A recent study published in the Journal of American Hematology presents phase II clinical trial results of orelabrutinib, a Bruton’s tyrosine kinase (BTK) inhibitor, for treating chronic primary immune thrombocytopenia (ITP). The study indicates that orelabrutinib could offer a safe and effective treatment option for ITP patients.
The research aimed to assess the efficacy and safety of orelabrutinib in adults with chronic ITP. The primary endpoint was the proportion of patients achieving a platelet count of at least 50×10^9/L for a minimum of two consecutive weeks without the need for rescue medication during the first four weeks. A total of 33 patients were enrolled. Orelabrutinib demonstrated good safety profiles in two dosing groups, 50 mg and 30 mg taken orally once daily. The 50 mg dose showed quicker and better effectiveness, especially in patients previously responsive to glucocorticoids (GC) or intravenous immunoglobulin (IVIG).
In the 50 mg group, 40% of patients met the primary endpoint. Of the 12 patients achieving this endpoint, 83.3% maintained a sustained response. Among the 22 patients previously responsive to GC or IVIG, 75.0% in the 50 mg group reached the primary endpoint.
Researchers reported that by the 24th week, the SF-36 health survey showed an average increase of 21.2 points in physical health scores and 10.3 points in mental health scores. This suggests that orelabrutinib could significantly enhance patients' daily life and overall well-being.
An analysis of 28 patients showed that orelabrutinib displays dose-dependent pharmacokinetics (PK). Both dosages almost fully and continuously occupied the target molecule BTK, with the 50 mg group showing higher drug exposure. Four hours post-administration, the median occupancy rate exceeded 99% and maintained above 93% throughout the 24-hour dosing period. These findings not only demonstrate the dose-dependency of drug exposure but also highlight the strong target occupancy potential of orelabrutinib at both dosages, underlining its potential efficacy.
Professor Hou Ming, Head of Hematology at Shandong University Qilu Hospital and the study's lead investigator, stated, “Phase II results show that orelabrutinib could provide a safe and effective treatment option for ITP patients. We are planning larger-scale randomized placebo-controlled trials to definitively establish orelabrutinib as an ideal treatment choice for ITP patients.”
The phase III registration clinical trial for orelabrutinib in ITP patients is accelerating and expected to complete patient enrollment by the end of 2024.
Related publication information: http://doi.org/10.1002/ajh.27303.
