-Study met primary endpoint with a statistically significant improvement in absolute change in lung clearance index (LCI2.5) through 8 weeks of tezacaftor/ivacaftor treatment-
-Tezacaftor in combination with ivacaftor was generally well tolerated and safety data were consistent with previous studies-
-Data support a submission to the European Medicines Agency in the second half of 2019-
BOSTON, MA, USA I February 14, 2019 I Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced 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 (CF) who have either two copies of the F508del mutation or one copy of the F508del mutation and one residual function mutation. 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 (EMA) 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 U.S. Food and Drug Administration (FDA) for tezacaftor/ivacaftor based on a previously completed Phase 3 safety study in children ages 6 through 11 years of age conducted in the U.S. and Canada.
“These data mark an important milestone in our efforts to expand treatment options for patients living with CF,” said Reshma Kewalramani, M.D., Executive Vice President and Chief Medical Officer at Vertex. “We plan to submit an indication extension to the EMA in the second half of 2019, bringing us a step closer to potentially providing more children with a treatment option that addresses the underlying cause of the disease.”
Summary of Key Data
The data announced today are from a Phase 3, randomized, 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 randomized 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 percent 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 (FEV1). 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.
About Cystic Fibrosis
Cystic Fibrosis (CF) 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 (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 SYMDEKO® (tezacaftor/ivacaftor and ivacaftor)
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.
About Vertex
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.
Founded in 1989 in Cambridge, Mass., Vertex’s headquarters is now located in Boston’sInnovation District. Today, the company has research and development sites and commercial offices in the United States, Europe, Canada, Australia and Latin America. Vertex is consistently recognized as one of the industry’s top places to work, including being named to Science magazine’s Top Employers in the life sciences ranking for nine years in a row. For additional information and the latest updates from the company, please visit www.vrtx.com.
Collaborative History with Cystic Fibrosis Foundation Therapeutics, Inc. (CFFT)
Vertex initiated its CF research program in 2000 as part of a collaboration with CFFT, the nonprofit drug discovery and development affiliate of the Cystic Fibrosis Foundation. KALYDECO® (ivacaftor), ORKAMBI®(lumacaftor/ivacaftor), SYMDEKO® (tezacaftor/ivacaftor and ivacaftor), VX-659 and VX-445 were discovered by Vertex as part of this collaboration.
SOURCE: Vertex Pharmaceuticals
Post Views: 29
-Study met primary endpoint with a statistically significant improvement in absolute change in lung clearance index (LCI2.5) through 8 weeks of tezacaftor/ivacaftor treatment-
-Tezacaftor in combination with ivacaftor was generally well tolerated and safety data were consistent with previous studies-
-Data support a submission to the European Medicines Agency in the second half of 2019-
BOSTON, MA, USA I February 14, 2019 I Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced 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 (CF) who have either two copies of the F508del mutation or one copy of the F508del mutation and one residual function mutation. 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 (EMA) 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 U.S. Food and Drug Administration (FDA) for tezacaftor/ivacaftor based on a previously completed Phase 3 safety study in children ages 6 through 11 years of age conducted in the U.S. and Canada.
“These data mark an important milestone in our efforts to expand treatment options for patients living with CF,” said Reshma Kewalramani, M.D., Executive Vice President and Chief Medical Officer at Vertex. “We plan to submit an indication extension to the EMA in the second half of 2019, bringing us a step closer to potentially providing more children with a treatment option that addresses the underlying cause of the disease.”
Summary of Key Data
The data announced today are from a Phase 3, randomized, 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 randomized 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 percent 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 (FEV1). 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.
About Cystic Fibrosis
Cystic Fibrosis (CF) 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 (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 SYMDEKO® (tezacaftor/ivacaftor and ivacaftor)
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.
About Vertex
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.
Founded in 1989 in Cambridge, Mass., Vertex’s headquarters is now located in Boston’sInnovation District. Today, the company has research and development sites and commercial offices in the United States, Europe, Canada, Australia and Latin America. Vertex is consistently recognized as one of the industry’s top places to work, including being named to Science magazine’s Top Employers in the life sciences ranking for nine years in a row. For additional information and the latest updates from the company, please visit www.vrtx.com.
Collaborative History with Cystic Fibrosis Foundation Therapeutics, Inc. (CFFT)
Vertex initiated its CF research program in 2000 as part of a collaboration with CFFT, the nonprofit drug discovery and development affiliate of the Cystic Fibrosis Foundation. KALYDECO® (ivacaftor), ORKAMBI®(lumacaftor/ivacaftor), SYMDEKO® (tezacaftor/ivacaftor and ivacaftor), VX-659 and VX-445 were discovered by Vertex as part of this collaboration.
SOURCE: Vertex Pharmaceuticals
Post Views: 29
