New Drug Therapy Shows Promise for Cystic Fibrosis

By Cari Wade Gervin
Thursday, May 14, 2020

An FDA-approved drug cocktail may provide improvement for many patients with this common hereditary disease.

Around 90% of cystic fibrosis patients could show dramatic improvement with a newly approved drug therapy. Called Trikafta, the three-drug combination was approved by the FDA in October 2019 and has been hailed as a breakthrough for cystic fibrosis treatment.

“This milestone is the result of an extraordinary community working together against great odds, and we are overjoyed that this will mean more people will have effective treatments for their disease,” says Preston W. Campbell III, MD, President and CEO of the Cystic Fibrosis Foundation (CFF), in a press release.

The drug therapy is the first approved by the FDA for cystic fibrosis patients with at least one F508del mutation, which is about 90% of cystic fibrosis patients. It has only been approved for those ages 12 and older; clinical trials to assess the safety for younger patients are underway.

A 10% to 14% improvement

Trikafta consists of three different cystic fibrosis transmembrane conductance regulator (CFTR) modulators — elexacaftor combined with tezacaftor/ivacaftor (Symdeko). Although the two-drug combination has already been in use for cystic fibrosis patients, drug trials for Trikafta showed a 10% increase from baseline in percent predicted forced expiratory volume in one second (ppFEV1) for patients with two copies of the F508del mutation, compared to patients taking only Symdeko. A different trial showed an increased mean ppFEV1 13.8% from baseline for patients with one copy of the F508del mutation compared to patients taking a placebo.

The latter trial also showed patients taking Trikafta had reduced chloride levels in their sweat, lower BMIs and a decreased number of pulmonary exacerbations.

Are the Downsides worth it?

Young cystic fibrosis patients and their parents have hailed the drug therapy as a game changer. While the drug will not restore already damaged lung and pancreatic tissue, it could beneficially impact the lives of thousands of younger patients, preventing worsening damage.

Serious side effects in the 510 people who participated in the clinical trials were high liver enzymes and a risk of cataracts. Other common adverse drug reactions were upper respiratory tract infections, influenza, rashes, gastrointestinal dysfunction and headaches. Certain antibiotics and seizure medicines can have negative interactions with Trikafta, and patients on those drugs should not take the new medication.

But the most serious downside for some patients is likely the cost of Trikafta — approximately $311,000 annually. According to the CFF, some insurance plans do not yet cover the drugs. Countries like France and the United Kingdom have recoiled at the cost, and the Institute for Clinical and Economic Review (ICER), a U.S. nonprofit that studies drug costs, concluded in 2018 that cystic fibrosis modulators were overpriced.

“Our analysis suggested that discounts of up to 77% would be needed to bring the prices into alignment with their clinical value to patients,” says Dan Ollendorf, PhD, ICER’s Chief Scientific Officer, in a press release at the time. A 2020 cost-benefit analysis of Trikafta has been postponed until later in 2020 due to COVID-19.