Key takeaways
- The FDA has granted orphan drug designation to zavabresib for myelofibrosis based on data from the phase I PROMise study
- Spleen size reductions of ≥50% were observed in 16 of 26 patients on the receiving zavabresib plus ruxolitinib
- The combination therapy showed manageable safety findings, with common adverse events including decreased platelet count, anaemia and no leukaemic transformations reported.
- These results support further clinical development, particularly for patients with limited options after ruxolitinib progression.
The US Food and Drug Administration has granted orphan drug designation to zavabresib for the treatment of myelofibrosis. This regulatory milestone reflects encouraging early data from the phase I PROMise study, evaluating zavabresib in combination with the JAK inhibitor ruxolitinib.
Zavabresib is a bromodomain and extra-terminal (BET) inhibitor designed to bind the bromodomain (BRD) regions of BET proteins, resulting in downregulation of oncogenic transcriptional programs, including MYC, as well as BET inhibitor–responsive genes such as HEXIM1 and WDR47.
The PROMise trial, led by Professor Adam Mead at the University of Oxford in collaboration with Cancer Research UK, is a phase I, multicentre, dose-finding study enrolling patients aged 16 years or older with intermediate-2 or high-risk myelofibrosis who had an inadequate response to ruxolitinib monotherapy. Eligibility required prior treatment with ruxolitinib for at least 24 weeks, including a stable dose for a minimum of four weeks, as well as persistent splenomegaly measuring at least 5 cm below the costal margin.
Data presented at the 67th American Society of Hematology (ASH) Annual Meeting and Exposition showed that in patients with advanced myelofibrosis who had limited benefit from ruxolitinib alone, the zavabresib-ruxolitinib combination was associated with clinically meaningful reductions in palpable spleen size. In an evaluable cohort, roughly 50% or more experienced a ≥50% reduction in spleen length from baseline, suggesting durable organ response in a challenging patient population. Additional analyses pointed to median spleen size reductions of around 5–6 cm from baseline in subsets of patients.
Across the study, the combination was generally well-tolerated, with common adverse events including thrombocytopenia (low platelet counts) and anaemia, as well as gastrointestinal symptoms like diarrhea and nausea. Serious transformations to acute leukaemia were not observed in the data reported to date.
Myelofibrosis remains a condition with substantial unmet need, especially for patients who progress on or are intolerant to existing JAK inhibitors. The orphan designation for zavabresib highlights both the urgent need for new options and the potential of BET inhibition merged with JAK pathway targeting as a therapeutic strategy.
References
- Opna Bio. Opna Bio Announces Orphan Drug Designation Granted to OPN-2853 (Zavabresib) for the Treatment of Myelofibrosis. Available at: https://www.opnabio.com/opna-bio-announces-orphan-drug-designation-granted-to-opn-2853-zavabresib-for-the-treatment-of-myelofibrosis (Date last accessed: 27 January 2026)
- Mead AJ, Huntly BJP, Psaila B, et al. Interim analysis of PROMise, a clinical study combining the BET inhibitor OPN-2853 with ruxolitinib in patients with advanced myelofibrosis experiencing an inadequate response to ruxolitinib. Blood. 2024;144(suppl 1):3186
- Targeted Oncology. Zavabresib Granted Orphan Drug Designation for Myelofibrosis. Available at: https://www.targetedonc.com/view/zavabresib-granted-orphan-drug-designation-for-myelofibrosis (Date last accessed: 27 January 2026)
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This content has been developed independently by Touch Medical Media for touchHAEMATOLOGY. Views expressed are the speaker’s own and do not necessarily reflect the views of Touch Medical Media.
Cite: FDA grants orphan drug status to zavabresib in myelofibrosis. touchHAEMATOLOGY. 27th January 2026.
Editor: Sophie Nickelson, Editorial Director
Disclosures: This short article was prepared by touchHAEMATOLOGY. The content was developed and edited by human editors. No fees or funding were associated with its publication. touchHAEMATOLOGY utilize AI as an editorial tool (ChatGPT (GPT-4o) [Large language model]. https://chat.openai.com/chat).
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