Beijing, March 2, 2022 —— InnoCare Pharma (HKEX: 09969), a leading biopharmaceutical company, announced today the Investigational New Drug (IND) approval of its Bruton’s tyrosine kinase (BTK) inhibitor orelabrutinib by China National Medical Products Administration (NMPA) to start phase II clinical trial in Neuromyelitis Optica Spectrum Disorder (NMOSD) in China.
This is a randomized, double-blind, placebo-controlled phase II clinical study evaluating the efficacy and safety of orelabrutinib in NMOSD patients.
Neuromyelitis optica spectrum disorder (NMOSD) is a chronic inflammatory demyelinating autoimmune disease of the central nervous system mainly involving the optic nerve and spinal cord, which are mediated by antigen-antibodies related to humoral immunity. Clinically, it is characterized by attacks of predominantly optic neuritis and longitudinally extensive transverse myelitis. One Chinese latest epidemiological study based on inpatients shows that the peak age-incidence of the disease is 45-65 years old, the incidence rate is 0.445/100,000 people per year, and the ratio of female to male is 4.71:1[i].
NMOSD is a highly relapsing, severely disabling disease. More than 90% of patients have relapses, about 60% within 1 year, 90% within 3 years. Most patients are left with severe visual impairment (blindness), limb dysfunction (paraplegia), and bowl and bladder dysfunction. Studies have shown that there is a clear correlation between functional disability and relapse in NMOSD patients, so it is necessary to seek new treatments to reduce relapse in patients.
The etiology and pathogenesis of NMOSD are not entirely clear. At present, it is considered to be related to a specific aquaporin 4 antibody (AQP4 IgG) produced by mature B cells, and up to 80% of patients are serologically AQP4 IgG positive[ii]. BTK is a key kinase in B cell receptor signal transduction pathway, which is responsible for regulating B cell proliferation, differentiation, maturation and cytokine expression. Abnormal activation of BTK-related signaling pathway can lead to autoantibody production and autoimmune diseases[iii]. Therefore, BTK can be developed as a new target for autoimmune diseases, including NMOSD, multiple sclerosis, systemic lupus erythematosus, etc.
Dr. Jasmine Cui, the co-founder, Chairwoman and CEO of InnoCare said, “It remains a challenge to seek efficient treatments for NMOSD, and there is still a large unmet medical need in reducing relapse and improving prognosis. Combining the pathogenesis of NMOSD with the orelabrutinib mechanism, we believe that orelabrutinib will bring a new treatment option for NMOSD.”
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 National Reimbursement Drug list to benefit more lymphoma patients.
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.
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.
[i] Tian, D. C., Li, Z., Yuan, M., Zhang, C., Gu, H., Wang, Y., and Shi, F. D. (2020). Incidence of neuromyelitis optica spectrum disorder (NMOSD) in China: A national population-based study. Lancet Reg Health West Pac 2, 100021.
[ii] Bennett, J. L., O'Connor, K. C., Bar-Or, A., Zamvil, S. S., Hemmer, B., Tedder, T. F., von Budingen, H. C., Stuve, O., Yeaman, M. R., Smith, T. J., and Stadelmann, C. (2015). B lymphocytes in neuromyelitis optica. Neurol Neuroimmunol Neuroinflamm 2, e104.
[iii] Kil, L. P., de Bruijn, M. J., van Nimwegen, M., Corneth, O. B., van Hamburg, J. P., Dingjan, G. M., Thaiss, F., Rimmelzwaan, G. F., Elewaut, D., Delsing, D., et al. (2012). Btk levels set the threshold for B-cell activation and negative selection of autoreactive B cells in mice. Blood 119, 3744-3756.