Ofirnoflast, a first-in-class allosteric NEK7 inhibitor, showed favorable safety and clinically significant efficacy in patients with low-risk myelodysplastic syndromes (LR-MDS) refractory to erythropoietin stimulating agents (ESA), according to a single-arm phase 2 trial presented at the Fourteenth Annual Meeting of the Society of Hematologic Oncology in Houston, Texas.
Treatment with ofirnoflast led to transfusion independence (TI) for eight or more weeks in 55% of transfusion–dependent patients, and 63% of evaluable patients had a hematologic improvement (HI) in erythroids (HI-E) with a maximum median hemoglobin increase of 4.6 g/dL, wrote the study’s authors, led by Varun Bafna, MD, of University of California, San Francisco.
The study enrolled 37 Asian patients (62% male) with a median age of 66 years (range, 31-86), of which 49% had a high-transfusion burden (HTB), 14% had a low-transfusion burden (LTB), and 38% were nontransfusion-dependent (NTD). In addition, 54% were refractory to ESAs, 22% were intolerant to ESAs, and 24% were ineligible for ESAs. The median duration of treatment was 32 weeks.
Overall, treatment-emergent adverse events (TEAEs) occurred in 51.4% of patients, most of which were grade 1 or 2. Grade 3 or higher TEAEs and serious adverse events occurred in 10.8% and 8.1% of patients, respectively. Among responders, 70% of patients maintained TI for 16 or more weeks, with a median TI duration of 28 weeks. In NTD patients, 75% achieved HI-E. Responses occurred across MDS subtypes and somatic gene mutation subgroups including SF3B1 and chromosome 5q deletion.
“These phase 2 results establish allosteric NEK7/NLRP3 inhibition as a potentially mechanistically novel and effective treatment strategy in LR-MDS,” the report concluded.
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