“Anywhere that steroids are being used in clinical studies, especially randomized controlled studies, there is a place for the GTI.”
Paul Brunetta, MD is a physician and clinical researcher with 14 years of clinical care experience and 22 years of experience in the biotechnology industry in drug development. He currently serves as the Head of Clinical and Translational Science at Sana Biotechnology, which is advancing next-generation cell and gene therapies into the clinic. He is also a member of the Steritas Advisory Board.
As a physician graduating in 1990 – at the height of the AIDS pandemic in the pretreatment era – Dr Brunetta was drawn to the University of California San Francisco (UCSF) to complete his internal medicine training as it was famous for clinical research and providing excellent care to AIDS patients. He completed his fellowship in pulmonary and critical care and joined the faculty at UCSF focusing on thoracic oncology, tobacco-related lung disease and smoking cessation.
“I was fascinated by parallels between the AIDS pandemic and the tobacco-related disease global health crisis that had been going on for decades. After several years at UCSF, I moved into biotechnology where my interest in developing monoclonal antibody therapies led to experience implementing clinical trials across neurology, nephrology, rheumatology, immunology, pulmonary medicine, and solid organ transplantation.
During the early 2000s, there was a real boom in monoclonal antibody clinical research in autoimmune diseases - many of which were being treated with medications that included high-dose glucocorticoids and other effective but toxic drugs like cyclophosphamide.
One of the greatest benefits of these new therapies was their ability to reduce the need for corticosteroids. Unfortunately, steroid-toxicity was not well measured. Dr John Stone expressed a deep interest in helping Genentech design trials that reduced glucocorticoid exposure.”
It was during that collaboration that Dr Stone proposed the idea of the Glucocorticoid Toxicity Index (GTI). Dr Brunetta says it was the combination of Dr Stone’s inspiration and organizational brilliance to bring together sub-speciality experts from all around the world, and initial financial support from Genentech that led to the creation of the GTI.
“Steroids are used everywhere, and there's this impression that they’re highly effective, safe and inexpensive. They are one of the first things that physicians use, but the extent of their toxicity is rarely fully recognized.
Being able to reduce glucocorticoids is a huge benefit to patients as many of the toxicities can cause permanent damage such as joint destruction, diabetes or severe infections that can be fatal in at-risk patients.
Enabling teams like mine to develop new therapies that provide disease remission and reduce the risks associated with old therapies is what the GTI does. And that's why it's now being used in so many different diseases. These studies are going to generate a flood of steroid-toxicity data over the next three to five years - and that will make the GTI part of study standard practice whenever testing a new drug that reduces the need for glucocorticoids.”
Another area Dr Brunetta is excited about is the identification of patient groups that are at higher risk of steroid-toxicity-related adverse events. He believes this could lead to a push to try to get those at higher risk off of steroids as quickly as possible. He is also excited about the potential for measuring steroid-toxicity at point of care.
“In the last 20 years, clinical care has morphed into a relationship between the doctor, the patient and the computer or smartphone. The GTI-MD has the potential to interface with electronic medical record systems and provide reminders about what tests the patient should have and how steroid-toxicity should be measured and monitored.
One thing that isn’t discussed is how well patients in the real world comply with steroid tapers and how that impacts them - some of the things Steritas is working on could revolutionize our understanding here.”
Dr Brunetta stresses that measuring steroid-toxicity in drug development is more important than many biopharma companies recognize.
“It is much more important in the drug development space than many drug developers understand. It's important because it has to do with a patient's quality of life and risk of complications, so I'm pleased to see the GTI’s uptake in drug development has accelerated. Anywhere that steroids are being used in clinical studies, especially randomized controlled studies, there is a place for the GTI.”
Dr Paul Brunetta is a physician and clinical researcher with 14 years of clinical care experience and 22 years of experience in the biotechnology industry and drug development. He is a graduate of Johns Hopkins University in Baltimore and Tufts University School of Medicine in Boston. He went to the University of California San Francisco (UCSF) at the height of the AIDS epidemic and did his internship and medical residency at UCSF. Paul was Chief Medical Resident at San Francisco General Hospital (1993-1994) and then did his Pulmonary and Critical Care Fellowship at UCSF before joining faculty focusing on lung cancer, tobacco-related lung disease, and smoking cessation. He co-founded the Fontana Tobacco Treatment Center (FTTC) and has dedicated significant volunteer time to support FTTC expansion within the UCSF clinical system over the years. He recently co-authored the book Learning To Quit - a comprehensive guide to smoking cessation. Paul is a co-founder of Mobile Applications for Connected Health, a private company developing a comprehensive smoking cessation platform undergoing clinical research at the University of Colorado mHealth Impact Lab in the School of Public Health.
Paul joined the biotech industry in 2002 and has supported the approval of multiple monoclonal antibody therapies and has significant experience interacting with the FDA and EMA in the drug approval process. He has designed, monitored, and implemented trials in autoimmune drug development spanning phase I-IV trials across multiple diseases in neurology, nephrology, rheumatology, immunology, pulmonary medicine, and solid organ transplantation. His clinical research work has been published in the New England Journal of Medicine and other international specialty journals. Paul directed the Genentech Clinical Research Fellowship for 12 years, mentoring fellows across multiple disease areas. Paul joined Juno Therapeutics as SVP, Head of Translational Science in CAR-T development. He’s now Head of Clinical and Translational Science at Sana Biotechnology, which is advancing next-generation cell and gene therapies into the clinic.