Beijing, Dec. 13, 2021——InnoCare Pharma (HKEX: 09969), a leading biotech company, announced today that leading PIs presented latest data of BTK inhibitor orelabrutinib at the 63rd American Society of Hematology (ASH) Annual Meeting on December 11-14, 2021, which is hold online and offline in Atlanta, Georgia.
The study in patients with relapsed or refractory (r/r) Waldenstrom’s Macroglobulinemia, led by Professor Daobin Zhou, is selected as oral presentation, and the study in patients with r/r Chronic Lymphocytic Leukemia/Small Cell Leukemia, led by Professor Jianyong Li, and the study with orelabrutinib in the treatment of Primary Immune Thrombocytopenia, led by Professor Ming Hou, are selected as posters.
Efficacy and Safety of Orelabrutinib in Relapsed/Refractory Waldenstrom’s Macroglobulinemia Patients
This study is aimed to evaluate the efficacy and safety of orelabrutinib for the treatment of R/R WM patients. The primary endpoint was major response rate (MRR) as assessed by IRC. Key secondary endpoints were MRR as assessed by investigator, overall response rate (ORR), duration of major response (DOMR), progression-free survival (PFS), OS, etc.
With a median duration of treatment of 13.67 months, MRR was 78.7% as assessed by investigator. ORR was 87.2%. The estimated 12-month DOMR was 91.3%. The estimated 12-month PFS and OS were 89.3% and 93.6%, respectively. The median PFS and median OS have not been reached.
The most commonly reported adverse events (AE) were thrombocytopenia, neutropenia, leukopenia, upper respiratory infection. There was no reported grade ≥3 atrial fibrillation and/or atrial flutter, or grade ≥3 diarrhea.
Professor Daobin Zhou commented that “Orelabrutinib has demonstrated substantial efficacy in treating r/r WM patients under short-term follow-up period. It has shown favorable safety and tolerability profile. It has the potential to be a promising treatment option for r/r WM patients.”
Poster Presentation 1：
Orelabrutinib Monotherapy in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: Updated Long Term Results of Phase II Study
A total of 80 patients with R/R CLL/SLL were enrolled. The median follow-up time was 33.1 months, with 67.5% remaining on study treatment.
The overall response rate (ORR) was 93.8 % with 26.3% CR/CRi as assessed by investigator. Median time for achieving first response was 1.84 months. The median duration of response (DOR) and progression-free survival (PFS) were not reached. The estimated 30-month DOR and PFS were 67.2% and 69.7% respectively by investigator assessed.
Orelabrutinib showed a significant higher CR/CRi rate in R/R CLL/SLL in comparison with other BTK inhibitors at a similar median follow-up period.
Extended follow-up demonstrated that there were no emerging safety concerns. Similar to the previous reported safety results, most AEs were mild to moderate.
Professor Wei Xu commented that “This updated study result further confirms that orelabrutinib is efficacious in treating R/R CLL patients with significant higher CR rate than other BTK inhibitors, durable response and improved safety profiles. Orelabrutinib provides a favorable therapeutic choice for patients with R/R CLL/SLL and has great potential to be the best candidate for the combination therapy.”
Poster Presentation 2：
Orelabrutinib, a Selective Bruton’s Tyrosine Kinase (BTK) Inhibitor in the Treatment of Primary Immune Thrombocytopenia (ITP)
Primary immune thrombocytopenia (ITP) is the most common autoimmune hemorrhagic disorder characterized by decreased platelet count, increased risk of bleeding, and poor quality of life. Only about 70% patients response to first-line treatments, some patients are still refractory or relapsed after combined therapies, therefore it is necessary to explore new therapeutic targets. Bruton’s tyrosine kinase (BTK) is a non-receptor tyrosine kinase of Tec family, which is widely expressed in hematopoietic cells including B cells, monocytes/macrophages, and others. Inhibition of BTK may reduce platelet destruction by inhibiting B cell activation and autoantibody production. Orelabrutinib is a new generation of BTK inhibitor which has been used in hematological malignancies, this is the first study to explore the mechanisms of orelabrutinib in the treatment of ITP.
In a vitro study utilizing peripheral blood of ITP patients, Orelabrutinib significantly inhibited the expression of the activation markers CD69 and CD86 of the BCR signaling pathway on B cells, and also significantly decreased the number of CD138+ plasma cells.
In the active ITP murine models, platelet count was significantly higher in orelabrutinib treated mice than that of control mice at days 14, 21, 28 after splenocyte transfusion. The frequency of total B cells in peripheral blood leukocytes, the proportion of GL-7+ germinal center B cells and plasma cells in splenocytes were all lower in mice treated with orelabrutinib than that of the control group.
Professor Ming Hou commented that ”Orelabrutinib could effectively suppress the activation and differentiation of B cells in vitro and in vivo, thus alleviate the thrombocytopenia in active ITP murine models. It could be the new treatment strategy for refractory/relapsed ITP patients.”
Orelabrutinib is a small molecule Bruton’s tyrosine kinase inhibitor (BTKi) developed for the treatment of cancer and autoimmune diseases.
Orelabrutinib had received approval on Dec. 25, 2020 from the China National Medical Products Administration (NMPA) in two indications: the treatment of patients with r/r Chronic Lymphocytic Leukemia (CLL) /Small Lymphocytic Lymphoma (SLL), and the treatment of patients with r/r Mantle Cell Lymphoma (MCL). In addition, multi-center, multi-indication clinical trials are underway in the US and China for orelabrutinib as monotherapy or in combination therapies for the treatment of Marginal Zone Lymphoma (MZL), Central Nervous System Lymphoma (CNSL), Waldenstrom’s Macroglobulinemia (WM), Diffuse large B-cell lymphoma (DLBCL), etc.
Orelabrutinib was granted as Breakthrough Therapy Designation for the treatment of r/r MCL by U.S. Food and Drug Administration (FDA).
Attributed to its excellent selectivity and clinical safety profiles, orelabrutinib is also evaluated in the global phase II studies for the treatment of Multiple Sclerosis (MS), phase II clinical trials for the treatment of Systemic Lupus Erythematosus (SLE) and Primary Immune Thrombocytopenia (ITP) in China.
InnoCare is a commercial stage biopharmaceutical company committed to discovering, developing, and commercializing first-in-class and/or best-in-class drugs for the treatment of cancer and autoimmune diseases. We strategically focus on lymphoma, solid tumors, and autoimmune diseases with high unmet medical needs in China and worldwide. InnoCare has branches in Beijing, Nanjing, Shanghai, Guangzhou, Hong Kong, New Jersey and Boston.