– Primary
endpoint met with CR/CRh rate of 23% in pivotal Ph 2 cohort of R/R
mNPM1 AML patients (p-value = 0.0014) –
– 47% (30/64)
ORR in a heavily pre-treated population, including 75% with prior
venetoclax exposure in the efficacy population –
– Favorable
safety and tolerability profile; only 5% of patients discontinued
due to treatment-related adverse events –
– Results
highlight consistency of revumenib's compelling clinical profile
–
– sNDA filing in
R/R mNPM1 AML expected in 1H25, pending anticipated FDA approval of
revumenib in R/R KMT2Ar acute leukemia in 4Q24 –
– Syndax to host
a conference call today at 8:00 am ET
–
WALTHAM,
Mass., Nov. 12, 2024 /PRNewswire/ -- Syndax
Pharmaceuticals (Nasdaq: SNDX), a commercial-stage
biopharmaceutical company developing an innovative pipeline of
cancer therapies, today announced positive topline results from the
relapsed or refractory (R/R) mutant NPM1 (mNPM1) acute myeloid
leukemia (AML) cohort in the pivotal Phase 2 portion of the
AUGMENT-101 trial of revumenib, an oral, small molecule menin
inhibitor.
The primary endpoint was met with a complete remission (CR) plus
CR with partial hematological recovery (CRh) rate of 23% (15/64;
95% confidence interval [CI]: 14%, 36%; one-sided p-value =0.0014)
among the efficacy evaluable adults with R/R mNPM1 AML in the Phase
2 portion of the AUGMENT-101 trial. Among the patients who achieved
CR/CRh, 12 patients had a CR and three had a CRh. The observed
median duration of CR/CRh responses was 4.7 months (95% CI: 1.2,
8.2) at the time of the data cutoff with three patients remaining
in response. Minimal residual disease (MRD) status was assessed in
14 of 15 patients who achieved CR/CRh, 64% (9/14) of whom were MRD
negative. The overall response rate (ORR)1 was 47%
(30/64; 95% CI: 34%, 60%). 17% (5/30) of patients who achieved an
overall response underwent hematopoietic stem cell transplant
(HSCT) following treatment with revumenib, with three resuming
revumenib therapy post-transplant.
"We are thrilled to report positive pivotal data in R/R mNPM1
AML patients treated with revumenib, which has shown compelling and
notably consistent results across treatment settings for both mNPM1
AML and KMT2A-rearranged acute leukemias," said Michael A. Metzger, Chief Executive Officer of
Syndax. "With the anticipated FDA approval of revumenib for the
treatment of R/R KMT2A-rearranged acute leukemias this quarter, and
this second positive pivotal data readout, we are well-positioned
to meaningfully impact the estimated 40% of AML patients with these
two genetic alterations."
The AUGMENT-101 Phase 2 protocol-defined efficacy evaluable
population included 64 adult patients with R/R mNPM1 AML. The
median age was 65 (range: 19, 84). Patients were heavily
pretreated, with 36% having received three or more prior lines of
therapy (median prior lines: 2) and 75% of patients previously
treated with venetoclax.
The safety population included 84 adult and pediatric patients
with R/R mNPM1 AML in the Phase 2 portion of the AUGMENT-101 trial.
The safety profile observed with revumenib in this population was
consistent with previously reported data. Treatment-related adverse
events (TRAEs) leading to treatment discontinuations were 5%
(4/84). TRAEs of Grade ≥3 in more than 10% of patients included:
QTc prolongation (21%), anemia (14%), febrile neutropenia (13%),
differentiation syndrome (13%), and platelet count decreased (11%).
Grade 3 treatment-related DS was observed in 11% (9/84) of patients
while 2% (2/84) experienced Grade 4 DS and no patients experienced
Grade 5. Grade 3 treatment-related QTc prolongation was observed in
19% (16/84) of patients while 2% (2/84) experienced Grade 4 QTc
prolongation and no patients experienced Grade 5.
"Relapsed or refractory mNPM1 AML is a very challenging disease
with a poor prognosis and an urgent need for new treatments," said
Eytan M. Stein, M.D., Chief,
Leukemia Service, Memorial Sloan Kettering Cancer Center. "The
positive results for revumenib in this heavily pre-treated
population, which included more than 75% who previously failed
venetoclax, are very encouraging. In particular, the robust rates
of overall response, including deep molecular remissions and low
discontinuation rates, highlight the tremendous promise of
revumenib in the treatment of R/R mNPM1 AML patients."
Revumenib Near-Term Milestones
The Company has several trials of revumenib ongoing across the
treatment landscape in mNPM1 and KMT2A-rearranged (KMT2Ar) acute
leukemias. In addition to the clinical trials that Syndax is
conducting, the Company is working with cooperative groups and key
investigators to further elucidate the potential clinical benefit
of revumenib. Syndax expects to achieve the following upcoming
revumenib milestones:
- Receive FDA approval for treatment of R/R KMT2Ar acute
leukemias in the fourth quarter of 2024.
- Present data in KMT2Ar and mNPM1 acute leukemias at the
66th American Society of Hematology (ASH) Annual Meeting
in December 2024.
- Initiate a pivotal combination trial with
venetoclax/azacitidine in newly diagnosed mNPM1 AML or KMT2Ar acute
leukemias by year-end 2024.
- Publish pivotal AUGMENT-101 results in R/R mNPM1 AML patients
and present results at a medical conference in the first half of
2025.
- Submit a supplemental NDA (sNDA) for treatment of R/R mNPM1 AML
in the first half of 2025.
Conference Call and Webcast
Syndax will host a
conference call and webcast to discuss the results of the
AUGMENT-101 trial in R/R mNPM1 AML today, November 12, 2024, at 8:00
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: Syndax Conference Call 1
Domestic Dial-in Number: 800-590-8290
International Dial-in Number: 240-690-8800
Live webcast:
https://www.veracast.com/webcasts/syndax/events/specialconf1.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 Revumenib
Revumenib is an oral, 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 acute lymphoid leukemia (ALL) and acute myeloid leukemia
(AML), and mutant NPM1 AML. The Journal of Clinical Oncology
published results from the Phase 2 AUGMENT-101 trial of revumenib
in R/R KMT2Ar acute leukemia showing the trial met its primary
endpoint.
Revumenib was previously granted Orphan Drug Designation for the
treatment of AML, ALL and acute leukemias of ambiguous lineage
(ALAL) by the U.S. FDA and for the treatment of AML by the European
Commission. The U.S. FDA also granted Fast Track designation to
revumenib for the treatment of adult and pediatric patients with
R/R acute leukemias harboring a KMT2A rearrangement or NPM1
mutation and Breakthrough Therapy Designation for the treatment of
adult and pediatric patients with R/R acute leukemia harboring a
KMT2A rearrangement.
About the Phase 1/2 AUGMENT-101 Trial
AUGMENT-101 an
open-label, multi-center trial evaluating the safety, tolerability,
pharmacokinetics, and efficacy of revumenib that consists of a dose
escalation part and an expansion part. In the dose escalation
part, a revumenib dose with and without a strong CYP3A4 inhibitor
was identified. The expansion part was designed to evaluate
revumenib in patients with relapsed or refractory (R/R) KMT2Ar AML,
patients with KMT2Ar ALL, and patients with mutant NPM1 (mNPM1)
AML. The primary endpoint for each of the cohorts is efficacy
as measured by the rate of complete remission (CR) plus CR with
partial hematologic recovery (CRh) and short- and long-term safety
and tolerability, with secondary endpoints including duration of
response (DOR) and overall survival (OS).
More information can be found on
www.clinicaltrials.gov (NCT04065399).
Positive data from the KMT2Ar AML and ALL patients in the trial
supported a New Drug Application (NDA) filing for revumenib in R/R
KMT2Ar acute leukemia, which is currently under review by the U.S.
FDA with a PDUFA action date of December 26,
2024. Positive data from the mNPM1 AML patients in the trial
are expected to support an sNDA filing in the first half of
2025.
About Mutant NPM1 (mNPM1) Acute Myeloid Leukemia
(AML)
Mutations in the NPM1 gene are the most common genetic
alteration in adult AML and are observed in approximately 30% of
cases. Patients with relapsed or refractory mNPM1 AML have a poor
prognosis and high unmet need. Similar to KMT2A-rearranged acute
leukemia, mNPM1 AML is highly dependent on the expression of
specific developmental genes shown to be negatively impacted by
inhibitors of the menin-KMT2A interaction. mNPM1 AML is routinely
diagnosed through currently available screening techniques. There
are currently no approved targeted therapies for mNPM1 AML.
About Syndax
Syndax Pharmaceuticals is a
commercial-stage biopharmaceutical company developing an innovative
pipeline of cancer therapies. Highlights of the Company's
pipeline include revumenib, a selective menin inhibitor, and
Niktimvo™ (axatilimab-csfr), an FDA-approved monoclonal antibody
that blocks the colony stimulating factor 1 (CSF-1) receptor.
Fueled by our commitment to reimagining cancer care, Syndax is
working to unlock the full potential of its pipeline and is
conducting several clinical trials across the continuum of
treatment. 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 "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 acceptance of Syndax and its partners' products in
the marketplace, sales, marketing, manufacturing and distribution
requirements, 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.
References
- Overall response rate (ORR) 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
- Issa G., et al. Clinical outcomes associated with NPM1
mutations in patients with relapsed or refractory AML. Blood Adv.
2023; 7(6):933-942.
Syndax Contact
Sharon Klahre
Syndax Pharmaceuticals, Inc.
sklahre@syndax.com
Tel 781.684.9827
SNDX-G
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SOURCE Syndax Pharmaceuticals, Inc.