FDA decision on vanza triple, new CFTR modulator, due by Jan. 2

Vertex triple-combo therapy for CF under approval review in Europe, US

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Authorities in the U.S. and Europe are reviewing applications from Vertex Pharmaceuticals seeking approval of the company’s novel CFTR modulator triple combination, vanzacaftor, tezacaftor and deutivacaftor. 

Vertex is asking that the vanza combo be approved for people with cystic fibrosis (CF) ages 6 and older who carry at least one copy of F508del, the most common CF-causing mutation, or another mutation that’s responsive to the therapy.

In the U.S., the company used a priority review voucher to shorten the review time from 10 to six months, and a U.S. Food and Drug Administration (FDA) decision is expected by Jan. 2, 2025.

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Vertex didn’t specify when a decision on the vanza triple is expected in Europe. The company noted it also has applied for the new combination’s approval in Canada, Australia, Switzerland, and the U.K.

“The FDA acceptance of our vanza triple application and the MAA [marketing authorization application] validation by the EMA [European Medicines Agency] represent important milestones in the decades-long development of CFTR modulators and another example of our track record of serial innovation in CF,” Nia Tatsis, PhD, executive vice president, chief regulatory and quality officer at Vertex, said in a company press release.

CF is caused by mutations in the gene that provides instructions to make CFTR, a protein that helps to regulate the movement of water and salt molecules in and out of cells. CFTR dysfunction results in the production of abnormally thick and sticky mucus, which builds in organs and drives most symptoms of CF.

CFTR modulators are a class of medications that can boost the functionality of the defective CFTR protein in people with CF caused by specific mutations.

Vertex is developing the vanza triple combination as a next-generation successor to Trikafta (elexacaftor/tezacaftor/ivacaftor), a triple combination CFTR modulator therapy that’s widely approved for patients with F508del and other eligible mutations. The vanza triple contains tezacaftor, one of the same modulators used in Trikafta, alongside two novel modulators called vanzacaftor (VX-121) and deutivacaftor (VX-561).

Earlier this year, Vertex announced results from three Phase 3 clinical trials that tested the new combination against Trikafta in patients with responsive mutations. These are the SKYLINE 103 (NCT05076149) and SKYLINE 102 (NCT05033080) studies, which together evaluated the treatment in more than 1,000 adults and adolescents ages 12 and older, while the third study (NCT05422222) — due to conclude in June 2030 — has been testing it in children ages 1 through 11. 

Results showed patients generally had stable lung function with both Trikafta and the new therapy, but the new therapy was better than Trikafta at reducing levels of chloride ions (a type of salt molecule) in sweat. CFTR dysfunction leads to excessive sweat chloride levels, so the greater reduction in these levels implies that the new therapy better improves the defective protein’s ability to work.

Trial findings indicate that the vanza combination “raises the high bar set by Trikafta and gives more people with CF the chance to get to levels of sweat chloride below the diagnostic threshold for CF, and even to levels of sweat chloride seen in those without CF,” Tatsis said.