ST. LOUIS — Researchers from Saint Louis University’s School of Medicine, in collaboration with Arrowhead Pharmaceuticals and Takeda Pharmaceuticals, report the first effective drug for the treatment of a rare, genetic liver disease that previously could only be treated with a liver transplant.
The study, “Fazirsiran for Liver Disease Associated with Alpha1-Antitrypsin Deficiency,” was published online in the New England Journal of Medicineone of the world’s leading medical journals.
The multicenter, phase 2, open-label study investigated the safety and efficacy of fazirsiran, an RNA interference drug, in patients aged 18 to 75 years with liver disease associated with alpha-1 antitrypsin (AAT) deficiency. AAT is a protein made in the liver and released into the blood in large amounts to help protect the body in fighting infection.
Jeffrey Teckman, MD, professor of pediatrics and biochemistry and molecular biology, is the senior author of the paper.
“This is the culmination of more than a decade of work to cure this disease, and a significant amount of work has been done here,” said Teckman, who is also director of pediatric gastroenterology and hepatology at SLU. “We’ve had patients come across the country to see SLU’s expert faculty at SSM Health Cardinal Glennon Children’s Hospital with this disease for care and to participate in our studies.”
Teckman is a leading authority on AAT deficiency, which affects 1 in 3,500 births and causes severe lung disease in adults or liver disease in adults and children. Symptoms may include shortness of breath and wheezing, repeated lung infections, yellow skin, fatigue, liver cirrhosis, liver failure, and even death.
Teckman says those affected by the disease are often undiagnosed or misdiagnosed as having fatty liver, asthma or smoking-related lung disease. The diagnosis can be suspected by finding low levels of AAT in the blood and confirmed by genetic testing.
“When I was in medical school, I learned that reducing liver fibrosis, or scar tissue in the liver, was impossible with AAT deficiency, but now we see that we can reverse this process in humans with minimal side effects,” Teckman said.
Longtime collaborator Arrowhead Pharmaceuticals used technology during the trial that allowed doctors to turn off one gene in the human liver with almost no side effects.
“In this case, we chose to shut down the abnormal alpha-1 antitrypsin gene in the liver, and the new drug can do that effectively, stopping the disease and allowing the liver to heal,” Teckman said.
Next, the team will expand the international study to additional adult patients and children in collaboration with Takeda Pharmaceuticals.
Arrowhead Pharmaceuticals supported this work. Strnad is supported by the German Research Foundation (DFG) (grant STR1095/6-1) and by the DFG consortium CRC/SFB 1382 “Gut-lever axis” (ID 403224013). Teckman is supported for this work by Arrowhead Pharmaceuticals, Takeda and The Alpha-1 Foundation.
Other authors include Pavel Strnad, MD, Department of Internal Medicine III, University Hospital; Christian Trautwein, MD, Department of Internal Medicine III, University Hospital; Mattias Mandorfer, MD, Ph.D., Department of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna; Gourab Choudhury, MD, Department of Respiratory Medicine, Royal Infirmary of Edinburgh University Hospital, University of Edinburgh, Edinburgh; William Griffiths, MD, Department of Hepatology, Addenbrooke’s Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge; Rohit Loomba, MD, Division of Gastroenterology, University of California San Diego School of Medicine; Thomas Schluep, Sc.D., Ting Chang, Ph.D., Min Yi, Ph.D., Bruce D. Given, MD, James C. Hamilton, MD, and Javier San Martin, MD, Arrowhead Pharmaceuticals.
Saint Louis University School of Medicine
Founded in 1836, Saint Louis University School of Medicine has the distinction of awarding the first medical degree west of the Mississippi River. The school trains physicians and biomedical scientists, conducts medical research and provides health care at the local, national and international levels. Research at the school seeks new cures and treatments in five key areas: cancer, liver disease, heart/lung disease, aging and brain disease, and infectious diseases.
New England Journal of Medicine
Fazirsiran for liver disease associated with alpha1-antitrypsin deficiency
Article publication date
Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of any press releases posted on EurekAlert! by sponsoring institutions or for the use of information through the EurekAlert system.