Lumacaftor: Phase II data

An 8-week, exploratory Phase II trial in 125 CF patients ages >=12 who have 1 copy of the delta F508 CFTR mutation showed that twice-daily 400 mg lumacaftor plus twice-daily 250 mg Kalydeco ivacaftor missed the primary endpoint of improving the mean absolute change in percent predicted FEV1 from baseline to week 56 vs. placebo (reduction of 0.62 vs. a reduction of 1.23 percentage points, p=0.5978). On secondary endpoints, lumacaftor plus Kalydeco led to a significant mean absolute improvement in CFQ-R score from baseline to day 56 of 6.48 points compared to placebo (p=0.0131). Additionally, lumacaftor plus Kalydeco significantly reduced sweat chloride levels from baseline to day 56 by 11.03 mmol/L vs. placebo (p<0.0001). There was no observed increase in BMI. Lumacaftor plus Kalydeco was generally well tolerated.

In June, Vertex reported data from the identical, double-blind, international Phase III TRAFFIC and TRANSPORT trials in CF patients who have 2 copies of the delta F508 CFTR mutation showing that lumacaftor plus Kalydeco met the primary endpoint in both trials (see BioCentury, June 30). In 4Q14, Vertex plans to submit an NDA to FDA and MAA to EMA for lumacaftor plus Kalydeco to treat CF in patients ages >=12 who have 2 copies of the delta F508 CFTR mutation. The combination has breakthrough therapy designation for the indication in the U.S. According to the company, there are more than 22,000 CF patients ages >=12 in North America, Europe and Australia who have 2 copies of the delta F508 CFTR mutation, which Vertex said is the most prevalent genetic mutation that causes the disease. ...