“ 82% ORR (27 of 33 pts) and 48% CR/CRh (16 of 33 pts) in SAVE trial learning revumenib together with venetoclax and decitabine/cedazuridine in R/R AML “
“ 64% ORR (62 of 97 pts) and 23% CR/CRh (22 of 97 pts) with excessive charges of MRD negativity and skill to proceed to HSCT in expanded dataset of Ph 2 R/R KMT2Ar acute leukemia sufferers in AUGMENT-101 “
“ Responses have been speedy, sturdy and noticed throughout all main subgroups in expanded dataset of
Ph 2 R/R KMT2Ar acute leukemia sufferers in AUGMENT-101 “
“ Newest knowledge spotlight the compelling medical profile of revumenib and help development into mixture trials within the frontline setting “
“On the heels of the latest approval of Revuforj for R/R acute leukemia with a KMT2A translocation, we’re excited to current medical knowledge highlighting the constant efficacy and favorable tolerability of this first-in-class remedy, as each a single-agent and together with commonplace of care, in sufferers with mNPM1 and KMT2Ar acute leukemia,” mentioned
Overview of Revumenib Information Introduced in
Outcomes from Part 1/2 SAVE Trial of Revumenib in Mixture with Venetoclax and Decitabine/Cedazuridine in R/R AML
The Part 1/2 SAVE trial is an investigator-sponsored trial testing an all-oral routine of revumenib, venetoclax and the hypomethylating agent (HMA) ASTX727 (decitabine/cedazuridine) in pediatric and grownup sufferers with R/R acute myeloid leukemia (AML) or mixed-lineage acute leukemia (MPAL) harboring both KMT2Ar, NUP98r or mNPM1 alterations. Within the beforehand introduced ASH summary, knowledge from 26 sufferers within the SAVE trial have been reported (knowledge cutoff [DCO]: July 2024).
Through the oral session on the ASH assembly, knowledge from 33 sufferers have been introduced (DCO:
The all-oral mixture resulted in excessive charges of remission in sufferers with KMT2Ar, mNPM1, and NUP98r with an general response price (ORR)1 of 82% (27/33) and a CR/CRh price of 48% (16/33). In sufferers with minimal residual illness (MRD) standing accessible, 65% (17/26) who achieved a response have been MRD destructive, and amongst sufferers who achieved a CR/CRh response, 88% (14/16) have been MRD destructive. 39% (13/33) of sufferers proceeded to HSCT following this mix, with 54% (7/13) of sufferers resuming revumenib post-HSCT.
With a median follow-up of 9.3 months (N=33), the 6-month general survival (OS) was 68% (95% CI: 47%, 80%); median OS was not reached. The median length of CR/CRh response was additionally not reached.
The mixture was typically properly tolerated on this inhabitants. The commonest (>20%) Grade 3 or greater treatment-emergent antagonistic occasions (TEAEs) have been febrile neutropenia (33%) and lung an infection (33%). Grade 3 treatment-emergent differentiation syndrome (DS) was noticed in a single affected person (3%), with no Grade 4 or Grade 5 occasions. Grade 3 treatment-emergent QTc prolongation was noticed in two sufferers (6%) and Grade 4 was noticed in a single affected person (3%) with no Grade 5 occasions.
“The newest SAVE knowledge present excessive efficacy and the power to mix revumenib with venetoclax and hypomethylating brokers, which highlights the potential for this mix to grow to be a remedy for sufferers with acute leukemias which can be inclined to menin inhibition,” mentioned
Information from Part 2 Portion of the AUGMENT-101 Trial of Revumenib in R/R KMT2Ar Acute Leukemia
A bigger knowledge set with longer follow-up knowledge (DCO:
As described within the beforehand introduced ASH summary, the CR+CRh price was 23% (22/97), CRc was 42% (41/97), and ORR was 64% (62/97) among the many 97 efficacy evaluable sufferers. In sufferers with MRD outcomes accessible, 61% (11/18) of CR/CRh responders and 58% (21/36) of CRc responders achieved MRD negativity. Of the 62 sufferers who achieved ORR, 34% (21/62) proceeded to HSCT and 9 resumed revumenib post-HSCT.
Through the oral session on the ASH assembly, the Firm introduced further knowledge from this bigger knowledge set displaying that responses have been noticed throughout all main subgroups, together with closely pretreated sufferers, sufferers with prior venetoclax publicity, and sufferers of all ages. The up to date analyses additionally present that of the 21 responders who proceeded to HSCT, 67% (14/21) went to transplant in CRc [38% (8/21) in CR/CRh and 29% (6/21) in CRp/CRi] and 33% (7/21) went to transplant in MLFS. Of the sufferers who proceeded to transplant in CRc and had MRD outcomes accessible, 82% (9/11) have been MRD destructive.
Time to response was speedy with a median time to ORR of 1.0 months (vary: 0.9-3.1) and median time to CR/CRh of two.0 months (vary: 0.9-4.6). As beforehand reported, the median length of CR/CRh was 6.4 months among the many 22 CR/CRh responders. Of observe, with seven months of further follow-up, the median length of CR/CRh prolonged to 13 months among the many 13 CR/CRh responders included within the interim evaluation introduced on the ASH Annual Assembly in 2023.
On this bigger knowledge set, which incorporates 116 sufferers within the security inhabitants, revumenib was typically properly tolerated and the protection profile was in line with the Firm’s beforehand reported knowledge. Remedy-related antagonistic occasions (TRAEs) and treatment-emergent antagonistic occasions (TEAEs) resulting in remedy discontinuation have been low at 5% (6/116) and 14% (16/116), respectively. The commonest Grade 3 or greater TEAEs have been in line with beforehand reported knowledge. Grade 3 treatment-emergent DS was noticed in 14% (16/116) of sufferers and one affected person (1%) skilled a Grade 4 DS. Grade 3 treatment-emergent QTc prolongation was noticed in 13% (15/116) of sufferers, with no Grade 4 or Grade 5 occasions. No sufferers discontinued remedy attributable to differentiation syndrome, QTc prolongation, or cytopenias.
Preliminary Outcomes from INTERCEPT Platform Trial of Revumenib as Pre-Emptive Remedy for MRD Constructive AML
INTERCEPT is an investigator-sponsored platform trial evaluating using novel therapies, together with revumenib, to focus on MRD and early relapse in AML. This proof-of-concept trial is exploring whether or not concentrating on MRD in sufferers with AML could also be an efficient strategy to sustaining sufferers in first or second remission.
As of the most recent knowledge cutoff, 14 sufferers with MRD relapse (13 with mNPM1 and one with KMT2Ar) have been enrolled within the security cohort and acquired revumenib. The median age was 56 years; 12 have been in first remission and two have been in second remission. Previous to beginning revumenib remedy, two sufferers acquired venetoclax-based remedy and 12 acquired prior intensive chemotherapy-based remedy as their frontline remedy. Within the security cohort (N=14), the most typical (>10%) Grade 3 or greater TEAEs have been neutropenia, thrombocytopenia, and QTc interval prolongation. There have been no stories of DS, and no Grade 5 occasions.
Among the many 11 efficacy evaluable mNPM1 sufferers who acquired revumenib, 54% (6/11) sufferers had MRD discount at any time, together with 36% (4/11) who achieved MRD negativity. These preliminary knowledge help the additional analysis of revumenib as a novel strategy to concentrating on MRD relapse.
Copies of the ASH displays can be found within the Publications and Assembly Displays part of Syndax’s web site.
Syndax Company Occasion
Information introduced by the Firm on the 66th ASH Annual Assembly from each the Revuforj (revumenib) and Niktimvo (axatilimab-csfr) medical applications will likely be highlighted on the Firm’s investor occasion on
For these unable to take part within the convention name or webcast for the occasion, a replay will likely be accessible on the Buyers part of the Firm’s web site at www.syndax.com for a restricted time.
About Revuforj ® (revumenib)
Revuforj (revumenib) is an oral, first-in-class menin inhibitor that’s FDA permitted for the remedy of relapsed or refractory (R/R) acute leukemia with a lysine methyltransferase 2A gene (KMT2A) translocation in grownup and pediatric sufferers one 12 months and older.
Revumenib is in improvement for the remedy of R/R acute myeloid leukemia (AML) with a nucleophosmin 1 mutation (mNPM1). Constructive pivotal knowledge from the AUGMENT-101 trial on this inhabitants with revumenib as a monotherapy have been just lately reported. The Firm expects to file a supplemental NDA submitting for revumenib in R/R mNPM1 AML within the first half of 2025. Moreover, a number of trials of revumenib together with standard-of-care brokers in mNPM1 AML or KMT2A-rearranged acute leukemia are ongoing throughout the remedy panorama, together with in newly recognized sufferers.
Revumenib was beforehand granted Orphan Drug Designation for the remedy of AML, ALL and acute leukemias of ambiguous lineage (ALAL) by the
IMPORTANT SAFETY INFORMATION
WARNING: DIFFERENTIATION SYNDROME
Differentiation syndrome, which could be deadly, has occurred with Revuforj. Indicators and signs might embody fever, dyspnea, hypoxia, pulmonary infiltrates, pleural or pericardial effusions, speedy weight achieve or peripheral edema, hypotension, and renal dysfunction. If differentiation syndrome is suspected, instantly provoke corticosteroid remedy and hemodynamic monitoring till symptom decision.
WARNINGS AND PRECAUTIONS
Differentiation syndrome: Revuforj could cause deadly or life-threatening differentiation syndrome (DS). Signs of DS, together with these seen in sufferers handled with Revuforj, embody fever, dyspnea, hypoxia, peripheral edema, pleuropericardial effusion, acute renal failure, and/or hypotension. In medical trials, DS occurred in 39 (29%) of 135 sufferers handled with Revuforj. DS was Grade 3 or 4 in 13% of sufferers and deadly in a single. The median time to onset was 10 days (vary 3-41 days). Some sufferers skilled greater than 1 DS occasion. Remedy interruption was required for 7% of sufferers, and remedy was withdrawn for 1%.
Cut back the white blood cell depend to lower than 25 Gi/L previous to beginning Revuforj. If DS is suspected, instantly provoke remedy with systemic corticosteroids (e.g., dexamethasone 10-mg IV each 12 hours in adults or dexamethasone 0.25-mg/kg/dose IV each 12 hours in pediatric sufferers weighing lower than 40 kg) for no less than 3 days and till decision of indicators and signs. Institute supportive measures and hemodynamic monitoring till enchancment. Interrupt Revuforj if extreme indicators and/or signs persist for greater than 48 hours after initiation of systemic corticosteroids, or earlier if life-threatening signs happen akin to pulmonary signs requiring ventilator help. Restart steroids promptly if DS recurs after tapering corticosteroids.
QTc interval prolongation: Within the medical trials, QTc interval prolongation was reported as an antagonistic response in 39 (29%) of 135 sufferers handled with Revuforj. QTc interval prolongation was Grade 3 in 12% of sufferers. The guts-rate corrected QT interval (utilizing Fridericia’s technique) (QTcF) was higher than 500 msec in 8%, and the rise from baseline QTcF was higher than 60 msec in 18%. Revuforj dose discount was required for five% of sufferers attributable to QTc interval prolongation. QTc prolongation occurred in 16% of the 31 sufferers lower than 17 years previous, 33% of the 88 sufferers 17 years to lower than 65 years previous, and in 50% of the 16 sufferers 65 years or older.
Right electrolyte abnormalities, together with hypokalemia and hypomagnesemia, previous to remedy with Revuforj. Carry out an electrocardiogram (ECG) previous to initiation of Revuforj, and don’t provoke Revuforj in sufferers with QTcF >450 msec. Carry out an ECG a minimum of as soon as weekly for the primary 4 weeks and a minimum of month-to-month thereafter. In sufferers with congenital lengthy QTc syndrome, congestive coronary heart failure, electrolyte abnormalities, or those that are taking drugs identified to lengthen the QTc interval, extra frequent ECG monitoring could also be needed. Concomitant use with medicine identified to lengthen the QTc interval might enhance the danger of QTc interval prolongation.
- Interrupt Revuforj if QTcF will increase >480 msec and
- Interrupt Revuforj if QTcF will increase >500 msec or by >60 msec from baseline, and restart Revuforj twice every day on the lower-dose degree after the QTcF interval returns to ‰¤480 msec
- Completely discontinue Revuforj in sufferers with ventricular arrhythmias and in those that develop QTc interval prolongation with indicators or signs of life-threatening arrhythmia.
Embryo-fetal toxicity: Revuforj could cause fetal hurt when administered to a pregnant girl. Advise pregnant girls of the potential danger to a fetus. Advise females of reproductive potential and males with feminine companions of reproductive potential to make use of efficient contraception throughout remedy with Revuforj and for 4 months after the final dose of Revuforj.
ADVERSE REACTIONS
Deadly antagonistic reactions occurred in 4 (3%) sufferers who acquired Revuforj, together with 2 with differentiation syndrome, 1 with hemorrhage, and 1 with sudden demise.
Severe antagonistic reactions have been reported in 99 (73%) sufferers. Essentially the most frequent severe antagonistic reactions ( ‰¥5%) have been an infection (24%), febrile neutropenia (19%), bacterial an infection (17%), differentiation syndrome (12%), hemorrhage (9%), and thrombosis (5%).
Essentially the most widespread antagonistic reactions ( ‰¥20%) together with laboratory abnormalities, have been hemorrhage (53%), nausea (51%), phosphate elevated (50%), musculoskeletal ache (42%), an infection (41%), aspartate aminotransferase elevated (37%), febrile neutropenia (35%), alanine aminotransferase elevated (33%), parathyroid hormone intact elevated (33%), bacterial an infection (31%), diarrhea (30%), differentiation syndrome (29%), electrocardiogram QT extended (29%), phosphate decreased (25%), triglycerides elevated (25%), potassium decreased (24%), decreased urge for food (24%), constipation (23%), edema (23%), viral an infection (23%), fatigue (22%), and alkaline phosphatase elevated (21%).
DRUG INTERACTIONS
Drug interactions can happen when Revuforj is concomitantly used with:
- Sturdy CYP3A4 inhibitors: scale back Revuforj dose
- Sturdy or reasonable CYP3A4 inducers: keep away from concomitant use with Revuforj
- QTc-prolonging medicine: keep away from concomitant use with Revuforj. If concomitant use is unavoidable, acquire ECGs when initiating, throughout concomitant use, and as clinically indicated. Withhold Revuforj if the QTc interval is >480 msec. Restart Revuforj after the QTc interval returns to ‰¤480 msec.
SPECIFIC POPULATIONS
Lactation: advise lactating girls to not breastfeed throughout remedy with Revuforj and for 1 week after the final dose.
Being pregnant and testing: Revuforj could cause fetal hurt when administered to a pregnant girl. Confirm being pregnant standing in females of reproductive potential inside 7 days previous to initiating Revuforj.
Pediatric: monitor bone progress and improvement in pediatric sufferers.
Geriatric: in comparison with youthful sufferers, the incidences of QTc prolongation and edema have been greater in sufferers 65 years and older.
Infertility: primarily based on findings in animals, Revuforj might impair fertility. The results on fertility have been reversible.
To report SUSPECTED ADVERSE REACTIONS, contact Syndax Prescribed drugs at 1-888-539-3REV or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Please see Full Prescribing Data, together with BOXED WARNING.
About KMT2A-Rearranged Acute Leukemia
Rearrangements of the KMT2A gene (KMT2Ar) give rise to an aggressive type of acute leukemia that’s related to a really poor prognosis and excessive relapse charges. It’s estimated that greater than 95% of sufferers with KMT2Ar acute leukemia have a KMT2A translocation, a sort of rearrangement that happens when a part of one chromosome breaks and fuses to a unique chromosome.
In KMT2Ar acute leukemias, binding of KMT2A fusion proteins with the protein referred to as menin drives the activation of a leukemogenic transcriptional pathway. Inhibition of the menin-KMT2A interplay has been proven to change the transcription of a number of genes together with differentiation markers. KMT2Ar AML and ALL have a speedy onset and fast development that makes early identification of a KMT2A rearrangement important. It’s routinely recognized by means of at the moment accessible cytogenetic or molecular diagnostic strategies.
About Mutant NPM1 (mNPM1) Acute Myeloid Leukemia (AML)
Mutations within the NPM1 gene are the most typical genetic alteration in grownup AML and are noticed in roughly 30% of circumstances. Sufferers with relapsed or refractory mNPM1 AML have a poor prognosis and excessive unmet want. Much like KMT2A-rearranged acute leukemia, mNPM1 AML is extremely depending on the expression of particular developmental genes proven to be negatively impacted by inhibitors of the menin-KMT2A interplay. mNPM1 AML is routinely recognized by means of at the moment accessible screening strategies. There are at the moment no permitted focused therapies for mNPM1 AML.
About Syndax
Syndax Prescribed drugs is a commercial-stage biopharmaceutical firm growing an modern pipeline of most cancers therapies. Highlights of the Firm’s pipeline embody Revuforj ® (revumenib), an FDA-approved menin inhibitor, and Niktimvo™ (axatilimab-csfr), an FDA-approved monoclonal antibody that blocks the colony stimulating issue 1 (CSF-1) receptor. Fueled by our dedication to reimagining most cancers care, Syndax is working to unlock the complete potential of its pipeline and is conducting a number of medical trials throughout the continuum of remedy. For extra data, please go to www.syndax.com/ or comply with the Firm on X (previously Twitter) and LinkedIn.
Ahead-Trying Statements
This press launch incorporates forward-looking statements throughout the that means of the Non-public Securities Litigation Reform Act of 1995. Phrases akin to “anticipate,” “consider,” “may,” “estimate,” “expects,” “intend,” “might,” “plan,” “potential,” “predict,” “venture,” “ought to,” “will,” “would” or the destructive or plural of these phrases, and comparable expressions (in addition to different phrases or expressions referencing future occasions, circumstances or circumstances) are meant to establish forward-looking statements. These forward-looking statements are primarily based on Syndax’s expectations and assumptions as of the date of this press launch. Every of those forward-looking statements includes dangers and uncertainties. Precise outcomes might differ materially from these forward-looking statements. Ahead-looking statements contained on this press launch embody, however are usually not restricted to, statements in regards to the progress, timing, medical improvement and scope of medical trials, the reporting of medical knowledge for Syndax’s product candidates, the acceptance of Syndax and its companions’ merchandise within the market, gross sales, advertising and marketing, manufacturing and distribution necessities, and the potential use of its product candidates to deal with varied most cancers indications and fibrotic illnesses. Many elements might trigger variations between present expectations and precise outcomes, together with: sudden security or efficacy knowledge noticed throughout preclinical or medical trials; medical trial web site activation or enrollment charges which can be decrease than anticipated; modifications to Revuforj’s business availability, modifications in anticipated or present competitors; modifications within the regulatory atmosphere; failure of Syndax’s collaborators to help or advance collaborations or product candidates; and sudden litigation or different disputes. Different elements that will trigger Syndax’s precise outcomes to vary from these expressed or implied within the forward-looking statements on this press launch are mentioned in Syndax’s filings with the U.S. Securities and Trade Fee, together with the “Danger Components” sections contained therein. Besides as required by regulation, Syndax assumes no obligation to replace any forward-looking statements contained herein to mirror any change in expectations, whilst new data turns into accessible.
References
1. General response price (ORR) contains CR, CRh, CRp, CRi, MLFS, and PR; Composite full remission (CRc) contains CR, CRh, CRp, and CRi.
CR = Full remission
CRh = Full remission with partial hematologic restoration
CRp = Full remission with incomplete platelet restoration
CRi = Full remission with incomplete depend restoration
MLFS = Morphologic leukemia-free state
PR = Partial response
Syndax Contact
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