– Treatment with axatilimab resulted in an
overall response rate (ORR) of 67% across all patients; and an ORR
of 82% in patients dosed at 1 mg/kg every 2 weeks in the Phase 2
portion of the trial –
– Broad multi-organ clinical benefit including
in lung, skin, and joints and fascia observed in heavily pretreated
patient population –
WALTHAM,
Mass. and WILMINGTON,
Del., Dec. 5, 2022 /PRNewswire/ -- Syndax
Pharmaceuticals, Inc. (Nasdaq: SNDX) and Incyte (Nasdaq: INCY)
today announced that results from the Phase 1/2 trial of
axatilimab, Syndax's anti-CSF-1R antibody, in patients with
recurrent or refractory chronic graft-versus-host disease (cGVHD)
following two or more prior lines of therapy, were published in the
Journal of Clinical Oncology.
A total of 40 patients with refractory disease who received a
median of four prior systemic therapies, some of which included
ibrutinib, ruxolitinib and belumosudil, were treated in the Phase
1/2 dose escalation trial. Thirty-nine patients were evaluable for
response as of the data cutoff. All study participants were treated
for a median duration of 29 weeks, with all responding patients
treated for a median duration of 38 weeks at the time of data
cut-off. Results showed:
- Overall response rate by cycle 7 day 1 was 82% (18/22) in the
Phase 2 cohort (1mg/kg every two weeks) and 67% (26/39) among all
evaluable patients treated in the dose escalation study. Best ORR
(complete response + partial response) observed at any point during
the study in all patients treated was 69% (27/39).
- Median duration of response for Phase 2 responding patients was
not reached; 33% of patients experiencing sustained response
lasting 20 weeks or longer.
- A decrease in glucocorticoids doses was observed in 52% of
responding patients.
- Responses were observed across a range of organ systems with
difficult to treat manifestations such as lung (5/16), skin (5/35),
and joints and fascia (19/31).
- A clinically meaningful disease improvement using the Lee
Symptom Score of at least 7 points was seen in 58% (21/36) of all
evaluable patients.
Axatilimab was well tolerated with a favorable safety profile in
this refractory population. The most common adverse events were
consistent with on-target effects of CSF-1R inhibition. In the
Phase 1 cohort, two dose limiting toxicities were reported, both at
the 3 mg/kg every two weeks dose. There were no ≥Grade 3
on-target toxicities of CSF-1R blockade seen in the Phase 2 cohort.
There was no incidence of cytomegalovirus or other viral
reactivation, and no apparent increases in risk for
infection. Serious adverse events occurred in 40% (16/40) of
patients, with seven (18%) patients discontinuing the study
intervention due to adverse events, four (10%) of which were deemed
treatment-related.
"We believe axatilimab is well positioned to potentially be a
first- and best-in-class anti-CSF-1R antibody for cGVHD," said
Kate Madigan, M.D., Chief Medical
Officer of Syndax. "The robust, durable responses and
multi-organ clinical benefit observed in this Phase 1/2 trial in
refractory patients support the potential for axatilimab to serve
as an effective intervention in this underserved
population."
"The results of this Phase 1/2 dose finding study are very
encouraging regarding the ability of axatilimab to provide
meaningful clinical responses in chronic GVHD patients that have
been refractory to multiple prior therapies" said Carrie Kitko, M.D., Medical Director of the
Pediatric Stem Cell Transplant Program at the Vanderbilt-Ingram
Cancer Center, and the corresponding author of the Phase 1/2
publication. "Combining both anti-inflammatory and anti-fibrotic
effects through the targeting of disease associated macrophages
would be particularly exciting for this patient population that
would benefit from a reduction in sclerotic and fibrotic
manifestations of chronic GVHD. In the past simply stopping further
progression of those manifestations was considered a "win", but
some of these patients are actually having improvements in joint
range of motion and skin tightening."
The article, titled "Axatilimab for chronic graft-versus-host
disease after failure of at least two prior systemic therapies:
results of a Phase 1/2 study," is available online.
About Chronic
Graft-Versus-Host Disease
Chronic graft-versus-host disease, an immune response of the
donor-derived hematopoietic cells against recipient tissues, is a
serious, potentially life-threatening complication of allogeneic
hematopoietic stem cell transplantation which can last for years.
Chronic GVHD is estimated to develop in approximately 40% of
transplant recipients, and affects approximately 14,000 patients in
the U.S.1,2 Chronic GVHD typically manifests
across multiple organ systems, with skin and mucosa being commonly
involved, and is characterized by the development of fibrotic
tissue.3
About Axatilimab
Axatilimab is an investigational monoclonal antibody that
targets colony stimulating factor-1 receptor, or CSF-1R, a cell
surface protein thought to control the survival and function of
monocytes and macrophages. In pre-clinical models, inhibition of
signaling through the CSF-1 receptor has been shown to reduce the
number of disease-mediating macrophages along with their monocyte
precursors, which has been shown to play a key role in the fibrotic
disease process underlying diseases such as cGVHD and IPF. Phase
1/2 data of Axatilimab in cGVHD demonstrating its broad activity
and tolerability was last presented at the 63rd American Society of
Hematology Annual Meeting. Axatilimab was granted Orphan Drug
Designation by the U.S. Food and Drug Administration for
the treatment of patients with cGVHD and IPF. In September
2021, Syndax and Incyte entered into an exclusive worldwide
co-development and co-commercialization license agreement for
axatilimab. Axatilimab is being developed under an exclusive
worldwide license from UCB entered into between Syndax and UCB in
2016.
Enrollment in the Company's global pivotal Phase 2 AGAVE-201
Phase 2 study evaluating the efficacy, safety, and tolerability of
axatilimab in patients with recurrent or refractory active cGVHD
who have received at least two prior lines of systemic therapy is
complete, and topline data is expected mid-2023. Additionally, a
Phase 1 combination trial of ruxolitinib and axatilimab, led by
Incyte, is in preparation and expected to initiate by end of the
first quarter of 2023, and a Phase 2b
trial of axatilimab in patients with idiopathic pulmonary fibrosis
led by Syndax is expected to begin in the fourth quarter of
2022.
For more information about AGAVE-201, visit
https://clinicaltrials.gov/ct2/show/NCT04710576
About Syndax Pharmaceuticals,
Inc.
Syndax Pharmaceuticals is a clinical stage biopharmaceutical
company developing an innovative pipeline of cancer therapies.
Highlights of the Company's pipeline include revumenib (SNDX-5613),
a highly selective inhibitor of the Menin–MLL binding interaction,
and axatilimab, a monoclonal antibody that blocks the colony
stimulating factor 1 (CSF-1) receptor, both currently in pivotal
trials. For more information, please visit www.syndax.com or follow
the Company on Twitter and LinkedIn.
About Incyte
Incyte is a Wilmington,
Delaware-based, global biopharmaceutical company focused on
finding solutions for serious unmet medical needs through the
discovery, development and commercialization of proprietary
therapeutics. For additional information on Incyte, please
visit Incyte.com and follow @Incyte.
Syndax Forward-Looking
Statements
This press release contains forward-looking statements within
the meaning of the Private Securities Litigation Reform Act of
1995. Words such as "may," "will," "expect," "plan," "anticipate,"
"estimate," "intend," "believe" and similar expressions (as well as
other words or expressions referencing future events, conditions or
circumstances) are intended to identify forward-looking statements.
These forward-looking statements are based on Syndax's expectations
and assumptions as of the date of this press release. Each of these
forward-looking statements involves risks and uncertainties. Actual
results may differ materially from these forward-looking
statements. Forward-looking statements contained in this press
release include, but are not limited to, statements about the
progress, timing, clinical development and scope of clinical
trials, the reporting of clinical data for Syndax's product
candidates, and the potential use of our product candidates to
treat various cancer indications and fibrotic diseases. Many
factors may cause differences between current expectations and
actual results, including: unexpected safety or efficacy data
observed during preclinical or clinical trials; clinical trial site
activation or enrollment rates that are lower than expected;
changes in expected or existing competition; changes in the
regulatory environment; the COVID-19 pandemic may disrupt our
business and that of the third parties on which we depend,
including delaying or otherwise disrupting our clinical trials and
preclinical studies, manufacturing and supply chain, or impairing
employee productivity; failure of Syndax's collaborators to support
or advance collaborations or product candidates; and unexpected
litigation or other disputes. Other factors that may cause Syndax's
actual results to differ from those expressed or implied in the
forward-looking statements in this press release are discussed in
Syndax's filings with the U.S. Securities and Exchange Commission,
including the "Risk Factors" sections contained therein. Except as
required by law, Syndax assumes no obligation to update any
forward-looking statements contained herein to reflect any change
in expectations, even as new information becomes available.
Incyte Forward-looking
Statements
Except for the historical information set forth herein, the
matters set forth in this press release, including statements
regarding the potential of axatilimab to treat patients with
chronic graft-versus-host disease or for any other indication, the
AGAVE-201 study and other clinical trials involving axatilimab,
contain predictions, estimates and other forward-looking
statements.
These forward-looking statements are based on Incyte's current
expectations and are subject to risks and uncertainties that may
cause actual results to differ materially, including unanticipated
developments in and risks related to: unanticipated delays; further
research and development and the results of clinical trials
possibly being unsuccessful or insufficient to meet applicable
regulatory standards or warrant continued development; the ability
to enroll sufficient numbers of subjects in clinical trials; the
effects of the COVID-19 pandemic and measures to address the
pandemic on Incyte's clinical trials, supply chain, other
third-party providers and development and discovery operations;
determinations made by regulatory authorities; Incyte's dependence
on its relationships with its collaboration partners; the efficacy
or safety of Incyte's products and the products of Incyte's
collaboration partners; the acceptance of Incyte's products and the
products of Incyte's collaboration partners in the marketplace;
market competition; sales, marketing, manufacturing and
distribution requirements; and other risks detailed from time to
time in Incyte's reports filed with the Securities and Exchange
Commission, including its annual report and its quarterly report on
Form 10-Q for the quarter ended September 30, 2022. Incyte
disclaims any intent or obligation to update these forward-looking
statements.
References
- SmartAnalyst 2020 SmartImmunology Insights chronic GVHD
report.
- Bachier, CR. et al. ASH annual meeting 2019; abstract #2109
Epidemiology and Real-World Treatment of Chronic Graft-Versus-Host
Disease Post Allogeneic Hematopoietic Cell Transplantation:
A U.S. Claims Analysis.
- Kantar 2020 GVHD Expert Interviews N=32 interviews.
Syndax Contact
Sharon Klahre
Syndax Pharmaceuticals, Inc.
sklahre@syndax.com
Tel 781.684.9827
Incyte
Contacts:
Media
Catalina
Loveman
cloveman@incyte.com
+1 302 498 6171
Investors
Christine Chiou
cchiou@incyte.com
+1 302 274 4773
SNDX-G
INCY-G
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SOURCE Syndax Pharmaceuticals, Inc.