Syndax Announces Positive Pivotal Topline Results from Relapsed or Refractory mNPM1 AML Cohort in AUGMENT-101 Trial of Revumenib
Syndax Pharmaceuticals (SNDX) announced positive topline results from the AUGMENT-101 trial of revumenib in relapsed/refractory mNPM1 AML patients. The trial met its primary endpoint with a 23% complete remission rate (p-value = 0.0014) and achieved a 47% overall response rate in a heavily pre-treated population. The safety profile was favorable, with only 5% of patients discontinuing due to treatment-related adverse events. The company plans to submit a supplemental New Drug Application (sNDA) in the first half of 2025, following anticipated FDA approval for KMT2Ar acute leukemia in Q4 2024.
Syndax Pharmaceuticals (SNDX) ha annunciato risultati positivi preliminari dal trial AUGMENT-101 di revumenib in pazienti con leucemia mieloide acuta (AML) relapsata/refrattaria mNPM1. Lo studio ha raggiunto il suo obiettivo primario con un tasso di remissione completa del 23% (p-value = 0.0014) e ha ottenuto un tasso di risposta globale del 47% in una popolazione fortemente pretrattata. Il profilo di sicurezza è stato favorevole, con solo il 5% dei pazienti che ha interrotto il trattamento a causa di eventi avversi correlati. La società prevede di presentare una domanda supplementare per un nuovo farmaco (sNDA) nella prima metà del 2025, in seguito all'attesa approvazione della FDA per la leucemia acuta KMT2Ar nel Q4 2024.
Syndax Pharmaceuticals (SNDX) anunció resultados positivos preliminares del ensayo AUGMENT-101 de revumenib en pacientes con leucemia mieloide aguda (LMA) mNPM1 en recaída/refractaria. El ensayo alcanzó su objetivo primario con una tasa de remisión completa del 23% (p-valor = 0.0014) y logró una tasa de respuesta global del 47% en una población que había sido tratada previamente de manera intensiva. El perfil de seguridad fue favorable, con solo un 5% de los pacientes interrumpiendo el tratamiento debido a eventos adversos relacionados. La compañía planea presentar una solicitud suplementaria de nuevo fármaco (sNDA) en la primera mitad de 2025, tras la anticipada aprobación de la FDA para la leucemia aguda KMT2Ar en el cuarto trimestre de 2024.
Syndax Pharmaceuticals (SNDX)는 재발/저항성 mNPM1 AML 환자를 대상으로 한 revumenib의 AUGMENT-101 시험에서 긍정적인 초기 결과를 발표했습니다. 이 시험은 23%의 완전 관해율 (p-값 = 0.0014)을 달성했고, 고도로 전처리된 집단에서 47%의 전체 반응률을 기록했습니다. 안전성 프로필은 favorable 하여, 치료 관련 부작용으로 인해 중단한 환자는 5%에 불과했습니다. 이 회사는 2025년 상반기에 추가 신약 신청서(sNDA)를 제출할 예정이며, 2024년 4분기에 KMT2Ar 급성 백혈병에 대한 FDA 승인을 기대하고 있습니다.
Syndax Pharmaceuticals (SNDX) a annoncé des résultats préliminaires positifs de l'essai AUGMENT-101 du revumenib chez des patients atteints de LAM mNPM1 en rechute/réfractaire. L'essai a atteint son objectif principal avec un taux de rémission complète de 23% (valeur p = 0.0014) et a obtenu un taux de réponse global de 47% dans une population fortement prétraitée. Le profil de sécurité était favorable, avec seulement 5% des patients interrompant le traitement en raison d'effets indésirables liés au traitement. La société prévoit de soumettre une demande de médicament nouveau supplémentaire (sNDA) au cours du premier semestre 2025, suite à l'approbation anticipée par la FDA pour la leucémie aiguë KMT2Ar au quatrième trimestre 2024.
Syndax Pharmaceuticals (SNDX) hat positive vorläufige Ergebnisse aus der AUGMENT-101-Studie mit Revumenib bei Patienten mit rezidivierender/refraktärer mNPM1 AML bekannt gegeben. Die Studie erreichte ihr primäres Ziel mit einer 23%igen vollständigen Remission (p-Wert = 0.0014) und erzielte eine 47%ige Gesamtansprechrate in einer stark vorbehandelten Population. Das Sicherheitsprofil war günstig, mit nur 5% der Patienten, die aufgrund behandlungsbedingter Nebenwirkungen abbrachen. Das Unternehmen plant, in der ersten Hälfte des Jahres 2025 einen ergänzenden Antrag auf Zulassung eines neuen Arzneimittels (sNDA) zu stellen, nach der erwarteten Genehmigung durch die FDA für KMT2Ar akute Leukämie im vierten Quartal 2024.
- Met primary endpoint with 23% complete remission rate (p-value = 0.0014)
- 47% overall response rate in heavily pre-treated population
- 64% of CR/CRh patients achieved MRD negative status
- Low discontinuation rate of 5% due to treatment-related adverse events
- 75% of patients previously treated with venetoclax showed response
- Median duration of CR/CRh responses was only 4.7 months
- 21% of patients experienced Grade ≥3 QTc prolongation
- 13% of patients experienced Grade ≥3 differentiation syndrome
Insights
The pivotal Phase 2 AUGMENT-101 trial results for revumenib represent a significant breakthrough in treating relapsed/refractory mNPM1 AML. The 23% complete remission rate (p=0.0014) and 47% overall response rate in heavily pretreated patients are particularly impressive, especially considering 75% had prior venetoclax exposure.
The safety profile is encouraging with only 5% discontinuation rate due to treatment-related adverse events. The 64% MRD negativity rate among CR/CRh achievers suggests deep responses, though the 4.7-month median duration of response warrants attention.
The planned sNDA filing in 1H25 could position revumenib as a vital treatment option for approximately 40% of AML patients with NPM1 mutations or KMT2A rearrangements, representing a significant market opportunity.
These results demonstrate meaningful clinical efficacy in a notoriously difficult-to-treat patient population. The 47% ORR in heavily pretreated patients is clinically significant, particularly given the options for R/R mNPM1 AML patients who have failed venetoclax therapy.
The manageable safety profile, including differentiation syndrome and QTc prolongation, aligns with expectations for this drug class. The ability for some patients to bridge to stem cell transplant (17% of responders) and resume treatment post-transplant adds significant clinical value.
The high rate of MRD negativity (64%) among complete responders suggests revumenib can achieve deep molecular responses, though longer follow-up will be needed to assess durability.
– Primary endpoint met with CR/CRh rate of
–
– Favorable safety and tolerability profile; only
– 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 –
The primary endpoint was met with a complete remission (CR) plus CR with partial hematological recovery (CRh) rate of
"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
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
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
"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
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
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
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
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
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.
FAQ
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