– Pivotal AUGMENT-101 trial met its primary
endpoint at interim analysis of patients with KMT2Ar AML and
ALL (p-value = 0.0036) –
– NDA filing for revumenib in R/R KMT2Ar acute leukemia is
being reviewed under RTOR; PDUFA action date of December 26,
2024 –
WALTHAM,
Mass., Aug. 12, 2024 /PRNewswire/ -- Syndax
Pharmaceuticals (Nasdaq: SNDX), a clinical stage biopharmaceutical
company developing an innovative pipeline of cancer therapies,
today announced that data from the pivotal Phase 2 portion of the
AUGMENT-101 trial of revumenib, a first-in-class menin inhibitor,
in adult and pediatric patients with relapsed/refractory (R/R)
KMT2A-rearranged (KMT2Ar) acute myeloid leukemia (AML) and acute
lymphoid leukemia (ALL) have been published in the Journal of
Clinical Oncology.
"Publication of the pivotal AUGMENT-101 dataset in KMT2Ar acute
leukemia allows for a broader dissemination of these important data
and highlights revumenib's impressive and consistent clinical
profile that has led to meaningful results for these advanced
patients," said Neil Gallagher, M.D., Ph.D., President, Head
of Research and Development at Syndax. "These data serve as the
foundation for the NDA filing that is currently being reviewed by
the FDA under its RTOR program. As we approach the potential FDA
approval of revumenib, we are actively preparing for a successful
commercial launch to enable us to deliver this important medicine
to patients in need."
"Despite an increased understanding of the mechanisms governing
development of KMT2Ar acute leukemia, no available therapies
adequately serve this population," said Ghayas C. Issa, M.D., Assistant Professor,
Department of Leukemia, Division of Cancer Medicine, The
University of Texas MD Anderson Cancer
Center. "The high rate of deep, MRD negative responses along with a
safety profile that supports prolonged time on therapy
and maintained remission post-stem cell transplant gives
me confidence that revumenib could serve as a paradigm-changing
treatment."
The FDA has granted Priority Review for the New Drug Application
(NDA) for revumenib for the treatment of adult and pediatric R/R
KMT2Ar acute leukemia. The NDA is being reviewed under
the FDA's Real-Time Oncology Review Program (RTOR) and
has a Prescription Drug User Fee Act (PDUFA) target action date of
December 26, 2024.
In March 2024, the Company announced the completion of
enrollment in the final AUGMENT-101 pivotal trial cohort in
patients with R/R mutant nucleophosmin (mNPM1) AML. Topline data is
expected in the fourth quarter of 2024 and could support a
supplemental NDA filing for revumenib in R/R mNPM1 AML in the first
half of 2025.
About the data
The publication entitled "Menin Inhibition With Revumenib for
KMT2A-Rearranged Relapsed or Refractory Acute Leukemia
(AUGMENT-101)" includes positive data from a total of 94 acute
leukemia patients with KMT2Ar in the pivotal trial as of the
July 2023 data cutoff, 57 of whom had
central confirmation of their KMT2Ar status, sufficient follow-up
and were in the efficacy analysis.
The AUGMENT-101 trial met its primary endpoint at the
protocol-defined interim analysis with a complete remission (CR) or
a CR with partial hematological recovery (CRh) rate of 23% (13/57;
95% confidence interval [CI]: [12.7, 35.8, one-sided p-value =
0.0036]) among the 57 efficacy evaluable patients in the KMT2Ar
acute leukemia population. The CR + CRh rate was 23% (10/44; 95%
CI: 11.5, 37.8) in adult patients and 23% in pediatric patients
(3/13; 95% CI: 5.0, 53.8). The median time to CR + CRh in the
overall efficacy-evaluable population was 1.9 months (range: 0.9,
4.6) and the CR + CRh responses were durable with a 6.4-month (95%
CI: 3.4, NR) median duration and 46% (6/13) remaining in response
at the time of data cutoff. Minimal residual disease (MRD) status
was assessed in 10 of the 13 patients who achieved a CR + CRh, 70%
(7/10) of whom were MRD negative.
In the efficacy evaluable patients, the overall response
rate1 was 63% (36/57; 95% CI: [49.3, 75.6]), and the
composite response rate (CRc) was 44% (25/57). MRD status was
assessed in 22 of the 25 patients who achieved a CRc, 68% (15/22)
of whom were MRD negative. Responses were observed in all major
subgroups, including across the number of prior treatments and
prior stem cell transplant, and across a broad age range with the
youngest responder aged 1 year and oldest aged 75 years. A total of
14 (39%) patients who achieved an overall response underwent HSCT,
eight of whom did not achieve a CR or CRh prior to transplant. Half
(7/14) of the patients who had an HSCT resumed revumenib treatment
post-transplant. Median overall survival at the time of data cutoff
was 8.0 months (95% CI: 4.1, 10.9).
Revumenib was well tolerated and the safety profile was
consistent with the Company's previously reported data. In the
pivotal AUGMENT-101 trial safety population (n=94),
treatment-emergent adverse events (TEAEs) of Grade ≥3 that occurred
in ≥10% of patients included febrile neutropenia (37%), neutropenia
(29%), thrombocytopenia (21%), anemia (18%), differentiation
syndrome (16%), QTc prolongation (14%), sepsis (12%), and
hypokalemia (11%). TEAEs leading to dose reduction or
discontinuation were low at 9.6% (9/94) and 12.8% (12/94) of
patients, respectively. Grade 3 DS was observed in 15% (14/94) of
patients while one patient (1%) experienced Grade 4 DS and no
patients experienced Grade 5 DS. No Grade 4 or 5 QTc events
occurred. There were no discontinuations related to DS, cytopenias
or QTc prolongation as of the July
2023 data cutoff.
About Revumenib
Revumenib is a potent, selective, small molecule inhibitor of
the menin-KMT2A binding interaction that is being developed for the
treatment of KMT2A-rearranged (KMT2Ar), also known as mixed lineage
leukemia rearranged or MLLr, acute leukemias including ALL and AML,
and mutant nucleophosmin (mNPM1) AML. Positive topline results from
the Phase 2 AUGMENT-101 trial in R/R KMT2Ar acute leukemia showing
the trial met its primary endpoint were presented at the 65th
American Society of Hematology Annual Meeting, and full data have
now been published in the Journal of Clinical Oncology.
Revumenib was granted Orphan Drug Designation for the treatment of
AML and ALL by the FDA and for the treatment of AML by the European
Commission, 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. Revumenib was granted
Breakthrough Therapy Designation by the FDA for the treatment of
adult and pediatric patients with R/R acute leukemia harboring a
KMT2A rearrangement.
About Syndax
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 menin inhibitor, 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 X (formerly
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 "anticipate," "believe," "could," "estimate,"
"expects," "intend," "may," "plan," "potential," "predict,"
"project," "should," "will," "would" or the negative or plural of
those terms, 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 its 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.
References
1 Overall response rate includes CR, CRh, CRp,
CRi, MLFS, and PR; Composite complete remission (CRc) includes CR,
CRh, CRp, and CRi
CR = Complete remission
CRh = Complete remission with partial hematologic recovery
CRp = Complete remission with incomplete platelet recovery
CRi = Complete remission with incomplete count recovery
MLFS = Morphologic leukemia-free state
PR = Partial response
Syndax Contact
Sharon Klahre
Syndax Pharmaceuticals, Inc.
sklahre@syndax.com
Tel 781.684.9827
SNDX-G
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SOURCE Syndax Pharmaceuticals, Inc.