A new era in cystic fibrosis treatment

As her health began to worsen in late 2017, Annette Quinn started measuring her declining lung function by making note of the number of days between episodes of hemoptysis, or coughing up blood. At first, the episodes occurred once every few months. But by the summer of 2018, Quinn experienced severe bleeding in her lungs every two weeks.

The frequent episodes, which required her to be hospitalized in June 2018, were caused by the progression of cystic fibrosis (CF), a genetic, life-threatening disease that causes thick mucus to build in the lungs, digestive tract, and other parts of the body. Quinn, who had remained in relatively good health since she was diagnosed with CF in 1994 at the age of 24, now required a high level of oxygen to walk and did not feel comfortable leaving the house. Although new therapies had proven to be effective in treating CF, Quinn—like many of the 30,000 people with CF in the United States—didn’t qualify because of her specific genetic mutations. She began to consider a lung transplant.

Then, in August 2019, Quinn’s health care team at Penn Medicine secured access, via the U.S. Food and Drug Administration’s compassionate use pathway, to an investigational therapy designed to treat CF. She started the therapy in early October.

“Suddenly, I could take a deep breath without coughing,” said Quinn, adding that she hasn’t experienced bleeding in her lungs since she started taking the therapy and requires less oxygen when she’s walking.

On October 21, the FDA approved the triple combination therapy, Trikafta, for patients 12 years and up with a type of genetic error called an F508del mutation – the most common CF mutation. Unlike the three previously approved therapies for CF, which targeted genetic mutations held by smaller segments of the CF population, the new therapy is designed to treat patients—like Quinn—who have the F508del mutation, effectively extending a new form of therapy to about 90 percent of CF patients.

“It represents a major breakthrough for the CF community,” said Denis Hadjiliadis, MD, PhD, director of Penn’s Adult Cystic Fibrosis program and an associate professor of Medicine. “The emergence of effective therapies fuels our hope that early treatment will not only lead to fewer complications and delay the progression of lung disease, but will also give patients like Annette a longer life, and one that they may live to their full potential.”

Evolution of CF Treatments

When Penn opened its Adult Cystic Fibrosis Program in the early 1990s, the life expectancy for a patient diagnosed with CF was their late 20s. Over the past 30 years, advances in screening and treatments have helped extend the average life expectancy and dramatically altered the therapeutic landscape for CF patients, who, until 2012, were all treated the same way.

Similar to Trikafta, the wave of previously approved therapies aims to improve the underlying cause of CF: a defective CF transmembrane conductance regulator (CFTR) gene. Every person has two copies of the CFTR gene—one inherited from each parent. Only people with mutations in both copies of the gene can develop CF. However, there are more than 2,000 different mutations in the CFTR gene that can cause CF, explained Gina Hong, MD, an assistant professor of Pulmonary Medicine and a member of the Adult Cystic Fibrosis and Bronchiectasis treatment team.

Research has shown that the first three cutting-edge treatments approved by the FDA have helped people with CF experience fewer flare-ups and hospitalizations, and led to an enhanced quality of life. However, the promising therapies were only helpful and effective for small segments of the CF patient population. For example, a drug called Kalydeco, which was approved in 2012, helps less than 10 percent people with CF.

Two studies, published in The New England Journal of Medicine and The Lancet in early November, found patients who received the newly approved therapy, Trikafta, showed improvement in a key measure of lung capacity.

“As a community, we are energized by the latest breakthrough and eagerly await transformational therapies for the rest of our patients,” said Hong, referring to the approximately 10 percent of CF patients whose mutations result in the production of virtually no CFTR protein, meaning there is nothing for current therapies to correct or activate.

While walking around in her New Jersey home, Quinn reflects on the past 25 years. In addition to the respiratory issues and severe lung infections, the thick mucus produced by the body also obstructs the digestive system, causing many patients—including Quinn—to struggle with malnutrition, bowel blockages, and diabetes. In recent years, the number—and variety—of doctor’s appointments has increased.

“The receptionist who answers the phone used to ask ‘Annette who?’ Now they say, ’Hey Annette,’” Quinn joked.

Her daily treatment regimen includes a host of medications, including enzymes to ensure her body absorbs enough nutrients, as well as the use of an inflatable vest—twice a day for 30 minutes—that vibrates at a high frequency, causing the chest to loosen and thin out the mucus. Since she started taking the therapy, her lung function has improved slightly, according to pulmonary function tests. But the biggest improvement, Quinn says, is to her quality of life.

She is looking forward to a family trip to Daytona Beach, Florida, this April to watch her daughter—who is set to graduate from Montclair State University in May—participate in the 2019 National Cheerleaders Association (NCA) College Nationals.

“This,” Quinn said, “will be the first time I will ever get to see her cheer in college.”

The material in this press release comes from the originating research organization. Content may be edited for style and length. Want more? Sign up for our daily email.