A clinical trial at UVM supports the U.S. Food and Drug Administration’s approval of new medication that will make self-care for people living with cystic fibrosis (CF) easier and more effective than other medications. Vanzacaftor / tezacaftor / deutivacaftor, produced by Vertex Pharmaceuticals Incorporated under the brand name Alyftrek, is the first CF drug that requires only once-daily dosing instead of the twice-daily dosing required by other CF drugs. It also has fewer side effects.

CF is a life-shortening, inherited condition affecting more than 92,000 people globally. It causes the cells to make mucus, sweat, and digestive juices that are thick and sticky instead of thin and slippery. These secretions end up blocking ducts, passageways, and tubes, especially in the lungs, digestive system, sweat glands, and reproductive tract. CF is caused by a malfunctioning protein resulting from mutations in a gene called a CF transmembrane conductance regulator (CFTR) gene. 

Treatments for CF include CFTR modulators, which are therapies designed to correct the malfunctioning protein. Alyftrek is a CFTR modulator. Additional therapies include mucus-thinning drugs, bronchodilators, chest physical therapy, breathing exercises, nutritional interventions, and surgical procedures to remove obstructions. 

Thomas Lahiri, M.D., professor of pediatrics, division chief for pediatric pulmonology, and director of the Pediatric Cystic Fibrosis Center at the UVM Children’s Hospital, and Charlotte Teneback, M.D., associate professor of medicine and director of the Adult Cystic Fibrosis Program at the UVM Medical Center, served as site principal investigators for this study at UVM and for other clinical trials that investigated the safety and efficacy of Alyftrek. Study participants included seven adults and two children with CF. Enrollment for these trials was highly competitive, and UVM was able to exceed its site expectations for enrollment, even keeping pace with larger cystic fibrosis centers. Enrollment began in 2023 and continues to the present with the follow-up phase.

“We have excellent enrollment in this study, which has allowed some local residents living with cystic fibrosis to have early access to the new medication,” says Teneback. Physicians are now prescribing Alyftrek for patients at the UVM Medical Center and UVM Children’s hospital. They are hopeful that the once-daily dosing will improve patient adherence.

The Cystic Fibrosis Clinical Research group at UVM is part of a large international network of clinical trial sites called the Cystic Fibrosis Therapeutics Development Network. Nearly every drug available for CF today is tested and brought to market through this network. The UVM researchers work with all phases of clinical trials and complete interventional as well as observational studies with both pediatric and adult participants. 

“There are research efforts to develop other CFTR modulators. There is also active research on gene editing and gene therapy, which could provide a cure for cystic fibrosis,” Lahiri says. “CFTR modulator therapy has been responsible for tremendous improvement in the overall health of people with CF and has led to remarkable increases in life expectancy, with median predicted survival now more than 60 years and climbing.”

“[This clinical trial at UVM] has allowed local residents living with cystic fibrosis to have early access to the new medication.” — Charlotte Teneback, M.D. 

The research team for the Vertex study at UVM includes Department of Pediatrics faculty Kelly Cowan, M.D., L. E. Faricy, M.D., and Keith Robinson, M.D., and pulmonary and critical care medicine assistant professor Zachary Weintraub, M.D., along with clinical coordinators from the Vermont Lung Center Vanessa Marascio, M.S., Abe Sender, PA-C, and Julie Sweet.

Research like this has contributed to the University of Vermont’s designation by the Carnegie Classification of Institutions of Higher Education as an R1 institution, placing it in the top tier of research universities in the U.S.