The First Russian Targeted Therapy Drug Developed with the Support of Skolkovo Foundation Has Entered the Clinical Trial Stage in Oncology
The Ministry of Healthcare of the Russian Federation has approved the conduct of the clinical trial to evaluate safety and preliminary efficacy of alofanib which is the first Russian targeted agent in oncology. Alofanib will be studied in gastric cancer patients who have exhausted other standard treatment options.
Alofanib was developed by a Russian company “Russian Pharmaceutical Technologies” ("Ruspharmtech", St. Petersburg). The company has created an innovative Russian drug with the support of Skolkovo Foundation. Alofanib is the world’s first drug from a class of allosteric inhibitors of the fibroblast growth factor receptor 2 (FGFR2).
Photo by "Ruspharmtech.
Many types of the tumor cells including gastric cancer cells express the FGFR2 receptor on their surface. The receptor activation results in the cell reproduction, tumor growth and metastases. Unlike existing inhibitors that work inside the cell alofanib blocks the part of the receptor that is located outside of the cell, convoluting the receptor which results in its deactivation. This mechanism allows for affecting the receptor regardless of various FGFR isoforms that may appear (whereas monoclonal antibodies become no longer effective in this situation) and despite new mutations that result in treatment resistance of a tumor cell (whereas tyrosine kinase inhibitors become no longer effective in this situation). This mechanism of action was deemed innovative and was patented by “Ruspharmtech” in Russia, EEU countries, USA, European Union, Japan and China.
The results of the preclinical studies published in the recognized international journals, such as European Journal of Cancer, Medicinal Chemistry and Investigational New Drugs, demonstrate the need of further research of the drug in the clinical trials. Currently there is a start of the phase 1b clinical trial in patients with metastatic gastric cancer for whom the standard treatment options proved to be ineffective. The study will be conducted in Moscow, St. Petersburg, Omsk and Rostov-on-Don.
Figure illustrating the mechanism of action.
On a tumor cell alofanib binds to the outside part of the fibroblast growth factor receptor 2, convoluting the receptor which results in itsdeactivation and stops the tumor cell reproduction.
"Gastric cancer is an important medical and social problem in Russia,- says Prof. Sergei Tjulandin, Chairman of the Russian Society of Clinical Oncology, Deputy Director of the N.N. Blokhin Russian Cancer Research Center of the Ministry of Health of the Russian Federation. – This type of tumor has been the 4th and 6th most prevalent cancer in men and women, respectively, with over 37,000 new cases ofgastric cancers each year. Unfortunately once metastases appear our treatment options become very limited. Life expectancy of such patients is about 1 year".
Ilya Tsimafeyeu, fellow inventor, making a presentation on alofanib at ESMO Asia 2016 congress. Photo by “Ruspharmtech”.
“The Skolkovo Foundation has been actively supporting the development of targeted therapy that affect a specific target within tumors”, – says senior vice-president for innovations in Skolkovo Foundation, Kirill Kaem. – "New types of inhibitors can result in dramatic changes and affect the patient's life expectancy, which is already happening in case of lung cancer, breast cancer, kidney cancer and other tumors. The first Russian targeted drug has successfully passed a number of extended preclinical trials in accordance with international requirements and will enter the first stage of the clinical trials to be studied in gastric cancer patients. The Grants Committee of the Foundation made a decision on further support of our project".
The research organization "Russian Pharmaceutical Technologies" was founded in April 2012 by a group of scientists with the objective to discover, study and commercialize new drugs and innovative drug design technologies as well as to seek for new treatment approaches in oncology and other fields of medicine. The first and most important project was the development of alofanib, an allosteric inhibitor of the fibroblast growth factor receptor 2. Since 2012 the company has been a resident of the Skolkovo Foundation. Preclinical studies were performed with a support of the research grant provided by the Foundation.