FDA Grants Fast Track Designation to Ofirnoflast for Lower-Risk MDS

The FDA has granted fast track designation to ofirnoflast (HT-6184) for the treatment of adults with lower-risk myelodysplastic syndromes (LR-MDS). The designation follows phase 2 results presented at the European Hematology Association 2026 Congress showing durable transfusion independence and multilineage hematologic improvement.¹

Ofirnoflast is a first-in-class oral allosteric modulator of NEK7 that previously received FDA orphan drug designation. In the phase 2 study, ofirnoflast produced an overall best on-study hematologic improvement (HI) rate of 67% among 30 evaluable patients, with multilineage activity across erythroid (HI-E, 63%), platelet (HI-P, 60%), and neutrophil (HI-N, 60%) lineages.

Among 18 transfusion-dependent patients enrolled, 10 (56%) achieved red blood cell transfusion independence for at least 8 weeks, with a median duration of transfusion independence of 28 weeks; 39% of those responders maintained independence for 16 weeks or longer. Among the 12 patients who were not transfusion-dependent at baseline, 9 (75%) achieved HI-E. The median peak hemoglobin rise among responders was 4.6 g/dL (range, 0.8-7.4).

Activity was observed regardless of mutation profile and across WHO MDS subtypes, including patients with and without SF3B1 mutations or del(5q).

"Lower-risk MDS remains an area of substantial unmet need, particularly for patients who have exhausted available therapies," Han Myint, MD, chief medical officer of Halia Therapeutics, stated in a press release.¹ "The phase 2 data support further development of ofirnoflast as a potential new oral treatment option, and the FDA's fast track designation underscores both the need for innovation in this setting and the potential of our approach. We look forward to continuing our engagement with the agency as we prepare for the next stage of development."

Safety of Ofirnoflast

Ofirnoflast was generally well tolerated. No treatment-related serious adverse events were observed. Overall, treatment-related adverse events were mostly grade 1/2 and occurred in 27% of patients. Grade 3 or higher treatment-related adverse events were uncommon, occurring in 5.4% of patients.

Study Design and Patient Characteristics

The open-label, single-arm phase 2 trial enrolled 37 adults with LR-MDS defined by a revised International Prognostic Scoring System (IPSS-R) score of 4.5 or below who had symptomatic anemia or red blood cell transfusion dependence. All patients were refractory to, intolerant of, or ineligible for erythropoiesis-stimulating agents ESAs, which is a population with limited remaining treatment options following the failure of standard frontline therapy.

Patients received ofirnoflast 2 mg orally once daily on a 5-days-on/2-days-off schedule for up to 32 weeks.1 The primary end point was hematologic improvement per International Working Group 2018 criteria.

"Receiving fast track designation is an important milestone for Halia and reflects the significant unmet need that remains for patients with lower-risk MDS," David J. Bearss, PhD, chief executive officer of Halia Therapeutics, stated in the news release.¹ "The designation follows encouraging phase 2 results demonstrating durable transfusion independence and multilineage hematologic improvement and provides an important opportunity to work closely with the FDA as we advance ofirnoflast toward pivotal development. Patients who no longer respond to erythropoiesis-stimulating agents or erythroid maturation agents often face limited options and a substantial burden from chronic anemia and transfusion dependence."

Reference

1. Halia Therapeutics receives FDA Fast Track designation for ofirnoflast (HT-6184) in lower-risk myelodysplastic syndromes. News release. Halia Therapeutics. June 15, 2026. Accessed June 17, 2026. https://www.biospace.com/press-releases/halia-therapeutics-receives-fda-fast-track-designation-for-ofirnoflast-ht-6184-in-lower-risk-myelodysplastic-syndromes