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Positive Phase 3 Study for Tezacaftor/Ivacaftor Combination in Children Aged 6-11 Years with Cystic Fibrosis Supports European Medicines Agency Submission
-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
“These data mark an important milestone in our efforts to expand
treatment options for patients living with CF,” said
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
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.
U.S. INDICATION AND IMPORTANT SAFETY INFORMATION FOR SYMDEKO® (tezacaftor/ivacaftor and ivacaftor) tablets
SYMDEKO is a prescription medicine used for the treatment of cystic fibrosis (CF) in patients aged 12 years and older who have two copies of the F508del mutation, or who have at least one mutation in the CF gene that is responsive to treatment with SYMDEKO. Patients should talk to their doctor to learn if they have an indicated CF gene mutation. It is not known if SYMDEKO is safe and effective in children under 12 years of age.
Patients should not take SYMDEKO if they take certain medicines or herbal supplements such as: the antibiotics rifampin or rifabutin; seizure medicines such as phenobarbital, carbamazepine, or phenytoin; St. John’swort.
Before taking SYMDEKO, patients should tell their doctor if they: have or have had liver problems; have kidney problems; are pregnant or plan to become pregnant because it is not known if SYMDEKO will harm an unborn baby; are breastfeeding or planning to breastfeed because it is not known if SYMDEKO passes into breast milk.
SYMDEKO may affect the way other medicines work, and other medicines may affect how SYMDEKO works. Therefore, the dose of SYMDEKO may need to be adjusted when taken with certain medicines. Patients should especially tell their doctor if they take antifungal medicines such as ketoconazole, itraconazole, posaconazole, voriconazole, or fluconazole; or antibiotics such as telithromycin, clarithromycin, or erythromycin.
SYMDEKO may cause dizziness in some people who take it. Patients should not drive a car, use machinery, or do anything that requires alertness until they know how SYMDEKO affects them.
Patients should avoid food or drink that contains grapefruit or
SYMDEKO can cause serious side effects, including:
High liver enzymes in the blood, which have been reported in people treated with SYMDEKO or treated with ivacaftor alone. The patient’s doctor will do blood tests to check their liver before they start SYMDEKO, every 3 months during the first year of taking SYMDEKO, and every year while taking SYMDEKO. Patients should call their doctor right away if they have any of the following symptoms of liver problems: pain or discomfort in the upper right stomach (abdominal) area; yellowing of the skin or the white part of the eyes; loss of appetite; nausea or vomiting; dark, amber-colored urine.
Abnormality of the eye lens (cataract) in some children and adolescents treated with SYMDEKO or with ivacaftor alone. If the patient is a child or adolescent, their doctor should perform eye examinations before and during treatment with SYMDEKO to look for cataracts.
The most common side effects of SYMDEKO include headache, nausea, sinus congestion, and dizziness.
These are not all the possible side effects of SYMDEKO. Please click here to see the fullU.S.Prescribing Information for SYMDEKO (tezacaftor/ivacaftor and ivacaftor) tablets.
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
Collaborative History with
Vertex initiated its CF research program in 2000 as part of a
collaboration with CFFT, the nonprofit drug discovery and development
affiliate of the
Special Note Regarding Forward-looking Statements
This press release contains forward-looking statements as defined in the
Private Securities Litigation Reform Act of 1995, including, without
limitation, the statements in the first paragraph of the press release
and quote by Dr. Kewalramani in the second paragraph. While Vertex
believes the forward-looking statements contained in this press release
are accurate, these forward-looking statements represent the company's
beliefs only as of the date of this press release and there are a number
of factors that could cause actual events or results to differ
materially from those indicated by such forward-looking statements.
Those risks and uncertainties include, among other things, that data
from the company's development programs may not support registration or
further development of its compounds due to safety, efficacy or other
reasons, and other risks listed under Risk Factors in Vertex's annual
report and quarterly reports filed with the
Vertex Pharmaceuticals Incorporated
Michael Partridge, 617-341-6108
Eric Rojas, 617-961-7205
Zach Barber, 617-341-6470
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