Syndax Announces Publication in the Journal of Clinical Oncology of Data from the Pivotal AUGMENT-101 Trial of Revumenib in Relapsed/Refractory KMT2Ar Acute Leukemia

Rhea-AI Summary

Syndax Pharmaceuticals (NASDAQ: SNDX) announced the publication of data from the pivotal AUGMENT-101 trial of revumenib in the Journal of Clinical Oncology. The trial met its primary endpoint for patients with KMT2Ar AML and ALL. The FDA is reviewing the New Drug Application (NDA) for revumenib under Priority Review, with a PDUFA action date of December 26, 2024.

Key highlights:

• Revumenib showed impressive clinical profile in relapsed/refractory KMT2Ar acute leukemia
• NDA is being reviewed under FDA's Real-Time Oncology Review Program
• Potential for revumenib to be a paradigm-changing treatment
• Topline data for mNPM1 AML expected in Q4 2024, possibly supporting a supplemental NDA in H1 2025

Positive

• AUGMENT-101 trial met its primary endpoint for KMT2Ar AML and ALL patients (p-value = 0.0036)
• FDA granted Priority Review for revumenib's NDA with PDUFA date of December 26, 2024
• Revumenib showed high rate of deep, MRD negative responses in clinical trials
• Safety profile supports prolonged time on therapy and maintained remission post-stem cell transplant
• Potential for supplemental NDA filing for mNPM1 AML in first half of 2025

Negative

• None.

Oncology Researcher

The publication of the AUGMENT-101 trial results in the Journal of Clinical Oncology is a significant milestone for Syndax Pharmaceuticals. The trial's success, meeting its primary endpoint with a p-value of 0.0036, demonstrates the strong efficacy of revumenib in treating KMT2Ar acute leukemia. This is particularly noteworthy given the lack of effective therapies for this specific genetic subtype.

The high rate of deep, MRD negative responses is a critical factor in leukemia treatment, as it often correlates with improved long-term outcomes. Additionally, the safety profile supporting prolonged therapy and maintained remission post-stem cell transplant suggests revumenib could potentially become a standard of care for these patients.

Regulatory Affairs Specialist

The FDA's acceptance of Syndax's NDA for revumenib under Priority Review and the Real-Time Oncology Review (RTOR) program is a strong indicator of the drug's potential impact. The PDUFA date of December 26, 2024, sets a clear timeline for potential market entry. The RTOR program is designed to expedite the review process for promising cancer treatments, which speaks to the FDA's recognition of revumenib's potential significance.

Furthermore, the ongoing trial for mNPM1 AML patients could lead to a supplemental NDA in 2025, potentially expanding revumenib's market reach. This dual-pronged approach in targeting both KMT2Ar and mNPM1 mutations demonstrates a strategic pipeline development plan.

Market Analyst

Syndax Pharmaceuticals' progress with revumenib positions the company favorably in the competitive oncology market. The potential first-in-class status for a menin inhibitor in KMT2Ar acute leukemia could provide a significant market advantage. With a PDUFA date in December 2024, Syndax is poised for a potential revenue stream in the near future, assuming FDA approval.

Investors should note the company's proactive commercial launch preparations, which could facilitate rapid market penetration post-approval. The additional opportunity in mNPM1 AML further strengthens Syndax's market position. However, it's important to monitor the upcoming topline data from the mNPM1 cohort in Q4 2024, as it will impact the company's growth trajectory and potential market expansion.

– 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.

FAQ

What is the PDUFA date for Syndax's revumenib (SNDX) in KMT2Ar acute leukemia?

The PDUFA target action date for Syndax's revumenib (SNDX) in KMT2Ar acute leukemia is December 26, 2024.

What were the results of Syndax's AUGMENT-101 trial for revumenib (SNDX)?

The AUGMENT-101 trial met its primary endpoint for patients with KMT2Ar AML and ALL, with a p-value of 0.0036.

When does Syndax (SNDX) expect topline data for revumenib in mNPM1 AML?

Syndax (SNDX) expects topline data for revumenib in mNPM1 AML in the fourth quarter of 2024.

What type of review is the FDA conducting for Syndax's revumenib (SNDX) NDA?

The FDA is reviewing Syndax's revumenib (SNDX) NDA under Priority Review and the Real-Time Oncology Review Program (RTOR).