What is the likelihood of Revuminib (generic name) receiving FDA (Food and Drug Administration) approval?

Likelihood of Revumenib Receiving FDA Approval

Revumenib has already received FDA approval on November 15,2024, for the treatment of relapsed or refractory acute leukemia with a KMT2A translocation in adult and pediatric patients 1 year and older. 1

Approval Details and Clinical Evidence

• Revumenib is an oral, first-in-class menin inhibitor that blocks the interaction between menin and the KMT2A protein complex, promoting differentiation and exerting antileukemic activity 1
• The FDA approval was based on the phase 2 AUGMENT-101 clinical trial, which demonstrated significant efficacy in patients with KMT2A-rearranged acute leukemias 2, 3
• In the efficacy-evaluable population (n=57), revumenib achieved a complete remission (CR) or complete remission with partial hematologic recovery (CRh) rate of 22.8% (95% CI, 12.7 to 35.8), exceeding the null hypothesis of 10% (P=.0036) 3
• The overall response rate was 63.2% (95% CI, 49.3 to 75.6), with 15 of 22 patients (68.2%) having no detectable residual disease 3

Safety Profile

• Common grade 3/4 adverse reactions reported for revumenib include:
  • Febrile neutropenia (33-37.2%) 4, 3
  • Infections (29%) 4
  • Differentiation syndrome (13-16%) 4, 3
  • QT prolongation (12-13.8%), which was the primary dose-limiting adverse effect 4, 3
• Treatment-related adverse events led to treatment discontinuation in only 4.8% of patients in the NPM1-mutated cohort 5

Expanded Indications Under Investigation

• Beyond its current approval, revumenib is being evaluated for NPM1-mutated (NPM1m) acute myeloid leukemia (AML) in the same AUGMENT-101 trial 1, 5
• In the NPM1m AML cohort (n=64), revumenib demonstrated a CR+CRh rate of 23.4% (1-sided P=.0014) and an overall response rate of 46.9% 5
• The median duration of CR+CRh was 4.7 months, and 16.7% of responders proceeded to hematopoietic stem cell transplant 5

FDA Approval Process Insights

• The approval of revumenib follows a pattern seen with other targeted therapies for rare oncology indications, where the FDA has granted approvals based on single-arm trials showing significant efficacy in populations with high unmet needs 6
• For oncology drugs with supporting real-world evidence (RWE) for efficacy, the FDA has typically granted full approval when the following conditions are met: orphan disease designation, breakthrough therapy designation, priority review, and high level of primary efficacy in the pivotal trial (ORR >70%) 6
• The FDA has previously approved targeted therapies such as larotrectinib and entrectinib for gene fusion-positive solid tumors, establishing a precedent for the approval of targeted therapies based on genetic alterations rather than tumor type 7

Clinical Significance

• Revumenib represents a significant advancement in the treatment of KMT2A-rearranged acute leukemias, which previously had limited treatment options 4
• The drug serves as a viable treatment option that can potentially bridge patients to stem cell transplant 4
• The approval of revumenib marks the first targeted therapy specifically for KMT2A-rearranged acute leukemias 3