Carla A. Frederick, MD, and Danielle M. Goetz, MD

Research by Carla A. Frederick, MD, left, and Danielle M. Goetz, MD, contributed to a new combination drug to treat cystic fibrosis.

Research Leads to Approval of Combination Drug to Treat CF

Published May 16, 2018

Research by Carla A. Frederick, MD, clinical assistant professor of medicine, and Danielle M. Goetz, MD, clinical associate professor of pediatrics, has helped lead to the approval of a new combination drug that treats the underlying cause of cystic fibrosis (CF).

“Every positive trial builds momentum toward other promising new therapies.”
Clinical assistant professor of medicine

Tezacaftor/Ivacaftor Offers ‘Hope’ to Patients

In February, the U.S. Food and Drug Administration approved the combination drug tezacaftor/ivacaftor — trade name Symdeko™ — which is a cystic fibrosis transmembrane conductance regulator (CFTR) modulator (corrects the CFTR protein).

“It means hope. There are lot of new therapies now available,” says Goetz, who specializes in pediatric pulmonology. “The goal is that there will be correctors for 93 percent of CF patients in the next five years and 100 percent in the next 10 years. So there will be some type of therapy directed at their specific mutations.”

Defective Gene Causes Buildup of Mucus

Cystic fibrosis is a progressive, genetic disease that causes persistent lung infections and limits the ability to breathe. For persons with CF, the defective CFTR gene leads to an abnormal CFTR protein channel, leading to a sticky buildup of mucus in the lungs, pancreas and other organs.

“For persons with CF, there’s a defect in the CFTR gene. That leads to an abnormal protein on the surface of cells. It causes problems with salt and water movement across cells, especially in the lungs and gastrointestinal tract,” Goetz says.

New Drug Combination Reduces Exacerbations

The drug is approved for persons 12 and over who have two copies of F508del — the most common CF mutation, making up 46 percent of the more than 30,000 persons with CF in the U.S. — as well as those 12 and over who have a copy of one of another 26 specified mutations of the key protein involved in CF.

In phase three clinical trials, people with two copies of the F508del mutation who took the combination drug had improved lung function by 4 percent compared to those taking a placebo. Those with at least one copy of the 26 specified mutations who took the combination drug in late-stage clinical trials had improved lung function by 6.8 percent compared to those taking a placebo.

Participants in the studies also experienced a 35 percent reduction in exacerbations — a sudden worsening of symptoms that requires treatment — and an increase in the measurement used to access quality of life. They were also less likely to experience tightness in the chest and potential drug interactions, which was observed in a subset of patients on the combination drug lumacaftor/ivacaftor (Orkambi™).

“This trial covered individuals who have a combination of two mutations and about 60 percent of individuals with CF will have access to this medication to improve their lung functions, decrease exacerbations and likely lengthen their lives,” says Frederick, who specializes in pulmonology and critical care.

Frederick, Goetz Are Co-Directors of CF Center

Frederick and Goetz are adult and pediatric center directors, respectively, of the Cystic Fibrosis Center of Western New York, which conducts therapeutic and observational clinical trials through the Cystic Fibrosis Foundation Therapeutics Development Network.

“Because the disease spans the transition from pediatric to adulthood, it’s good to have directors in both realms,” Frederick says. “Some of the trials are applicable to little kids, and some are for the older individuals.”

Triple Combination Therapy Trials on the Way

This approval paves the way for new, more effective triple combination therapies — treatments consisting of three different modulators, including tezacaftor and ivacaftor — scheduled to begin phase three trials this spring. 

“Every positive trial builds momentum toward other promising new therapies. That’s really what we saw with this trial,” Frederick says. “It’s an important stepping stone to therapies that are going to be available for most individuals with CF in the near future.”

Three registered nurses — Nadine Caci, Christine Roach and Beth Cahill — took part in the research. Caci was the primary research coordinator for this trial, while Roach is the primary research coordinator for the upcoming study.

Tezacaftor/ivacaftor was developed by Vertex Pharmaceuticals Inc. with clinical, scientific and funding support from the Cystic Fibrosis Foundation.