NASH (Nonalcoholic Steatohepatitis) is a chronic liver disease that has gained significant attention from the pharmaceutical industry and clinical societies in the last decade. In this webinar, Dimitar Tonev, a trained hepatologist and an expert in chronic liver diseases, chatted with Patrick Short, CEO of Sano Genetics, to provide insights into the challenges and opportunities in developing drugs for NASH.
The link to the full webinar is here; a brief summary is below for easy reference.
Dr. Patrick Short, PhD is the Co-founder and CEO of Sano Genetics. Sano’s platform helps clinical development teams to move 10x faster at 5x lower cost by automating entire workflows for protocols, consent, prescreening, genetic testing, and matchmaking with trial sites.
Dimitar Tonev is a hepatologist with over 23 years of experience specialising in innovations and disease-modifying therapies in NASH. He has worked for various companies in the pharmaceutical, diagnostic, and device industries, and is currently a consultant for liver disease drug development.
One of the biggest challenges in developing drugs for NASH is the recruitment of patients for clinical trials. Patients with advanced NASH, who are the ideal candidates for clinical trials, are already under the care of hepatologists. However, patients with F2 and F3 fibrosis, which are common clinical trial eligibility criteria based on regulatory guidance, are predominantly treated by general practitioners or endocrinologists and are not typically diagnosed with NASH. Therefore, clinical trials need to consider the role of referring physicians to build a network around a hepatology unit with high-risk patients' specific features.
Another significant issue is patients' lack of knowledge about NASH, which makes them hesitant to participate in clinical trials. Patients are usually surprised to learn that they have NASH and need a clinical trial to take care of their liver health. Additionally, for researchers, clinical trials can be labor-intensive, and academic hepatologists do not have enough time to dedicate to them. Commercial research units, which only focus on clinical research, are more successful in clinical trial patient recruitment.
The transition from liver biopsy to non-invasive biomarkers is the future of early detection of NASH. Tonev mentioned that the Scottish NHS is automatically triggering an investigation of patients with liver abnormalities considered high-risk for NASH, such as elevated transaminases, high-risk diabetes type 2, and obesity, using liver panels. This biochemical abnormality will flag the patient to be referred to hepatology.
In addition, there are highly anticipated results coming from clinical trials that are still open in phase three. The frontrunners include Madrigal, which has one of the most effective agents in terms of hitting the two potential histological endpoints, namely NASH resolution and improvement of fibrosis. The second family of agents that is frequently considered a potential frontrunner is FXR agonists, including bettycolic acid, which has already been registered for PBC. The third family of agents is P-par agonists, such as inventiva's Juana Fibronur.
Finally, Tonev anticipates that genetically-targeted therapies will become increasingly important in the future. Although these agents have not been in the spotlight, they are well advanced and have already been successful in treating other liver diseases. Tonev believes that as we move into more a more precise drug development process in NASH, genetic testing and predispositions of patients will be important when selecting patients for clinical trials.
The challenges in developing drugs for NASH are significant, but several potential treatment options still in clinical trials are showing great promise. Non-invasive biomarkers and more involvement from referring physicians are the future of early detection of NASH. Finally, precision medicine and genetically-targeted therapies will become increasingly important in the future.