The Third China BioMed Innovation and Investment Conference was held at the Suzhou BioBay Conference Center on September 18, 2018. At the conference, Jiuzhang Biotech Company presented a special report titled “Review of Phase I Clinical Data and Prospect of Phase II Clinical Trial of Chlorogenic Acid for Injection, A Natural Small Molecular Innovative Drug, for Treatment of Brain Glioma “.
The Report scientifically presented and analyzed the biological characteristics, anti-tumor mechanism, Phase I clinical data (safety, pharmacokinetics, therapeutic trends) and special cases of chlorogenic acid, and briefly introduced the design and subsequent plan of Phase II/III clinical trials of chlorogenic acid for injection in treating recurrent Grade IV glioblastoma (GBM).
At present, the chlorogenic acid for injection has completed phase I clinical trial for use in treating advanced malignant brain gliomas and is going to have phase II clinical trial. Since 1999 when temozolomide was approved by the FDA for treating malignant brain glioma, the median survival from initial diagnosis to death in patients with malignant brain glioma was prolonged from the previous 12.1 months up to 14.6 months; for patients with recurrent high-grade (grade IV) brain glioma, the globally recognized median survival was 7.2-9.6 months; for patients with recurrent high-grade (grade IV) glioma who relapse for the second time and are refractory to international standard of care (progressed disease ), the globally recognized median survival was only 3-4.6 months. So far the data has not been rewritten, and there has been no breakthrough new drugs worldwide for 18 years.
All subjects with grade IV glioma were patients with multiple recurrences, and the median overall survival of subjects with grade IV glioma in the effective dose group (based on the time of receiving the randomly assigned drug) was up to 9.3 months, while in the literatures, the median overall survival of grade IV glioma patients with multiple recurrences was only 3 - 4.6 months. Furthermore, at the subsequent survival follow-up of subjects after ending the phase I trial, there was 1 patient achieving CR (complete response) and 1 patient achieving PR (partial response) according to RANO Criteria for Glioma Assessment. In the effective dose group (3 mg/kg group), as of September 10, 2018, among the patients who had completed the trial, the median OS in subjects with grade IV gliomas with multiple relapses (randomized medication calculated as the starting point) was up to 21.4 months; the median OS in subjects with grade III gliomas (randomized medication calculated as the starting point) was still ongoing. During the phase I trial, the survival benefit was significant in subjects with recurrent grade IV glioma with multiple relapses from the effective dose group.
In addition, all the adverse events that occurred to the enrolled subjects were disease progression related adverse events except infusion site reactions (muscular kerosis), indicating the extremely high safety of chlorogenic acid for injection.
Chlorogenic acid is a natural substance widely found in plants, which was discovered by British scholars in 1897. The research and development team of Jiuzhang Biotech has developed chlorogenic acid monomer as a drug for the first time in the world, conducted systematic preclinical studies, obtained independent intellectual property rights and applied it to the studies on the treatment of major diseases (cancers), and chlorogenic acid for injection is the world's first Class I anti-cancer new drug developed independently and with independent intellectual property rights.
The Institute of Materia Medica affiliated to Chinese Academy of Medical Science also confirmed that, the chlorogenic acid for injection was a small molecule natural immunomodulatory drug with multiple pathways, multi-targets and broad spectrum, mainly fighting against tumors by relieving immunosuppression and inducing tumor cell differentiation. On one hand, chlorogenic acid for injection can modulate targeted immune checkpoints, relieve immunosuppression and promote proliferation of CD4T lymphocytes; on the other hand, chlorogenic acid for injection can induce the differentiation of malignant tumor cells, making it transform from poorly differentiated status with higher malignancy to well differentiated status with lower malignancy. Especially in the nonclinical and clinical studies of malignant gliomas, it is found that chlorogenic acid for injection can penetrate through the blood-brain barrier and adjust the proportion of immune cells at the lesion site, facilitate the aggregation of tumor-killing M1 macrophages around the lesions, and inhibit the M2 type macrophages who help with the migration and proliferation of tumor cells, thus inhibiting the metastasis and proliferation of glioma. Relevant basic findings have been published in Scientific Reports.
Jiuzhang Biotech has provided systematic and comprehensive patent protection for chlorogenic acid for injection, including 28 domestic patents and 6 international patents granted, as well as 34 domestic patents and 24 international patents under substantive review. The Phase I/II Clinical Study on Innovative Class I New Drugs Chlorogenic Acid for Injection has been listed as a national science and technology major new drug discovery project in 13th Five-year plan.
In the near future, Jiuzhang Biotech will also sponsor a domestic multicenter phase Ⅱ clinical trial of brain glioma with Beijing Tiantan Hospital affiliated to Capital Medical University as the leading institute, striving to achieve rapid transformation into drugs in China.