Syndax Presents Updated Positive Data from BEAT AML and AUGMENT-102 Phase 1/2 Combination Trials of Revumenib in Patients with Acute Leukemias at EHA 2024 Congress
Syndax Pharmaceuticals announced updated positive data from two combination trials of revumenib in patients with acute leukemias at the EHA 2024 Congress.
In the BEAT AML trial, a 96% composite complete remission (CRc) rate was observed in newly diagnosed AML patients treated with revumenib in combination with venetoclax and azacitidine. The AUGMENT-102 trial showed a 52% CRc rate in relapsed/refractory acute leukemia patients treated with revumenib and fludarabine-cytarabine.
Both trials demonstrated strong efficacy and an acceptable safety profile. No new safety signals were observed, and most adverse events were manageable. These results support revumenib's potential as a promising treatment in various settings of acute leukemia, and further trials are planned.
- 96% CRc rate in BEAT AML trial.
- 52% CRc rate in AUGMENT-102 trial.
- High rate of MRD-negative responses (92% in BEAT AML).
- No new or increased safety signals observed.
- Strong efficacy in both newly diagnosed and relapsed/refractory settings.
- Most adverse events were manageable and resolved without complications.
- Support for revumenib as a potential front-line treatment.
- High incidence of adverse events: 46% of patients in BEAT AML experienced QTc prolongation.
- Grade 3 and above adverse events in over 40% of patients in AUGMENT-102.
- One DLT at the 163 mg q12h dose in AUGMENT-102.
- One patient death due to sepsis in AUGMENT-102, although not related to revumenib.
Insights
The data from Syndax Pharmaceuticals' trials highlight significant strides for revumenib in treating acute leukemias. The BEAT AML trial showed a remarkable 96% CRc rate among patients with newly diagnosed AML, suggesting that revumenib, when combined with venetoclax and azacitidine, may offer a potent new therapy option. This high response rate is coupled with an impressive 92% achieving minimal residual disease negative status, indicating that the treatment effectively targets leukemic cells down to very low levels.
Importantly, the safety profile reported aligns with existing treatments, showing no new or increased safety signals. This factor is important as it emphasizes revumenib's potential to integrate smoothly into current therapeutic regimens without added risk.
Additionally, the AUGMENT-102 trial's 52% CRc rate in a heavily pretreated pediatric population is encouraging. Notably, the tolerability in this group, despite prior treatments, suggests revumenib could be a viable option for relapsed/refractory cases where current treatments often fail.
In the context of acute leukemia treatment, achieving high CRc rates with manageable safety profiles can significantly impact patient outcomes and survival rates. Investors should watch for further trial developments and potential FDA approval, which could establish revumenib as a front-line therapy.
From a financial perspective, these trial results hold substantial potential for Syndax Pharmaceuticals. The impressive efficacy data from the BEAT AML and AUGMENT-102 trials positions revumenib as a strong candidate for FDA approval, which could drive significant revenue growth. The high CRc rates and safety profile suggest it could become a preferred treatment option, expanding the market reach.
Furthermore, the upcoming pivotal trial and potential near-term approval in the relapsed/refractory setting could lead to substantial short-term gains. Long-term, if revumenib integrates into standard care practices, it could secure a steady revenue stream for years.
However, investors should be aware of potential risks, including regulatory hurdles and competition from other emerging therapies. Keeping an eye on the pivotal trial's progress and any regulatory feedback will be critical in assessing Syndax's market position.
These trials underscore a strategic positioning for Syndax in the acute leukemia treatment landscape. The high CRc rates in both newly diagnosed and relapsed/refractory patient groups demonstrate revumenib's broad applicability and potential market penetration.
Syndax's focus on combination therapies, pairing revumenib with existing standards like venetoclax/azacitidine, aligns with current oncological trends emphasizing multi-drug regimens to enhance efficacy. This approach not only leverages the strengths of revumenib but also facilitates easier adoption by clinicians familiar with these existing treatments.
Moreover, the pediatric population results show promise for expanding revumenib's use across different age groups, potentially boosting its market appeal. The strategic pipeline development and robust trial outcomes make Syndax a company to watch in the competitive oncology market.
- Data continue to support revumenib's potential to enhance current standard of care agents -
-
-
"The growing body of data supports the potential for revumenib to have a meaningful impact in combination with current standard of care therapies," said Joshua F. Zeidner, M.D., Chief, Leukemia Research at the University of North Carolina, Lineberger Comprehensive Cancer Center. "Based on the BEAT AML data in the newly diagnosed setting which showed a high rate of MRD-negative responses coupled with a safety profile that enables combination use, revumenib has the potential to become a cornerstone of treatment as front-line therapy for newly diagnosed KMT2Ar and mNPM1 AML."
"We are committed to advancing revumenib across a spectrum of acute leukemia patients. As we prepare for the expected near-term approval of revumenib in the relapsed or refractory setting, we look forward to providing additional clinical data as monotherapy and in combination to support treatment in various acute leukemia treatment settings where novel treatment options are urgently needed," said Neil Gallagher, M.D., Ph.D., President, Head of Research and Development at Syndax.
BEAT AML Trial
The Company announced updated data from the BEAT AML trial of revumenib in combination with venetoclax/azacitidine in newly diagnosed mutant nucleophosmin (mNPM1) or KMT2A-rearranged (KMT2Ar) acute myeloid leukemia (AML) patients aged 60 years or older in an oral presentation titled "Phase 1b Study of Azacitidine, Venetoclax and Revumenib in Newly Diagnosed Older Adults with NPM1 Mutated or KMT2A Rearranged AML: Interim Results of Dose Escalation from the BeatAML Consortium."
The dose escalation phase of the trial tested revumenib at doses of 113 mg and 163 mg q12h in combination with a strong CYP3A4 inhibitor beginning on day 1 of a 28-day cycle in combination with on label doses of venetoclax and azacitidine. As of the data cutoff date of May 1, 2024, 26 newly diagnosed mNPM1 (n=17) or KMT2Ar (n=9) AML patients were enrolled. In the efficacy evaluable population, the composite complete remission1 (CRc) rate was
Revumenib was dosed safely at both the 113 mg and 163 mg q12h dose in combination with venetoclax and azacitidine.
An expansion cohort is ongoing at both dose levels to establish the recommended dose for future trials. The Company plans to initiate a pivotal trial with this combination in front-line newly diagnosed patients by year-end 2024.
AUGMENT-102 Trial
The Company also announced a poster presentation featuring updated data from the AUGMENT-102 trial of revumenib in combination with fludarabine/cytarabine in a predominantly pediatric population of patients with relapsed/refractory (R/R) mNPM1 (n=2), NUP98-rearranged (NUP98r) (n=1) or KMT2Ar (n=23) AML titled "Safety and Activity of Revumenib in Combination with Fludarabine/Cytarabine (FLA) in Patients with Relapsed/Refractory Acute Leukemias."
As of the data cutoff date of January 15, 2024, 27 patients received revumenib plus FLA, including 9 patients treated at 113 mg q12h and 18 treated at 163 mg q12h. The patients enrolled had a median age of 6 years and had received a median of 3 prior lines of therapy. Eighteen (
Overall, revumenib was tolerable in heavily pretreated patients with KMT2Ar, NUP98r, or NPM1m acute leukemias without increased frequency or severity of AEs compared with historic FLA data or revumenib monotherapy. One DLT occurred at the 163 mg q12h dose that was a Grade 4 decreased neutrophil count in a patient with multiple prior transplants.
Grade 3 and above adverse events in over
This study supports the selection of revumenib 163 mg q12h (95 mg/m2 q12h if weight <40 kg) combined with FLA and a strong cytochrome P450 inhibitor as the RP2D, in line with the dose of revumenib under FDA review as a monotherapy agent.
Additional Presentations at EHA 2024
In addition to updated results from the BEAT AML and AUGMENT-102 studies, an encore presentation of results from the pivotal AUGMENT-101 study of revumenib in R/R KMT2Ar acute leukemia were also featured at the Congress during an oral session titled "Revumenib Monotherapy in Patients with Relapsed/Refractory KMT2Ar Acute Leukemia: Topline Efficacy and Safety Results from the Pivotal AUGMENT-101 Phase 2 Study."
Results from an exploratory analysis of immunophenotypic changes in AML blasts following treatment with revumenib were also featured in a poster presentation titled "Characterization of Immunophenotypic Changes Following Menin Inhibition in Acute Myeloid Leukemia."
Copies of EHA posters and presentations will be available in the Publications and Meeting Presentations section of Syndax's website.
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 data from the Phase 1 portion of AUGMENT-101 in acute leukemia was published in Nature. Revumenib was granted Orphan Drug Designation by the FDA and European Commission for the treatment of patients with AML 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 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
1Composite 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
Syndax Contact
Sharon Klahre
Syndax Pharmaceuticals, Inc.
sklahre@syndax.com
Tel 781.684.9827
SNDX-G
View original content:SOURCE Syndax Pharmaceuticals, Inc.
FAQ
What is the CRc rate observed in the BEAT AML trial of revumenib?
What combination was used in the AUGMENT-102 trial with revumenib?
What was the patient response rate in the AUGMENT-102 trial?
Did the BEAT AML trial report any new safety signals with revumenib?
What was the age of patients in the AUGMENT-102 trial?
Did the trials report any Grade 3 or higher adverse events?
What is the significance of the MRD-negative response rate in the BEAT AML trial?
