Revuforj (revumenib) in Acute Myeloid Leukemia (AML) - Syndax Pharmaceuticals
Revuforj is a Menin inhibitor that received FDA approval in November 2024 for relapsed/refractory (R/R) AML patients with a KMT2A translocation. Revuforj was approved on the basis of the Phase I/II AUGMENT-101 study. The complete response (CR) rate + CR with partial hematologic recovery was 21.2% (n=104) and the median duration of complete response was 6.4 months. Patients received a median of 2 prior lines of therapy.
Revuforj marks a very important advancement in AML, not only because it is the first Menin inhibitor approved in oncology, but also because it is a biomarker-driven agent that adds one more option in the limited treatment landscape of R/R AML, and potentially even extends the number of lines of therapy administered due to its differentiated mechanism of action (MOA). Jefferies analysts previously placed Revuforj's peak sales at $200M [1].
Blincyto (blinatumomab) in Acute Lymphocytic Leukemia (ALL) – Amgen
Blincyto is a CD19/CD3 bispecific monoclonal antibody (mAb) that received a label expansion by the FDA in June 2024 for the consolidation treatment of Philadelphia chromosome-negative B-ALL adult and pediatric patients in combination with chemotherapy. The approval was granted based on the NCI-funded Study E1910 Phase III study (n=224). The 3-year overall survival (OS) was 84.8% for Blincyto + chemotherapy vs 69% for chemotherapy only (HR: 0.42). This difference was sustained at 5 years with an HR of 0.44.
Despite Blincyto being around for a long time (first approval in the R/R setting in 2014), this is an extremely important approval for B-ALL patients because it offers a higher chance at a cure and as such was welcome as the new 1L standard of care (SOC). Blincyto’s label expansion benefited from the FDA’s Project Orbis, which allowed submission and concurrent review among other international regulatory authorities. [2]
Rytelo (imetelstat) in Myelodysplastic Syndromes (MDS) – Geron
Rytelo is a lipid-conjugated oligonucleotide that inhibits telomerase activity and received FDA approval in June 2024 for the treatment of adults with low- to intermediate-1 risk MDS with transfusion-dependent anemia requiring four or more red blood cell units over 8 weeks who are unresponsive to or ineligible for erythropoiesis-stimulating agents. Approval was granted based on the IMerge Phase II/III study (n=178). The rate of ≥24-week red blood cell transfusion independence was 28% vs 3.3% for placebo.
Rytelo is groundbreaking not only because it is a first-in-class telomerase inhibitor, but it is also the first oligonucleotide therapeutics to receive FDA approval in oncology. Goldman Sachs previously valued the peak sales of Rytelo at $1.2B [3].
By Sakis Paliouras, PhD
References
[1] https://www.yahoo.com/news/syndax-secures-fda-ok-kind-121200875.html
