The U.S. Food and Drug Administration (FDA) has granted priority review to Vertex’s new drug application for its triple combination — elexacaftor (VX-445) plus tezacaftor and Kalydeco (ivacaftor) — for cystic fibrosis (CF) patients who cannot use the company’s other disease-modifying treatments or don’t benefit as intended.
The FDA is expected to announce its final decision by March 19, 2020, according to the announced Prescription Drug User Fee Act (PDUFA) action date.
Now the agency will review the data Vertex has delivered to support the approval of the triple combo therapy, which includes positive results from two clinical trials in the Phase 3 AURORA program — AURORA F/MF and F/F trials — testing the triple combo therapy in patients with either one or two copies of the F508del mutation in the CFTR gene, the one defective in CF.
AURORA F/MF (NCT03525444) included 403 people with CF caused by one F508del and one minimal function mutation who were treated with either the triple combination or placebo for up to 24 weeks. In AURORA F/F (NCT03525548), 107 patients with two F508del mutations were treated with either elexacaftor or a placebo in combination with tezacaftor and Kalydeco for four weeks.
Data from both studies showed that patients given the triple combination therapy had significant improvements in lung function, as assessed by the percent predicted forced expiratory volume in one second (ppFEV1), which was the primary goal in both studies. The ppFEV1 increased by an average of 14.3% in the 24-week trial, and by 10% in the four-week trial.
In addition, patients who received the combo therapy showed improvements in all of the AURORA F/MF trial’s secondary goals, including a lower annual rate of pulmonary exacerbations and reduced levels of chloride in patients’ sweat. The treatment was generally well-tolerated in both studies.
“If approved, the VX-445 (elexacaftor), tezacaftor, and ivacaftor triple combination regimen would be a significant advance in CF treatment as the first CFTR modulator for those with one F508del mutation and one minimal function mutation, and bring additional benefit to patients with two F508del mutations,” Reshma Kewalramani, MD, executive vice president and chief medical officer at Vertex, said in a press release.
Both elexacaftor and tezacaftor work to increase the amount of CFTR functional protein at the cell surface by correcting the abnormal F508del mutated protein, while Kalydeco boosts the function of CFTR.
“Our goal is to provide medicines that treat the underlying cause of CF to the vast majority of people with CF,” Kewalramani said. “We share a sense of urgency with people with CF, caregivers and clinicians to rapidly deliver innovative CF medicines to those waiting, and we look forward to working with the agency as they review the application over the course of the coming months.”