Syndax Pharmaceuticals is poised for a transformative period, marked by anticipated milestones for its key drug candidates, revumenib and Niktimvo. The company's strategic focus on innovative cancer therapies is underscored by upcoming clinical data presentations and a pending FDA decision that could significantly impact treatment paradigms for acute leukemia.
Revumenib: Approaching Potential Approval and Data Milestones
The New Drug Application (NDA) for revumenib, an oral menin inhibitor, is under Priority Review by the FDA for the treatment of relapsed or refractory (R/R) KMT2A-rearranged (KMT2Ar) acute leukemia. A Prescription Drug User Fee Act (PDUFA) target action date is set for December 26, 2024, signaling a potentially imminent approval.
Furthermore, Syndax expects to report topline data from the AUGMENT-101 pivotal trial cohort, evaluating revumenib in patients with R/R mutant nucleophosmin (mNPM1) acute myeloid leukemia (AML), in the fourth quarter of 2024. Positive results from this trial could pave the way for a supplemental NDA (sNDA) filing for revumenib in R/R mNPM1 AML in the first half of 2025.
Data from the pivotal Phase 2 portion of the AUGMENT-101 trial of revumenib in adult and pediatric patients with R/R KMT2Ar AML and acute lymphoid leukemia (ALL) have been published in the Journal of Clinical Oncology. A larger data set with longer follow-up will be presented at the upcoming 66th American Society of Hematology (ASH) Annual Meeting. This updated analysis includes a larger efficacy population (n=97) and demonstrates durable responses, robust rates of overall response, minimal residual disease (MRD) negativity, and hematopoietic stem cell transplantation (HSTC).
Several ongoing trials are evaluating the potential to expand revumenib use across the mNPM1 and KMT2Ar acute leukemia treatment landscape. These include:
- BEAT AML: A Phase 1 trial evaluating the combination of revumenib with venetoclax and azacitidine in front-line AML patients. Updated positive data from the trial at the European Hematology Association (EHA) 2024 Congress, showed a 96% (23 of 24 pts) composite complete remission (CRc) rate in patients with newly diagnosed mNPM1 or KMT2Ar AML.
- SAVE: A Phase 1 trial evaluating the all-oral combination of revumenib with venetoclax and decitabine/cedazuridine in R/R AML or mixed phenotype acute leukemias. Updated data showing an 88% ORR (23 of 26 pts) in R/R patients with KMT2Ar, mNPM1, or NUP98r leukemias will be presented at the upcoming 66th ASH Annual Meeting.
- INTERCEPT: A Phase 1 trial evaluating the use of novel therapies, including revumenib, to target MRD and early relapse in AML. Preliminary results from the first eight mNPM1 patients treated with revumenib will be presented at the upcoming 66th ASH Annual Meeting.
Syndax plans to initiate a pivotal trial of revumenib in combination with venetoclax and azacitidine in newly diagnosed mNPM1 or KMT2Ar acute leukemia patients unfit to receive intensive chemotherapy by year-end 2024.
Niktimvo™ (axatilimab-csfr): Commercial Launch and Clinical Expansion
Niktimvo (axatilimab-csfr) received FDA approval for the treatment of chronic graft-versus-host disease (GVHD) after failure of at least two prior lines of systemic therapy in adult and pediatric patients weighing at least 40 kg (88.2 lbs). The company anticipates launching Niktimvo in the U.S. no later than early first quarter 2025. In the U.S., Niktimvo will be co-commercialized by Syndax and Incyte.
Niktimvo was added to the latest NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) as a category 2A recommendation for the treatment of GVHD after the failure of at least two prior lines of systemic therapy in adult and pediatric patients weighing at least 40 kg.
Results from the pivotal Phase 2 AGAVE-201 trial of Niktimvo in adult and pediatric patients with recurrent/refractory active chronic GVHD who had received at least two prior lines of systemic therapy were published in the New England Journal of Medicine.
A secondary analysis of overall and organ-specific responses from the pivotal Phase 2 AGAVE-201 trial of Niktimvo in adult and pediatric patients with recurrent/refractory active chronic GVHD who had received at least two prior lines of systemic therapy will be presented at the 66th ASH Annual Meeting. The data demonstrated rapid responses and symptom improvement in inflammatory and fibrotic manifestations of chronic GVHD in heavily pretreated patients.
Enrollment is ongoing in the MAXPIRe trial, a 26-week randomized, double-blinded, placebo-controlled Phase 2 trial of axatilimab on top of standard of care in patients with idiopathic pulmonary fibrosis (IPF) (NCT06132256). Topline data from the trial are expected in 2026.
Incyte is recruiting patients for a Phase 2 trial of axatilimab in combination with ruxolitinib in patients ≥12 years of age with newly diagnosed chronic GVHD (NCT06388564). A Phase 3 trial of axatilimab in combination with steroids for the treatment of chronic GVHD is currently in preparation.
Financial Position and Future Outlook
Syndax secured a $350 million royalty funding agreement with Royalty Pharma based on U.S. net sales of Niktimvo. This agreement provides Syndax with substantial financial resources to support its ongoing clinical programs and commercialization efforts. The company expects to be funded through profitability, driven by anticipated product revenue and strategic financial management.
As of September 30, 2024, Syndax had cash, cash equivalents, and short- and long-term investments of $399.6 million. For the full year of 2024, the Company expects research and development expenses to be $245 to $250 million and total operating expenses to be $365 to $370 million.
