FDA expands Trikafta approval for 94 more CFTR gene mutations
New approval means about 300 more CF patients are eligible for treatment
The U.S. Food and Drug Administration (FDA) has expanded the approval of Trikafta for people with cystic fibrosis (CF) ages 2 and older who carry certain mutations that are responsive to the medication.
With the approval, 94 additional non-F508del CFTR mutations have been added to the medication’s label, meaning about 300 more CF patients in the U.S. are now eligible for the treatment, according to Vertex Pharmaceuticals.
“With this approval, even more patients may be able to benefit from a medicine that treats the underlying cause of their disease,” Carmen Bozic, MD, executive vice president of global medicines development and medical affairs and chief medical officer at Vertex, said in a company press release. “We look forward to continuing the work to extend the approvals and availability of our medicines to patients around the world.”
The therapy is now available to CF patients who carry one F508del mutation or a non-F508del mutation in the CFTR gene that’s responsive based on clinical and/or lab test data. If a patient’s mutation is unknown, an FDA-cleared CF mutation test can confirm at least one indicated mutation.
In addition, safety information on liver failure and liver injury, which has been reported in some patients within the first 15 months of treatment, has been updated from warnings and precautions to a boxed warning. All patients must have liver function tests before starting Trikafta, every month during the first six months of treatment, every three months for the next 12 months, and at least annually thereafter. More frequent monitoring may be needed for those with a history of liver disease or liver function test elevations before treatment.
Trikafta treatment should be interrupted if significant elevations in lung function tests or signs or symptoms of liver injury occur. Treatment can be resumed if the abnormalities resolve and its benefit is expected to outweigh the risk. The therapy shouldn’t be used in people with severe liver impairment and isn’t recommended in those with moderate hepatic impairment.
A ‘transformative impact’
Certain mutations in the CFTR gene cause CF, which leads to a faulty or missing CFTR protein. A lack of the protein’s functionality impairs the flow of salt and water into and out of the cells in various organs. In the lungs, this results in the buildup of abnormally thick, sticky mucus, chronic lung infections, and progressive lung damage.
While more than 2,000 CFTR mutations have been identified, around 90% of people with CF have at least one F508del mutation.
Trikafta is a CFTR modulator that helps the faulty CFTR protein work more effectively. Two of its three active ingredients — elexacaftor and tezacaftor — help the protein fold correctly and bring more protein to the cell surface. The third ingredient is ivacaftor, also sold independently as Kalydeco, which is known as a potentiator because it binds to the CFTR protein and holds the channel open so more salt can pass through.
The FDA first approved Trikafta in 2019 to treat CF patients ages 12 and older with at least one F508del mutation. In 2020, the agency expanded the number of eligible mutations, then expanded it again in 2021 to include children as young as 6. The therapy last year became available to children as young as 2.
“Since its first approval in 2019, Trikafta has had a transformative impact on tens of thousands of people living with cystic fibrosis,” Bozic said.
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