– Trial met its primary endpoint across all
cohorts with an overall response rate (ORR) of 74% at a dose of 0.3
mg/kg administered every two weeks –
– Data highlight durable response to
treatment. At the 0.3 mg/kg dose, 60% of patients who responded to
axatilimab were still responding at one year –
– Results continue to support
axatilimab's promising safety and efficacy profile, and reinforce
its potential as a first-in-class CSF-1R monoclonal antibody in
chronic graft-versus-host disease (GVHD) –
– Syndax and Incyte intend to file a Biologics
License Application (BLA) by year-end 2023; full dataset to be
presented at a future medical meeting –
– Syndax to host conference call today at
8:30 a.m. ET –
WALTHAM,
Mass. and WILMINGTON,
Del., July 24, 2023 /PRNewswire/ -- Syndax
Pharmaceuticals (Nasdaq: SNDX) and Incyte (Nasdaq: INCY) today
announced positive topline data from the pivotal AGAVE-201 trial of
axatilimab, an anti-CSF-1R antibody, in adult and pediatric
patients with chronic graft-versus-host disease (GVHD) following
two or more prior lines of therapy.
The trial achieved its primary endpoint across all cohorts, with
patients treated with axatilimab at doses of 0.3 mg/kg every two
weeks, 1.0 mg/kg every two weeks and 3.0 mg/kg every four weeks
demonstrating overall response rates (ORR) within the first six
months of treatment of 74%, 67% and 50%, respectively (95%
Confidence Interval [CI]: [63,83], [55,77] and [39,61],
respectively). Responses were achieved across key patient
subgroups, including those with prior exposure to ruxolitinib,
belumosudil and/or ibrutinib.
Based on these results, and pending agreement from the U.S. Food
and Drug Administration (FDA), Syndax and Incyte intend to submit a
Biologics License Application (BLA) to the FDA by year-end
2023.
"Today marks an important day not only for Syndax and Incyte,
but, more importantly, for patients suffering from chronic GVHD,"
said Michael A. Metzger, Chief
Executive Officer of Syndax. "Axatilimab is the first
investigational chronic GVHD treatment to target inflammation and
fibrosis through the inhibition of disease associated macrophages,
and the AGAVE-201 data demonstrates the potentially pronounced
impact this mechanism, alone or in combination with standard of
care therapies already available for the management of this
disease, may have on patients suffering from chronic GVHD. These
results underscore our belief that axatilimab could provide a
valuable and highly differentiated therapeutic option for this
devastating disease. We look forward to working with our partners
at Incyte as we move axatilimab towards regulatory filing. On
behalf of the entire Syndax team, I would like to thank the
patients, their caregivers and the investigators who made this
trial possible."
"The results from the AGAVE-201 study are extremely compelling
and underscore the potential benefits axatilimab may offer
appropriate patients facing the serious complications associated
with chronic GVHD," said Steven
Stein, M.D., Chief Medical Officer of Incyte. "At Incyte, we
remain committed to advancing our research and understanding of
this complex disease and will work closely with Syndax and
regulatory authorities to bring this innovative medicine to chronic
GVHD patients."
The AGAVE-201 pivotal study enrolled a total of 241 patients
across 121 sites in 16 countries. Patients enrolled in the trial
had received a median of four prior systemic therapies with 74%
having previously received ruxolitinib, 23% having previously
received belumosudil and 31% having previously received ibrutinib.
54% of these patients had at least four organs involved at baseline
including 45% with lung involvement.
Among responders treated with 0.3 mg/kg of axatilimab, 60% of
patients maintained a response at 12 months (measured from first
response to new systemic therapy or death, based on the Kaplan
Meier estimate). The median duration of response in this population
has not been reached. Additionally, in the 0.3 mg/kg group, 55% of
patients experienced a clinically meaningful improvement in
symptoms, as measured by at least a seven-point decrease in the
modified Lee chronic GVHD Symptom Scale score.
The most common adverse events were consistent with the
on-target effects of CSF-1R inhibition and with what was previously
observed with axatilimab treatment. In the overall population,
adverse events in greater than 20% of patients include an increase
in aspartate aminotransferase, blood creatine phosphokinase,
lipase, blood lactate dehydrogenase, alanine aminotransferase
and fatigue (n=239). Serious adverse events in the overall
population occurred in 101 (42.3%) patients, with 37 (15.5%)
patients experiencing adverse events leading to discontinuation of
study treatment. In the 0.3 mg/kg dose group (n=79), fatigue was
the only serious adverse event that occurred in greater than 20% of
patients. Serious adverse events in the 0.3 mg/kg group occurred in
30 (38%) patients, with five (6.3%) patients experiencing adverse
events leading to discontinuation of study treatment.
"Chronic GVHD is a very common complication post allogeneic
hematopoietic stem cell transplant that can have profound effects
on patient medical burden and quality of life. More effective
treatment options for this significant complication are desperately
needed," said Carrie Kitko, M.D.,
Medical Director of the Pediatric Stem Cell Transplant Program at
the Vanderbilt-Ingram Cancer Center. "I am highly encouraged by
these data which demonstrate robust responses in a heavily
pre-treated patient population. These findings further support that
axatilimab has the potential to provide a clinically meaningful
response for patients suffering from this morbid condition."
Conference Call and Webcast
Syndax will host a
conference call and webcast to discuss the results of the Phase 2
AGAVE-201 trial today, July 24, 2023
at 8:30 a.m. ET.
The live webcast may be accessed through the Events &
Presentations page in the Investors section of the Company's
website. Alternatively, the conference call may be accessed through
the following:
Conference ID: SNDXSPEC
Domestic Dial-in Number: 800-579-2543
International Dial-in Number: 785-424-1789
Live
webcast: https://www.veracast.com/webcasts/syndax/events/specconf.cfm
For those unable to participate in the conference call or
webcast, a replay will be available on the Investors section of the
Company's website at www.syndax.com approximately 24
hours after the conference call and will be available for 90 days
following the call.
About Chronic Graft-Versus-Host Disease
Chronic
graft-versus-host disease (GVHD), 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
tissue3.
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
chronic GVHD and IPF. Phase 1/2 data of Axatilimab in chronic GVHD
demonstrating its broad activity and tolerability was last
presented at the 63rd American Society of Hematology Annual Meeting
and data was published in the Journal of Clinical Oncology.
Axatilimab was granted Orphan Drug Designation by the U.S.
Food and Drug Administration for the treatment of patients
with chronic GVHD 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.
About AGAVE-201
The global Phase 2 AGAVE-201
dose-ranging trial evaluated the efficacy, safety, and tolerability
of axatilimab in 241 adult and pediatric patients with recurrent or
refractory active chronic GVHD whose disease had progressed after
two prior therapies. Patients were randomized to one of three
treatment groups that investigated a distinct dose of axatilimab
administered at 0.3 mg/kg every two weeks, 1 mg/kg every two weeks
or 3 mg/kg every four weeks. The trial's primary endpoint is the
proportion of patients in each dose group who achieved an objective
response as defined by 2014 NIH Consensus Criteria for chronic GVHD
by cycle 7 day 1. Secondary endpoints include duration of response,
percent reduction in daily steroids dose, organ specific response
rates and validated quality-of-life assessments using the Modified
Lee Symptom Scale.
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, a highly selective inhibitor of the
Menin–KMT2A binding interaction, and axatilimab,
a monoclonal antibody that blocks the colony stimulating factor 1
(CSF-1) receptor. 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, the potential filing of a BLA by year-end 2023, 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;
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 AGAVE-201
trial and the potential for axatilimab to become a treatment option
for chronic graft-versus-host disease, contain predictions,
estimates and other forward-looking statements.
These forward-looking statements are based on Incyte's current
expectations and 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;
determinations made by the U.S. FDA and other regulatory
authorities outside of the United
States; the efficacy or safety of Incyte and its partners'
products; the acceptance of Incyte and its partners' products 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 for
the year ended December 31, 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
sklahre@syndax.com
Tel 781.684.9827
Incyte
Contacts:
Media
Catalina Loveman
cloveman@incyte.com
Tel 302.498.6171
Investors
Greg Shertzer
gshertzer@incyte.com
Tel 302.498.4779
SNDX-G
INCY-G
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SOURCE Syndax Pharmaceuticals, Inc.