20 February 2019 - - US-based biotechnology company Vertex Pharmaceuticals Inc. (NASDAQ: VRTX) has received the results of a Phase 3 study conducted in Europe and Australia of tezacaftor in combination with ivacaftor in children aged 6 through 11 years with cystic fibrosis who have either two copies of the F508del mutation or one copy of the F508del mutation and one residual function mutation, the company said.

The study met its primary endpoint of absolute change in lung clearance index (LCI2.5) through 8 weeks of treatment, demonstrating a statistically significant improvement in LCI2.5 among patients treated with tezacaftor/ivacaftor. The regimen was generally well tolerated and safety data were consistent with those observed in previous studies with tezacaftor/ivacaftor.

This efficacy study was designed to support a submission to the European Medicines Agency to extend the indication of tezacaftor/ivacaftor in this patient population.

Vertex plans to submit the application in the second half of 2019. In late 2018, Vertex submitted an sNDA to the US Food and Drug Administration for tezacaftor/ivacaftor based on a previously completed Phase 3 safety study in children ages 6 through 11 years of age conducted in the US and Canada.

The data announced are from a Phase 3, randomised, double-blind, parallel-group study to evaluate the efficacy and safety of tezacaftor in combination with ivacaftor in children ages 6 through 11 who have either two copies of the F508del mutation or one copy of the F508del mutation and one residual function mutation.

Subjects were randomised 4: 1 based on their genotype to tezacaftor/ivacaftor versus a blinding arm (placebo for those with two copies of F508del; ivacaftor for those with one copy of F508del mutation and one residual function mutation). The study randomized and treated 54 subjects with TEZ/IVA, 10 with placebo, and 3 with ivacaftor.

The primary endpoint of the study was the within-group absolute change in lung clearance index (LCI2.5) from baseline through Week 8 in patients treated with tezacaftor/ivacaftor.

LCI2.5 measures the efficiency of ventilation in the lungs by quantifying how many standard lung volumes it takes to reduce exhaled nitrogen to 2.5% of its starting value when breathing pure oxygen.

LCI is considered a more sensitive measure to detect early lung disease than forced expiratory volume in one second. Higher LCI scores indicate poorer lung function.

To participate in the study, children at an initial screening visit had to have an LCI2.5 ≥7.5, which is considered the cutoff for abnormal gas exchange. In the study, 54 children that were treated with tezacaftor/ivacaftor experienced a mean within-group absolute improvement in LCI2.5 of -0.51 through 8 weeks (p < 0.0001).

Overall, safety data were similar to those observed in previous studies of tezacaftor/ivacaftor. The most common adverse events (≥ 10%) among those patients receiving tezacaftor/ivacaftor were cough, headache, and productive cough. No serious adverse events or adverse events leading to treatment discontinuation or interruption were observed.

Cystic Fibrosis is a rare, life-shortening genetic disease affecting approximately 75,000 people in North America, Europe and Australia.

CF is caused by a defective or missing cystic fibrosis transmembrane conductance regulator protein resulting from mutations in the CFTR gene. Children must inherit two defective CFTR genes -- one from each parent -- to have CF.

There are approximately 2,000 known mutations in the CFTR gene. Some of these mutations, which can be determined by a genetic test, or genotyping test, lead to CF by creating non-working or too few CFTR proteins at the cell surface. The defective function or absence of CFTR protein results in poor flow of salt and water into and out of the cell in a number of organs.

In the lungs, this leads to the buildup of abnormally thick, sticky mucus that can cause chronic lung infections and progressive lung damage in many patients that eventually leads to death. The median age of death is in the mid-to-late 20s.

Some mutations result in CFTR protein that is not processed or folded normally within the cell, and that generally does not reach the cell surface. SYMDEKO is a combination of tezacaftor and ivacaftor.

Tezacaftor is designed to address the trafficking and processing defect of the CFTR protein to enable it to reach the cell surface where ivacaftor can increase the amount of time the protein stays open.

Vertex is a global biotechnology company that invests in scientific innovation to create transformative medicines for people with serious and life-threatening diseases.

In addition to clinical development programs in CF, Vertex has more than a dozen ongoing research programs focused on the underlying mechanisms of other serious diseases.