The American Journal of Hematology recently published the results of a phase II study of BTK (Bruton Tyrosine Kinase) inhibitor orelabrutinib in patients with patients with persistent or chronic primary immune thrombocytopenia (ITP), which evaluated the efficacy and safety of orelabrutinib in adult patients with persistent or chronic ITP. The journal concluded that the study provides compelling evidence for the potential of orelabrutinib as a safe and effective therapy for patients with ITP.

The primary endpoint of the study was the proportion of patients achieving platelet counts of ≥50?×?109/L for at least two consecutive weeks (without rescue medication in the prior 4 weeks). A total of 33 patients were enrolled. Both the 50mg QD and 30mg QD dose cohorts of orelabrutinib were safe in the treatment of patients with ITP. Generally, patients taking orelabrutinib at the 50mg QD dose responded rapidly with better efficacy, especially in those who had previously responded to glucocorticoids (GC) / intravenous immunoglobulin (IVIG) therapies.

In the 50mg group, 40% patients reached primary endpoint. Among the 12 patients achieving primary endpoint response, the sustained response rate was 83.3%. Among the 22 patients with previous response to GC or IVIG, 75.0% at the 50mg arm achieved the primary endpoint..

The use of orelabrutinib significantly improved patients' quality of life. At week 24, patients saw an average increase of 21.2 points in physical well-being and 10.3 points in emotional well-being, as measured using the 36-Item Short Form Health Survey (SF-36). These results illuminate the potential of orelabrutinib to positively transform overall health perceptions and daily living for patients.

In a concise analysis of 28 patients, orelabrutinib displayed dose-dependent PK. Notably, the 50?mg dose resulted in significantly higher drug exposure. Both doses achieved near complete and sustained occupancy of the target molecule, BTK. Median occupancy exceeded 99% four?hours after administration, remaining above 93% throughout the 24-hour dosing interval. These findings not only confirm dose-dependent exposure but also highlight the robust target engagement potential of orelabrutinib across both dosage levels, underscoring its potential therapeutic efficacy.

Orelabrutinib was safe and well tolerated in the treatment of ITP. Most treatment related adverse events (TRAEs) were grade 1 or 2.

Professor Ming Hou, the leading PI, said, "The phase 2 study provides compelling evidence for the potential of orelabrutinib as a safe and effective therapy for patients with ITP. Further investigation through larger, randomized, placebo-controlled trials is warranted to definitively confirm these findings and establish orelabrutinib as a valuable treatment option for ITP management."

A phase III registrational trial of orelabrutinib for the treatment of patients with ITP is underway in China. The last patient is expected to be enrolled by the end of 2024.

The American Journal of Hematology is an academic journal focusing on hematology, which was founded in 1976 and published monthly by WILEY publisher. The journal has been included in SCIE and SCI databases, with an impact factor of 13.268 in 2022.

About Orelabrutinib

Orelabrutinib is a highly selective BTK inhibitor developed by InnoCare for the treatment of cancers and autoimmune diseases.

On Dec. 25, 2020, orelabrutinib received approval from the China National Medical Products Administration (NMPA) in two indications: the treatment of patients with relapsed/refractory chronic lymphocytic leukemia (CLL) /small lymphocytic lymphoma (SLL) and the treatment of patients with relapsed/refractory mantle cell lymphoma (MCL). At the end of 2021, orelabrutinib was included into the National Reimbursement Drug list, allowing it to benefit more lymphoma patients. On Nov. 22, 2022, orelabrutinib was approved for the treatment of R/R MCL in Singapore. On April 20, 2023, orelabrutinib was approved for the treatment r/r MZL in China.

In addition to the approved indications, multi-center, multi-indication clinical trials are underway in the US and China with orelabrutinib as monotherapy or in combination therapies, such as for the first line treatment of MCD subtype of diffuse large B-cell lymphoma (DLBCL).

Orelabrutinib was granted Breakthrough Therapy Designation for the treatment of r/r MCL by U.S. Food and Drug Administration (FDA). Patient enrollment of the phase II registrational trial for R/R MCL was completed in the U.S. The Company expects to submit the NDA to the U.S. Food and Drug Administration (US FDA) in the third quarter of 2024.

In addition, orelabrutinib is being advanced in other autoimmune trials, worldwide, including: a phase III registrational trial for the treatment of primary immune thrombocytopenia purpura (ITP) ongoing in China, a global phase II study for the treatment of Multiple Sclerosis (MS), a phase II study for the treatment of SLE in China that has achieved proof of concept (PoC), and a phase II study for the treatment of Neuromyelitis Optica Spectrum Disorder (NMOSD) ongoing in China.