-- Revumenib is the first and only
investigational treatment for R/R KMT2Ar acute leukemia to receive
Breakthrough Therapy Designation --
-- Designation is based on Phase 1 data from
the AUGMENT-101 trial that showed a 27% CR/CRh rate in KMT2A
patients treated at RP2D --
-- Company remains on track to submit an NDA
for revumenib by the end of 2023 with the potential for an
expedited approval with a broad indication --
WALTHAM,
Mass., Dec. 5, 2022 /PRNewswire/ -- Syndax
Pharmaceuticals, Inc. (Nasdaq: SNDX), a clinical-stage
biopharmaceutical company developing an innovative pipeline of
cancer therapies, today announced that the U.S. Food and Drug
Administration (FDA) has granted Breakthrough Therapy Designation
(BTD) for revumenib for the treatment of adult and pediatric
patients with relapsed or refractory (R/R) acute leukemia harboring
a KMT2A rearrangement (KMT2Ar). Revumenib is the Company's highly
selective, oral menin inhibitor.
"The Breakthrough Therapy Designation underscores revumenib's
potential as a first- and best-in-class therapy to meaningfully
change the treatment paradigm for patients with R/R KMT2Ar acute
leukemia, whether it presents clinically as acute myeloid leukemia
(AML) or acute lymphocytic leukemia (ALL), in adults or children,"
said Michael A. Metzger, Chief
Executive Officer. "Revumenib has the potential, if approved, to be
the first drug to address the significant unmet need in KMT2Ar
leukemia believed to occur in up to 10% of all acute
leukemias, including in approximately 80% of infant acute
leukemias. Syndax is committed to bringing revumenib to these
patients as quickly as possible and we look forward to working
collaboratively with the FDA to expedite a potential approval of
revumenib."
The BTD is supported by Phase 1 data from the AUGMENT-101 trial.
Ten of 37 patients (27%) with age and phenotype agnostic KMT2Ar
acute leukemia treated at doses meeting the protocol defined
criteria for the recommended Phase 2 dose (RP2D) and evaluable for
efficacy as of the March 2022 data
cutoff achieved a complete remission as measured by a CR/CRh.
Included in this analysis were patients treated in Arm A (226 and
276 mg q12 hours not receiving a strong CYP3A4 inhibitor) and Arm B
(113 and 163 mg q12 hours receiving a strong CYP3A4 inhibitor).
As previously announced, additional data from the Phase 1
portion of the AUGMENT-101 trial will be presented during two oral
sessions at the American Society of Hematology (ASH) Annual Meeting
on December 10, 2022. The abstracts
(Abstracts #63 and #376) describe data on the 60 patients with
R/R mutant NPM1 (n=14) or KMT2A rearranged (MLLr; n=46) acute
leukemia that were evaluable for efficacy as of the March 2022 data cutoff date. Additional analyses
from the trial that will be presented at the ASH Annual Meeting
indicate a 27% CR/CRh rate at doses meeting the protocol defined
criteria for the RP2D in all efficacy evaluable patients (13/48)
and in patients with an NPM1 mutation (3/11). There were no
discontinuations due to treatment-related adverse events.
The FDA grants BTD to expedite the development and regulatory
review of drugs that are intended for serious or life-threatening
conditions. The designation is based on preliminary clinical
evidence indicating that a drug may demonstrate substantial
improvement on at least one clinically significant endpoint over
available therapy. BTD affords all of the benefits of the fast
track program, eligibility for rolling review and potentially
priority review, and additional engagement to facilitate an
expedited development plan and regulatory review.
About Revumenib
Revumenib is a potent, selective, small molecule inhibitor of
the menin-MLL binding interaction that is being developed for the
treatment of KMT2A rearranged, also known as mixed lineage leukemia
rearranged or MLLr, acute leukemias including acute lymphoblastic
leukemia (ALL) and acute myeloid leukemia (AML), and NPM1 mutant
AML. Revumenib is currently being evaluated in several clinical
trials, including the Company's pivotal AUGMENT-101 Phase 1/2
open-label clinical trial for the treatment of relapsed/refractory
(R/R) acute leukemias. Robust clinical activity with durable
responses have been reported in the Phase 1 portion of AUGMENT-101.
Revumenib was granted Orphan Drug Designation by the U.S. Food
and Drug Administration (FDA) and European
Commission for the treatment of patients with AML, and Fast
Track designation by the FDA for the treatment of adult and
pediatric patients with R/R acute leukemias harboring a KMT2A
rearrangement or NPM1 mutation.
About KMT2A (MLL) Rearranged Acute Leukemia
Rearrangements of the KMT2A (mixed lineage leukemia or MLL) gene
give rise to KMT2Ar acute leukemia known to have a poor prognosis,
with less than 25% of adult patients surviving past five years.
KMT2A genes produce fusion proteins that require interaction with
the protein called menin to drive leukemic cancer growth.
Disruption of the menin-KMT2Ar interaction has been shown to halt
the growth of KMT2Ar leukemic cells.
KMT2Ar acute leukemia can phenotypically appear as AML,
ALL, or mixed phenotype acute leukemia (MPAL) and is routinely
diagnosed through currently available cytogenetic or molecular
diagnostic techniques. The median overall survival (OS) after
standard of care first-line treatment, including intensive
chemotherapy and transplant, is less than 1 year and the majority
of patients suffer relapse within 5 years. Most R/R patients
treated with second-line therapy relapse within the first year.
With third line treatment or beyond, only a small percentage of
patients achieve complete remission (CR), and the median OS is less
than 3 months.
About AUGMENT-101
AUGMENT-101 is a Phase 1/2 open-label trial designed to evaluate
the safety, tolerability, pharmacokinetics, and efficacy of orally
administered revumenib. The Phase 1 dose escalation portion of
AUGMENT-101 was separated into two cohorts based on concomitant
treatment with a strong CYP3A4 inhibitor. Arm A enrolled patients
not receiving a strong CYP3A4 inhibitor, while Arm B enrolled
patients receiving a strong CYP3A4 inhibitor. The Phase 2 pivotal
portion of AUGMENT-101 is currently underway. Patients will be
enrolled across each of the following trial populations: patients
with NPM1 mutant AML, patients with KMT2Ar (MLLr) AML, and patients
with KMT2Ar (MLLr) ALL. Discussions with the FDA have confirmed
that AUGMENT-101 may potentially serve as the basis for regulatory
filings in each patient population. The primary endpoint for each
of the trials will be efficacy as measured by complete remission
rate (CR + CRh), with key secondary endpoints including duration of
response (DOR) and overall survival (OS).
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.
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 progress of regulatory submissions and approvals,
including the impact of Breakthrough Therapy Designation on the
timeline for approval of revumenib, and the potential use of
Syndax's 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 impact of macroeconomic
conditions (such as COVID-19 pandemic, the Russia-Ukraine war, inflation, among others) on
Syndax's business and that of the third parties on which Syndax
depends, including delaying or otherwise disrupting Syndax's
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.
Syndax Contact
Sharon Klahre
Syndax Pharmaceuticals, Inc.
sklahre@syndax.com
Tel 781.684.9827
SNDX-G
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SOURCE Syndax Pharmaceuticals, Inc.