Efficacy and safety of OB756 (a novel selective JAK2 inhibitor) for essential thrombocythemia in patients intolerant of or resistant to hydroxyurea or intolerant of interferon: A phase 2, open‐label, multicenter study

Abstract Background OB756 is a novel oral selective JAK2 inhibitor targeting the JAK‐STAT pathway. This study assessed its safety and efficacy in patients with essential thrombocythemia (ET) who were resistant to or intolerant of hydroxyurea or intolerant of interferon. Methods This phase 2, single‐arm, open‐label, multicenter clinical trial evaluated the efficacy and safety of OB756 in patients with ET who were intolerant of or resistant to hydroxyurea, or intolerant of interferon. The primary end point was the complete hematologic response (CHR) rate at week 24, whereas secondary end points included hematologic response (HR), the proportion of patients with ≥35% spleen volume reduction at week 24, molecular response, and safety. Results At week 24, the CHR was 22% (11 of 50) based on intention‐to‐treat analysis. Among evaluable patients, the HR rate reached 65.6% at week 24. At week 24, 94.7% of patients (36 of 38) experienced spleen volume reduction, with 50.0% achieving ≥35% reduction. Additionally, 74.2% of patients (23 of 31) had a ≥50% reduction in myeloproliferative neoplasm symptom assessment form total symptom score. Among evaluable patients, 84.7% (11 of 13) had a reduction in JAK2‐V617F allele burden post‐treatment. In terms of safety, most treatment‐related adverse events (TEAEs) were grade 1–2. Grade ≥3 hematologic TEAEs included anemia (10%) and neutropenia (6%). The incidence of grade ≥3 infections was 16% and grade ≥3 thrombotic events was 2%. Conclusions Overall, OB756 was well‐tolerated and demonstrated acceptable efficacy, offering a promising therapeutic option for ET patients who are resistant to or intolerant of hydroxyurea or intolerant of interferon.