Clinical Summary:

• Design/Population: This open-label, single-arm, phase 2 trial evaluated ofirnoflast in adult patients with very low-to intermediate-risk myelodysplastic syndromes with symptomatic anemia or red blood cell transfusion dependence who were refractory, intolerant, or ineligible for erythropoiesis-stimulating agents. 
• Key Outcomes: Ofirnoflast achieved hematologic improvement–erythroid responses in nearly two-thirds of efficacy-evaluable patients, with more than half of transfusion-dependent patients achieving red blood cell transfusion independence. Responses were durable and were also observed among non-transfusion dependent patients. 
• Clinical Relevance: These findings provide early clinical evidence that targeting NEK7/NLRP3 inflammasome signaling may restore effective erythropoiesis in lower-risk myelodysplastic syndromes, supporting ofirnoflast as a mechanistically novel treatment approach for patients with limited options following or in place of erythropoiesis-stimulating agent therapy.

Results from a phase 2 trial demonstrated that ofirnoflast produced clinically meaningful erythroid responses and durable red blood cell transfusion independence in patients with lower-risk myelodysplastic syndromes who were refractory, intolerant, or ineligible for erythropoiesis-stimulating agent therapy.

These results were presented by Varun Bafna, MD, Star Superspecialty Clinic and Hospital, Kolhapur, India, at the at the Society of Hematologic Oncology (SOHO) Annual Meeting in Houston, Texas. 

In this open-label, single-arm trial, 37 adult patients with Revised International Prognostic Scoring System very low-to intermediate-risk myelodysplastic syndromes and symptomatic anemia, defined as hemoglobin below 9 g/dL, or red blood cell transfusion dependence received 2 mg of once daily ofirnoflast on a 5-days-on, 2-days-off schedule for up to 32 weeks. The primary end point was hematologic improvement according to International Working Group 2018 criteria.

Among enrolled patients, 49% had a high transfusion burden, 14% had a low transfusion burden, and 38% were non-transfusion dependent. Overall, 54% were erythropoiesis-stimulating agent-refractory, 22% were erythropoiesis-stimulating agent-intolerant, and 24% were erythropoiesis-stimulating agent-ineligible.

Among 30 efficacy-evaluable patients, 63% of patients achieved hematologic improvement-erythroid. Of the  18 transfusion-dependent patients, 55% achieved red blood cell transfusion independence lasting at least 8 weeks. Among those who achieved transfusion independence, 70% maintained their response for at least 16 weeks, with a median duration of 28 weeks.

Responses were also observed among patients who were non-transfusion dependent, with 75% achieving hematologic improvement-erythroid. Among all hematologic improvement-erythroid responders, the median hemoglobin increase was 4.6 g/dL. Responses occurred across World Health Organization myelodysplastic syndrome subtypes and somatic mutation classes, including patients with SF3B1 alterations and del(5q). 

Ofirnoflast was generally well tolerated. Treatment-emergent adverse events occurred in 51.4% of patients and were predominantly grade 1/2. Grade ≥3 or treatment-emergent adverse events occurred in 10.8% of patients, and serious adverse events were reported in 8.1% of patients. 

As Dr Bafna concluded, “these phase 2 results establish allosteric NEK7/NLRP3 inhibition as a potential mechanistically novel and effective treatment strategy.”  

Source:

Bafna V, Nath U, Shah S, et al. Ofirnoflast (HT-6184), a first-in-class allosteric NEK7 inhibitor, achieves durable transfusion independence and hematologic improvement–erythroid in ESA-refractory lower-risk myelodysplastic syndrome: Phase 2 final results. Presented at the SOHO Annual Meeting; September 9-12, 2026; Houston, Texas. Abstract MDS-812.