Vertex’s Orkambi Safe and Effective for Treating CF F508del Mutation

Two Phase III clinical trials from Northwestern University’s Feinberg School of Medicine and Stanley Manne Children’s Research Institute at Ann Robert H. Lurie Children’s Hospital of Chicago tested a combination treatment plan in patients with cystic fibrosis. The results show that lumacaftor/ivacaftor, to be marketed under the brand name Orkambi by Vertex, is safe for patients homozygous for F508del — the most common genetic mutation in cystic fibrosis — and lowers the rate of pulmonary exacerbations.

“These groundbreaking findings will benefit around 15,000 patients in US alone,” said Susanna McColley, MD, in a news release from Lurie Children’s. Dr. McColley is Director of the Clinical and Translational Research Program at Lurie Children’s and was a contributing author on the study, “Lumacaftor–Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del CFTR,” which was published in The New England Journal of Medicine.

The trials evaluated the combination of ivacaftor and lumacaftor in 1,108 patients aged 12 years and older at multiple centers in the United States. Patients were treated for a total of 24 weeks. “We will need more analyses and longer-term data to see if this treatment can alter the disease course and further extend the life expectancy of our patients,” noted Dr. McColley.

Two treatment doses were tested: 250 mg of ivacaftor with either 600 mg daily of lumacaftor or 400 mg twice daily of lumacaftor. Both treatment groups were effective in lessening the symptoms of cystic fibrosis. Treated patients saw a 2.6% to 4.0% improvement in forced expiratory volume in one-second (FEV1), which corresponded to a 4.3% to 6.7% improvement over patients given placebo. Combination treatment also reduced the rate of pulmonary exacerbations by 30% to 39% relative to the placebo group.

“While significant progress has been made with supportive therapies for cystic fibrosis, developing treatments that address the underlying genetic cause has been a challenge,” said Dr. McColley. “Just a few years ago, ivacaftor became the only FDA-approved drug for the genetic defect in cystic fibrosis, but it only works for genetic mutations found in a small portion of cystic fibrosis patients. Our study showed that combining ivacaftor with lumacaftor helps patients with the most common cystic fibrosis mutation. This is an exciting step forward.”

The news comes after the FDA Pulmonary-Allergy Drugs Advisory Committee met last week to discuss the results of this Phase III study, among others demonstrating the efficacy of lumacaftor/ivacaftor treatment. Following the receipt of a positive recommendation, lumacaftor with ivacaftor is now pending approval by the FDA to treat patients homozygous for F508del.