FDA Grants Priority Review to Syndax's Revuforj® (revumenib) for Relapsed/Refractory mNPM1 AML

Analysis reveals significant industry trends and economic implications

Release Date

2025-06-25

Category

Drug Approval Event

Reference

Source

Breakthrough Clinical Results

Syndax Pharmaceuticals announced that the FDA granted Priority Review to its supplemental New Drug Application (sNDA) for Revuforj® (revumenib) to treat relapsed or refractory (R/R) mutant NPM1 (mNPM1) acute myeloid leukemia (AML). The sNDA is under the FDA's Real-Time Oncology Review (RTOR) program, with a PDUFA date of October 25, 2025. Revuforj, a first-in-class oral menin inhibitor, is already approved for R/R acute leukemia with a KMT2A translocation. This approval would expand its use to the most common genetic alteration in AML. The sNDA is supported by positive data from the AUGMENT-101 trial, published in *Blood* and presented at the EHA Annual Congress.

Key Highlights

  • FDA granted Priority Review to Syndax's sNDA for Revuforj® (revumenib) in R/R mNPM1 AML.
  • PDUFA target action date is October 25, 2025.
  • Revuforj could become the first menin inhibitor approved for both R/R mNPM1 AML and R/R KMT2A-r AML.
  • The sNDA is supported by positive data from the AUGMENT-101 trial.

Incidence and Prevalence

Global Epidemiology of Acute Myeloid Leukemia

Global Incidence and Burden

Acute myeloid leukemia (AML) is one of the four main subtypes of leukemia studied globally. According to a comprehensive global study analyzing data from 1990 to 2019 across 204 countries and territories, the total number of incident cases of all leukemia types globally in 2019 was 0.64 million, with 0.33 million deaths and 11.66 million disability-adjusted life-years (DALYs).

While specific global AML-only figures aren't detailed in the context, we know that in the United States specifically, there are about 10,000 new cases of AML and 7,000 deaths in those with an AML diagnosis per year.

Regional Variations and Trends

Korea

  • AML was the most frequent subtype of myeloid malignancies in Korea
  • The age-standardized incidence rate (ASR) for AML in 2012 was 2.02 per 100,000 persons
  • The ASR for all myeloid malignancies increased from 3.31 in 1999 to 5.70 in 2012 with an annual percentage change (APC) of 5.4%
  • Five-year relative survival rate (RS) for AML in Korea changed from 26.3% to 34.8% between 1996-2000 and 2008-2012
  • Survival rates for acute promyelocytic leukemia (APL) improved from 51.6% to 69.6% and for non-APL AML from 23.8% to 29.9% between 1996-2000 and 2008-2012

Croatia

  • Acute myeloid leukemia incidence significantly increased in women, with an estimated annual percentage change (EAPC) of 2.6%
  • In men, AML incidence increased since 1998, with an EAPC of 3.2%

Bangladesh

  • Among adolescents and young adults (15-39 years), AML was the most frequent hematological malignancy (35.1%), followed by acute lymphoblastic leukemia (ALL) and chronic myeloid leukemia (CML)

California, USA

  • The overall incidence of acute myeloid leukemia remained stable but increased among Hispanics (APC, 1.2%), females (APC, 1.0%), Hispanic females (APC, 2.3%), and Hispanic females aged 15-19 years (APC, 3.4%)
  • The incidence of acute myeloid leukemia did not appear to differ among racial/ethnic groups

Mexico City

  • Acute myeloblastic leukemia constituted 12.3% of leukemia cases with a standardized average annual incidence rate (SAAIR) of 6.9 per million

United Arab Emirates

  • t(15;17) and t(8;21) were the most frequent chromosomal abnormalities in AML patients, observed in 13.2% and 12.4% of patients, respectively
  • Unusual or novel cytogenetic abnormalities were found in 17% of AML patients, suggesting geographic heterogeneity in the pathogenesis of AML

Demographic Patterns

  • The highest incidence of myeloid malignancies was observed in the age 70s with male predominance (1.3:1)
  • AML, along with chronic myeloid leukemia (CML) and chronic lymphocytic leukemia (CLL), imposes a greater burden on the elderly population
  • The incidence of AML increases with age, peaking in the sixth decade of life
  • The leukemia burden was heavier in males than in females

Global Trends and Projections

  • Decreasing trends in age-standardized incidence rate (ASIR), age-standardized death rate (ASDR), and age-standardized DALY rate were detected on a global level
  • However, increasing trends in ASIR were detected in high-sociodemographic index (SDI) regions
  • Future projections through 2030 estimated that ASIR and ASDR will continue to increase, while the DALY rate is predicted to decline
  • Smoking remained the most significant risk factor associated with leukemia-related death and DALY, especially in males

Key Unmet Needs in Acute Myeloid Leukemia

Therapeutic Challenges

Despite advances in cancer treatment, Acute Myeloid Leukemia (AML) faces significant unmet needs, particularly in immune therapy development. Unlike other cancers with successful immune therapies, AML presents unique challenges:

  • The lack of AML-specific target antigens remains a major obstacle
  • Current approaches targeting non-specific antigens (CD33, CD123, CLL-1) cause unacceptable bone marrow toxicity and off-target adverse events
  • Studies of antibodies targeting these antigens show unconvincing efficacy alongside substantial adverse events
  • AML's low mutation frequency compared to solid cancers results in few neo-antigens, creating special problems for immune therapy development
  • Evidence suggests limited immune surveillance against AML

Despite promising pre-clinical studies of antibodies that disinhibit T cells and macrophages by blocking checkpoint receptors, there are currently no immune-based therapies for AML on the market except for gemtuzumab ozogamicin.

Demographic and Socioeconomic Disparities

Significant disparities exist in AML clinical trials and treatment access:

  • Under-representation of Blacks, Native Americans, and Hispanics in pivotal clinical trials
  • Gender imbalance with females being under-represented (44.7% vs 60.5%)
  • Geographic disparities showing inadequate regional and state participation compared with mortality

Socioeconomic factors significantly affect treatment access: - Patients with lower socio-economic position more often do not receive cancer-directed treatment - Approximately 26% of AML patients do not receive cancer-directed treatment, primarily due to physical condition or rapid disease progression

Promising Approaches Under Investigation

Several innovative approaches are being investigated to address these unmet needs:

  • Cellular therapies: CAR-T, CAR-NK, adaptor CAR-T, and allogeneic NK-cells

  • Antibody therapies:

  • Anti-CD47 monoclonal antibodies showing efficacy when combined with azacitidine

  • Bispecific antibodies (anti-CD3/CD123, anti-CD33)

  • Immune checkpoint inhibitors: PD-1 inhibitors for patients with peripheral circulating CD4+ PD1+ and CD8+ PD1+ T lymphocytes

  • Combination approaches:

  • Selective targeted epigenetic drugs with cellular immunotherapy

  • Curcumin combined with arsenic trioxide showing potential to enhance NK cell immunosurveillance

These emerging approaches aim to overcome the significant challenges in developing effective immune therapies for AML while addressing the demographic and socioeconomic disparities that currently limit optimal treatment for all patients.

Drug used in other indications

Revuforj (Revumenib) Clinical Trials Beyond AML

Based on the provided information, there is no specific information about Revuforj (revumenib) being investigated for oncological or hematological malignancies beyond acute myeloid leukemia (AML) in clinical trials.

The available information only mentions that Revumenib demonstrated efficacy in "KMT2A-rearranged and NPM1-mutated leukemias" without specifying other cancer types beyond AML.

Revumenib received FDA approval in November 2024 after demonstrating "consistent efficacy across five pivotal trials, achieving MRD-negative rates of 70-90% in both KMT2A-rearranged and NPM1-mutated leukemias."

While the information indicates that Menin inhibitors (the class of drugs to which revumenib belongs) are being investigated in "acute leukemias with KMT2A rearrangements or NPM1 mutations," it does not specify non-AML indications for revumenib specifically.