“We believe it is important to treat the underlying cause of cystic fibrosis as early as possible, and are pleased that parents and physicians now have a medicine to treat the underlying cause of CF in indicated patients as young as one year of age,” said Reshma Kewalramani, M.D., Executive Vice President and Chief Medical Officer at Vertex. “We look forward to working with the Canadian health officials and provinces to achieve rapid access to KALYDECO for this small, but important group of young children.”
The label update is based on data from the ongoing Phase 3 open-label safety study (ARRIVAL) of children with CF aged 12 to <24 months who have a gating mutation in the CFTR gene. The study demonstrated a safety profile consistent with that observed in previous Phase 3 studies of older children and adults, and improvements in sweat chloride, a key secondary efficacy endpoint.
KALYDECO was previously approved for expanded use in patients aged 12 to <24 months by the U.S. Food and Drug Administration (FDA) in August of 2018 and by the European Commission in November of the same year.
About Cystic Fibrosis
Cystic fibrosis is a rare, life-threatening genetic disease affecting approximately 75,000 people in North America, Europe and Australia, including 4,200 people in Canada.
CF is caused by a defective or missing cystic fibrosis transmembrane conductance regulator (CFTR) 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.
About the ARRIVAL Study
The ARRIVAL study is an ongoing Phase 3 open-label safety study of 25 children with CF aged 12 to <24 months who have one of 10 mutations in the CFTR gene (G551D, G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P, G1349D or R117H). The study demonstrated a safety profile consistent with that observed in previous Phase 3 studies of older children and adults; most adverse events were mild or moderate in severity, and no patient discontinued due to adverse events.
Two patients had elevated liver enzymes greater than eight times the upper limit of normal, but continued to receive KALYDECO after a dose interruption. The most common adverse events (≥30%) were cough (74%), pyrexia (37%), elevated aspartate aminotransferase (37%), elevated alanine aminotransferase (32%) and runny nose (32%). Four serious adverse events were observed in two patients.
Mean baseline sweat chloride for the children in this study was 104.1 mmol/L (n=14). Following 24 weeks of treatment with KALYDECO, the mean sweat chloride level was 33.8 mmol/L (n=14). In the 10 subjects with paired sweat chloride samples at baseline and week 24, there was a mean absolute change of -73.5 mmol/L. These data were presented at the 41st European Cystic Fibrosis Society (ECFS) Conference in June 2018 and published in The Lancet Respiratory Medicine (Volume 6, No 7, July 2018).
About KALYDECO (ivacaftor)
KALYDECO (ivacaftor) is the first medicine to treat the underlying cause of CF in people with specific mutations in the CFTR gene. Known as a CFTR potentiator, KALYDECO is an oral medicine designed to keep CFTR proteins at the cell surface open longer to improve the transport of salt and water across the cell membrane, which helps hydrate and clear mucus from the airways. KALYDECO is available as 150 mg tablets for adults and pediatric patients age 6 years and older, and is taken with fat-containing food. It is also available as 50 mg and 75 mg granules in pediatric ages 12 months to less than 6 years and is administered with soft-food or liquid with fat-containing food.
People with CF who have specific mutations in the CFTR gene are currently benefiting from KALYDECO in 27 different countries across North America, Europe and Australia.
Source: Company Press Release