral presentation at the 2022 European Hematology
Association (EHA) Annual Congress (Abstract #S197).2
REFINE 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.
"Current treatment options for myelofibrosis are limited and
targeted toward controlling disease symptoms," said Mohamed Zaki, M.D., Ph.D., vice president and
global head of oncology clinical development, AbbVie. "Together
with pre-clinical findings, early results of this study
demonstrating anti-fibrosis activity of navitoclax in combination
with ruxolitinib are promising. Specifically, the data findings
regarding reduction in spleen volume, symptoms and bone marrow
fibrosis help support the further exploration of disease
modification in myelofibrosis."
The results presented at EHA 2022 were from a preliminary
analysis of 32 JAK inhibitor naïve MF patients from Cohort 3 of the
Phase 2 REFINE trial (NCT03222609).2 The primary
endpoint was spleen volume reduction of ≥35 percent (SVR35) from
baseline at week 24.2 Key secondary endpoints
include ≥50 percent reduction in total symptom score (TSS50) at
week 24, anemia response and BMF reduction.2
In the results, SVR35 was achieved by 63 percent of evaluable
patients at week 24 (20/32) and by 78 percent at any time on
treatment (25/32).2 At week 24, 41 percent (11/27)
of evaluable patients with measurable baseline symptoms reached
TSS50; notably, 67 percent of patients (18/27) met this endpoint at
any time during the study.2 In this cohort, 35
percent of evaluable patients, with available fibrosis grade at
baseline and during the study, (9/26) achieved reduction in BMF by
≥1 grade at any time during the study with three patients
experiencing ≥2 grade reductions in
BMF.2 Additionally, 40 percent of patients
evaluable for anemia response (6/15) experienced improvement in
anemia, a common clinical feature of MF.2
Preliminary safety analysis identified no new safety signals.
Thirty-one (97 percent) patients reported one or more adverse event
(AE).1 The most common Grade ≥3 AEs were
thrombocytopenia (47 percent), anemia (34 percent), and neutropenia
(25 percent).1 Seven patients (22 percent) reported
experiencing serious AEs.1 Three patients (9
percent) experienced an AE leading to navitoclax discontinuation
and three patients (9 percent) reported an AE leading to
ruxolitinib discontinuation.2
"These data reinforce the importance of early intervention in
myelofibrosis and the potential to achieve improved clinical
outcomes," said Francesco Passamonti, Full Professor of
Hematology, University of Insubria and Chief, Hematology, Varee
Hospital. "These preliminary results show good responses to
combination therapy with navitoclax that may continue to improve
over time."
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) or 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. For more
information about enrolling in a clinical trial, please visit us
here.
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).4 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. Secondary outcomes measures
include percentage of participants achieving 50 percent 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.
Data presented at EHA 2022 include preliminary safety and
efficacy results from Cohort 3 of REFINE (n=32). Patients in Cohort
3 had primary or secondary MF with splenomegaly and had not
received JAK-2 therapy or BET inhibitors prior to enrollment. Data
presented at EHA 2022 are representative of data from Cohort 3 of
the REFINE study as of February 7,
2022.
Data included in the official EHA 2022 Abstract Book are
representative of data from Cohort 3 of the REFINE study as of
October 4, 2021.
More information can be found on 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, that 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 http://www.abbvie.com/oncology.
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:
- Ruxolitinib with Navitoclax Is Efficacious and Safe in
Myelofibrosis. Cancer Discovery 1 May
2022; 12 (5): OF4.
https://doi.org/10.1158/2159-8290.CD-RW2022-037.
- 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.
- 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
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