FDA Grants Orphan Drug Status to Ofirnoflast for Patients with MDS

The FDA has granted orphan drug designation to the investigational drug ofirnoflast (HT-6184) for the treatment of myelodysplastic syndromes (MDS).

“This designation underscores the potential of our approach in myelodysplastic syndromes and supports our commitment to developing new treatment options for patients living with MDS,” David Bearss, PhD, CEO of Halia Therapeutics, the developer of ofirnoflast, said in a press release.¹ “Ofirnoflast represents a first-in-class approach to modulating inflammasome biology, an upstream driver of inflammation, with the goal of restoring healthy bone marrow function.”

Ofirnoflast is a selective NEK7 allosteric modulator designed to prevent the formation and promote the disassembly of the NLRP3 inflammasome.

“Inflammasome biology represents a promising frontier for hematologic innovation,” Alan F. List, MD, member of Halia Therapeutics’ Scientific Advisory Board and former president and CEO of Moffitt Cancer Center, said in a press release.¹ “Ofirnoflast’s approach is distinctive in that it seeks to modulate the underlying inflammatory drivers of MDS rather than just its downstream effects. This strategy has the potential to redefine how inflammation-linked bone marrow failure is treated.”

A phase 2a study (NCT07052006)² examined the effects of ofirnoflast in patients with very low, low, or intermediate risk MDS. There was a total enrollment of 37 patients. The study measured the rate of hematological improvement over 16 weeks.

Patient inclusion criteria included, but were not limited to, adequate organ function, a documented diagnosis of MDS, less than 10% bone marrow myeloblasts, and an ECOG score of 0 to 2.

Patient exclusion criteria included, but were not limited to, other causes of anemia, such as an iron deficiency, secondary MDS, clinically significant anemia resulting from B12 or folate deficiencies, and a prior history of malignancy other than MDS.

The agent has a history of favorable safety and tolerability in other clinical studies. For example, a phase 1 study (NCT05447546)³ previously examined the agent’s safety and tolerability in healthy volunteer subjects when administered orally.

In an additional phase 2 trial (NCT06241742),⁴ ofirnoflast produced a hematological improvement-erythroid response after 16 weeks of monotherapy. This exceeded the preset requirement of at least 3 responders.

Under the FDA’s Orphan Drug Act, this status provides several incentives, such as tax credits for qualified clinical testing, exemption from FDA user fees, and potential for 7 years of market exclusivity upon approval. This designation is granted to agents that fill serious unmet needs in diseases affecting fewer than 200,000 patients in the US.

REFERENCES:

1. Ofirnoflast (HT-6184) receives orphan drug designation from U.S. FDA for myelodysplastic syndromes. Press release. Halia Therapeutics. October 23, 2025. Accessed October 24, 2025. https://tinyurl.com/5czk6rkc

2. HT-6184 in subjects with MDS. ClinicalTrials.gov. Updated July 14, 2025. Accessed October 24, 2025. https://clinicaltrials.gov/study/NCT07052006

3. Study to evaluate HT-6184 in healthy subjects. ClinicalTrials.gov. Updated August 28, 2023. Accessed October 24, 2025. https://clinicaltrials.gov/study/NCT05447546

4. Evaluating ability of HT-6184 to reduce inflammation and pain after third molar extraction. ClinicalTrials.gov. Updated March 30, 2025. Accessed October 24, 2025. https://clinicaltrials.gov/study/NCT06241742