Zavabresib Earns FDA Orphan Drug Designation in Myelofibrosis

The FDA has granted orphan drug designation to the investigational BET small molecule inhibitor zavabresib (OPN-2853) as a treatment for those with myelofibrosis, according to a press release from the developer, Opna Bio.¹

According to the developers, JAK inhibition represents the standard of care for patients with myelofibrosis, which helps limit cytokine production while mitigating symptoms like spleen volume.² Many patients, however, become refractory to JAK inhibitors. By selectively inhibiting the BET protein recognition of acetylated histones and downregulating oncogenic gene expression, zavabresib may be combined with other targeted drugs for full pathway inhibition. Specifically, zavabresib in combination with JAK inhibitors like ruxolitinib (Jakafi) may synergistically reduce inflammation, splenomegaly, and bone marrow fibrosis.

Evaluation of zavabresib plus ruxolitinib is ongoing among patients with myelofibrosis who no longer respond to ruxolitinib as part of the phase 1 PROMise study (2019-000916-27). Investigators shared data from the PROMise study at the 2025 American Society of Hematology Annual Meeting & Exposition (ASH).^3,4

Among 26 evaluable patients, data revealed that 16 achieved a 50% or higher reduction in their palpable spleen length compared with baseline. Additionally, the experimental regimen was well tolerated, and most patients completed 8 cycles of therapy.

“The emerging data from the PROMise study continue to be encouraging. We are now seeing consistent and clinically meaningful spleen size reductions, improvements in symptom burden, and durable benefit for patients who previously had limited options after an inadequate response to ruxolitinib alone,” Adam Mead, PhD, FRCP, FRCPath, FMedSci, a consultant physician and professor of Hematology from the Radcliffe Department of Medicine at the University of Oxford, stated in a press release regarding these findings.⁴ “These findings strengthen our view that selective BET inhibition alongside JAK inhibition may offer a new therapeutic approach for patients with myelofibrosis.”

Investigators of the phase 1 PROMise trial assessed whether zavabresib could be safely combined with ruxolitinib while restoring or increasing disease control among patients with myelofibrosis who previously experienced an inadequate response to ruxolitinib monotherapy. Patients were assigned to receive zavabresib at 40 mg (n = 14) or 80 mg (n = 15).

The trial’s primary end points were dose-limiting toxicities and a reduction of more than 50% for the palpable spleen from the time of screening to the end of cycle 8. Secondary end points included adverse effects (AEs), symptoms, and molecular responses.

Patients 16 years and older with primary or secondary Dynamic International Prognostic Scoring System Int-2 or High myelofibrosis were eligible for enrollment on the trial.

Data presented at ASH showed a median baseline spleen length of 20.2 cm (IQR, 16.3-23.0) per ultrasound, while the median length based on palpation was 9 cm (IQR, 6-15.3). Investigators observed 2 dose-limiting toxicities in the form of thrombocytopenia and elevated alanine aminotransferase, both of which occurred among patients who received 40 mg of zavabresib. Additionally, grade 3 or higher AEs included decreased platelet counts (25.0%) and anemia (8.3%). Among 9 evaluable patients, the mean change from baseline to cycle 8 in Brief Fatigue Inventory score was 0.9 (95% CI, 0-1.77).

“Receiving orphan drug designation for zavabresib in myelofibrosis is a significant regulatory milestone for Opna Bio and highlights the urgent need for new and effective treatment options for patients with this disease. Our investigator-sponsored clinical trial with zavabresib and ruxolitinib has shown impressive results to date, including durable spleen reduction in patients with advanced myelofibrosis,” Reinaldo Diaz, chief executive officer at Opna Bio stated regarding the orphan drug designation.¹ “We believe that selective BET inhibition alongside JAK inhibition offers a promising new therapeutic approach for patients with myelofibrosis. We are further encouraged by recent positive meetings with the FDA to continue to test zavabresib in additional clinical studies.”

References

1. Opna Bio announces orphan drug designation granted to OPN-2853 (Zavabresib) for the treatment of myelofibrosis. News release. Opna Bio. January 21, 2026. Accessed January 21, 2026. https://tinyurl.com/3nzfrw5t
2. Zavabresib (OPN-2853): potential best-in-class BET inhibitor. Opna Bio. Accessed January 21, 2026. https://tinyurl.com/saty4k74
3. Mead A, Psaila B, Boucher R, 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. 2025;146(suppl 1):3794. doi:10.1182/blood-2025-3794
4. Opna Bio showcases multi-functional degraders with potent anti-myeloma activity and encouraging spleen reductions in patients with myelofibrosis treated with OPN-2853 and ruxolitinib. News release. Opna Bio. December 8, 2025. Accessed January 21, 2026. https://tinyurl.com/3pxeap8f