Malignant mesothelioma is a rare type of cancer that is characterised by tumor formation in the mesothelium, a tissue layer that covers the pleural organs such as heart, abdomen, lungs and other organs. The biggest risk factor of the disease is exposure to asbestos, a silicate mineral. Some of the major symptoms of the disease include cough, shortness of breath and pain in the chest. The symptoms in malignant mesothelioma could take as long as 30 to 50 years to show. Surgery, chemotherapy and radiotherapy are some of the major options available for the treatment of malignant mesothelioma. The prevalence of the disease is not known; however, it is estimated that malignant mesothelioma accounts for approximately 1% of all cancers globally. According to the cancer research, in the U.K., 48% cases of malignant mesothelioma are of people above the age of 75 years.
The therapeutics pipeline for malignant mesothelioma is expected to witness considerable growth in the near future on account of increasing exposure of general population to pollutants such as asbestos as a result of rising level of pollution in the environment, eventually leading to increasing prevalence of the disease. Other factors that are expected to contribute to the growth in the therapeutics pipeline of malignant mesothelioma include poor prognosis of the disease, growing healthcare investment on cancer treatments and rising geriatric population.
A number of companies are engaged in the research and development of therapeutics for malignant mesothelioma with some very promising drug candidates in the pipeline. In October 2016, Polaris Pharmaceuticals, Inc. initiated a Phase II / Phase III study in subjects with malignant pleural mesothelioma with low argininosuccinate synthase (ASS1) expression to assess ADI-PEG 20 with pemetrexed and cisplatin. The study is ongoing and is expected to be completed in June 2018. ADI-PEG 20 is a biologic under clinical investigation to treat cancers. The mechanism of action of ADI-PEG 20 involves blocking of external supply of arginine, leading to death of arginine-dependent cancer cells, while patient’s normal cells are unharmed. In April 2017, AstraZeneca plc commenced a Phase II study of durvalumab in combination with tremelimumab in malignant pleural mesothelioma. Durvalumab is a human monoclonal antibody which is a programmed death ligand-1 (PD-L1) inhibitor. Tremelimumab is an anti-CTLA-4 antibody that enhances the immune response against cancer cells by blocking the activity of CTLA-4. Tremelimumab was granted an Orphan Drug Designation by the USFDA for the treatment of malignant mesothelioma in 2015. Additionally, many promising drug candidates including trabectedin by PharmaMar S.A., tazemetostat by Epizyme, Inc., nivolumab and ipilimumab by Bristol-Myers Squibb Company, vinorelbine by Laboratoires Pierre Fabre and nintedanib by Boehringer Ingelheim GmbH, Epizyme, Inc are in the late stage of development in the pipeline of malignant mesothelioma. Many companies have adopted the approach of co-development of drug candidates for malignant mesothelioma. In July 2014, Bristol-Myers Squibb Company and Ono Pharmaceutical Co., Ltd. of Japan entered into a strategic collaboration for the joint development and commercialization of various immunotherapies as mono and combination therapies for the treatment of cancer in Japan, South Korea and Taiwan.
Some of the major players involved in the development of therapeutics for the treatment of malignant mesothelioma include AstraZeneca plc, Boehringer Ingelheim GmbH, Polaris Pharmaceuticals, Inc., PharmaMar S.A., Bristol-Myers Squibb Company, Ono Pharmaceutical Co., Ltd., Bayer AG, Aduro Biotech, Inc., Calithera Biosciences, Inc., CBT Pharmaceuticals, Inc.