Vertex Reveals Encouraging Long-Term Data on Disease Improvement for Orkambi CF Combo Therapy

Vertex Pharmaceuticals Incorporated recently announced in a press release new data on its long-term PROGRESS study testing the investigational regimen ORKAMBI (lumacaftor/ivacaftor) for cystic fibrosis (CF). The data was presented at the 38th European Cystic Fibrosis Society (ECFS) Conference, June 10-13, 2015 held in Brussels, Belgium in an oral presentation entitled “Lumacaftor in combination with ivacaftor in patients with cystic fibrosis who are homozygous for the F508del-CFTR mutation” (Abstract WS01.3, Workshop 1 – Strategies to correct CFTR defects).

CF is a rare, life-threatening genetic disease in which a defective gene (cystic fibrosis transmembrane conductance regulatory, CFTR) induces a salt imbalance, causing the body to form unusually thick, sticky mucus that can obstruct the airways and promote dangerous lung infections, resulting in serious respiratory and also gastrointestinal manifestations. The majority of the CF patients die due to respiratory failure. There is no cure for the disease and it is estimated that almost 75,000 individuals worldwide suffer from CF. In order to have the disease, children have to inherit two defective CFTR genes, one from each parent. There are more than 1,900 known mutations in the CFTR gene with the F508del mutation being present in approximately 85% of CF patients.

The 96-week PROGRESS Phase 3 trial enrolled 1,031 CF patients (aged 12 or older) with two copies of the F508del mutation and who have completed the 24 weeks lumacaftor/ivacaftor combination treatment in the placebo-controlled Phase 3 TRAFFIC or TRANSPORT trials. Both lumacaftor and ivacaftor drugs target the defective CFTR protein. An interim analysis was performed at 24 weeks into the PROGRESS trial.

The team found that the lung function improvement previously observed in the TRAFFIC and TRANSPORT studies after lumacaftor/ivacaftor combination treatment was sustained through the 48 weeks of treatment (24 weeks TRAFFIC/TRANSPORT plus 24 weeks PROGRESS) in all patients tested. In addition, researchers found that patients had a reduction in the rate of pulmonary exacerbations rate, and an improvement in their respiratory symptoms and body mass index (BMI). Interestingly, patients who received a placebo drug in the TRAFFIC or TRANSPORT studies and then a lumacaftor/ivacaftor regimen for 24 weeks in the PROGRESS study were found to have a similar response to patients under the lumacaftor/ivacaftor regimen already in the TRAFFIC/TRANSPORT plus the PROGRESS studies (in a total of 48 weeks of treatment). In terms of safety and tolerability, lumacaftor/ivacaftor regimen was found to be relatively well tolerated by the patients.

The PROGRESS study is still underway to determine the long-term effects of the lumacaftor/ivacaftor combination treatment in CF patients.