Zavabresib Granted Orphan Drug Designation for Myelofibrosis

The FDA has granted the bromodomain and extra-terminal motif (BET) small molecule inhibitor, OPN-2853 (zavabresib), orphan drug designation for the treatment of myelofibrosis (MF), according to the manufacturer.¹ The FDA’s decision was based on data presented at the American Society of Hematology in December 2025, which demonstrated a 50% or greater reduction of spleen length in 16 of 26 evaluable patients on the combination treatment when compared to baseline in the PROMise study (EudraCT #2019-000916-27).²

Study Design

PROMise is a phase 1, multicenter, dose finding trial evaluating 3 dose levels of zavabresib: 20 mg, 40 mg, and 80 mg. A maximum of 40 patients with advanced myelofibrosis will be recruited across 2 ruxolitinib dose groups: low dose (5 to 20 mg daily) or a mid/high dose (> 25 mg daily).

The coprimary objectives of the study are to identify a safe and tolerable recommended phase 2 dose (RP2D) of zavabresib in combination with ruxolitinib and assessing the efficacy of the combination in reducing spleen size in patients who have not responded to ruxolitinib monotherapy.

Twenty-nine patients registered. Of those, 14 received 40 mg and 15 received 80 mg of zavabresib plus ruxolitinib (low dose = 8; mid/high dose = 21). At registration, patients were a median age of 70 years old (range, 65-74), the majority (52%) were male, and 76% were transfusion independent.

Results

Median time on treatment was 6.5 months, with 7 out of 29 patients on treatment for more than 1 year. Four of 29 patients were on treatment for more than 2 years. Median time on follow-up was 12 months, according to investigators.

Of the 14 patients with non-missing baseline and post-baseline MF grades, 4 (28.6%) patients had a best improvement of at least 1 grade. In 28 and 22 patients with evaluable palpation and ultrasound spleen data, the median palpation spleen size was reduced by 6 cm (range, 4.3-8.0). The ultrasound spleen length was reduced by 1 cm (range, 0.0-3.0).

Safety

The most common grade 3 or above adverse events (AEs) were decreased platelet count (n = 6; 20.7%) and anemia (n = 2; 6.9%). In total, platelet count decreased in 10 patients (34.5%). The most common non-hematologic AEs were diarrhea (n = 18; 62.1%) and nausea (n = 14; 48.3%). Bleeding related AEs were hemorrhage (20.7%), epistaxis (17.2%), and hematuria (3.4%). There were 2 reported disease related deaths. No patients experienced a serious AE that transformed to leukemia.

Overall, continuous dosing of OPN-2853 was well-tolerated, allowing prolonged treatment. Encouraging levels of spleen length reduction and a manageable assessment and molecular data, and no patients experienced leukemic progression safety profile have been observed with combination OPN-2853 and ruxolitinib treatment.

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 22, 2026. https://tinyurl.com/4yx32df4

2. 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. Presented at: 67th American Society of Hematology Annual Meeting and Exposition. December 6-9, 2025. Orlando, FL. Abstract-3794