Trikafta Will Be ‘Life-Transforming,’ Especially for Younger CF Patients, Researchers Say

Trikafta is expected to be a “game-changing” therapy for cystic fibrosis (CF), especially for younger patients, say researchers at Children’s Hospital of Richmond at Virginia Commonwealth University (VCU), who were involved in Trikafta trials where marked improvements were seen in patients taking the therapy.

The medicine, developed by Vertex Pharmaceuticals, is a next-generation triple combination treatment consisting of three modulators — elexacaftor, tezacaftor, and ivacaftor — to address the defects in the CF transmembrane conductance regulator, or CFTR protein, that underly the disease.

Trikafta is approved for patients ages 12 and older, with at least one F508del mutation in the CFTR gene — criteria that include nearly 90% of CF patients.

The news of Trikafta’s approval in October 2019 was especially thrilling for patients like Anna Thompson, a 15-year-old girl who has been followed at the Children’s Hospital of Richmond since she was diagnosed with CF, six days after her birth.

Until recently, she had no therapeutic options for her specific CF mutation. Only patients with rarer CFTR mutations qualified for the therapies available, but Trikafta is expected to dramatically change that and expand treatment to nearly all CF patients.

Anna has been taking Trikafta tablets for three weeks now, and is doing well. Her daily treatment includes medications, pancreatic enzymes, nebulizer treatments, and chest physical therapy with a vest. On top of that, she also needs to monitor her weight and follow a high-calorie diet.

“You wouldn’t know anything is wrong with her if you met her,” Eddie Thompson, her father, said in a press release. “She’s been really good and responsible about keeping her treatments up. She’s been a relatively healthy cystic fibrosis patient.”

Trikafta’s approval was based on two Phase 3 clinical trials — AURORA F/MF (NCT03525444), which tested the treatment in patients with one F508del mutation and one minimal function mutation, and AURORA F/F (NCT03525548), which evaluated Trikafta in patients with two F508del mutations.

These studies were “built on a lot of research,” said Joel Schmidt, MD, director of the pediatric program at the Cystic Fibrosis Center at Children’s Hospital of Richmond, and a principal investigator in the AURORA F/F trial.

His hospital was one of the 44 centers in four countries (U.S., Belgium, Netherlands, and U.K.) joining the study.

During the trials, some patients had impressive results with Trikafta treatment, including an average improvement of 10% to 13% in lung function. This is unprecedented for CF patients, the researchers noted.

The treatment also reduced the levels of salt in the patients’ sweat (a gold standard measure of the disease), improved their body mass index (BMI), and relieved respiratory symptoms.

“One patient that started the drug six weeks ago in a compassionate use program before the FDA approval was getting ready for a transplant,” Schmidt said. “After six weeks, she was no longer on the transplant list. Patients also reported better quality of life on the medicine.”

Ryan Hayden, clinical research and lead coordinator in Trikafta’s trials, said, however, that the medicine is not “a one-time cure,” as it does not repair the inherited mutations causing the disease, “but rather dramatically improves the functioning of the mutated … proteins.”

“Patients are feeling better and getting sick less,” he said.

Hayden, together with Meg Lessard, a senior clinical research coordinator in the Pediatric Research Office at Children’s Hospital of Richmond, have been assessing patients who are receiving Trikafta.

“We make sure the research protocol is being followed for patient safety and to ensure data quality,” Lessard said.

“The hope is to extend trials to even younger children in order to improve and preserve lung function early on in life,” she added.

With that purpose, a Phase 3 clinical trial (NCT03691779) is underway to evaluate the safety, tolerability, efficacy, and biological effects of Trikafta in younger CF patients, ages 6 to 11. Recruitment for the study is currently open. Information about contacts and locations can be found here.

“The CF patient that is born today will be living a normal life and have a better quality of life,” Schmidt said. “This drug will be life transforming, especially for younger patients. This is game-changing.”