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Vertex Receives European CHMP Positive Opinion for KALYDECO™ (ivacaftor) in Eight Non-G551D Gating Mutations
-In Europe, approximately 250 people ages 6 and older have one of 8 additional gating mutations-
-KALYDECO is the first medicine to treat the underlying cause of CF in people with non-G551D gating mutations-
"People with these additional gating mutations generally have severe
cystic fibrosis, similar to patients with the most common gating
mutation, G551D. There is an urgent need for new medicines that address
the underlying cause of the disease for people with these mutations,"
Cystic fibrosis is caused by a defective or missing CFTR protein that results from mutations in the CFTR gene. CFTR proteins act as channels at the cell surface that control the flow of salt and water into and out of the cell. In people with gating mutations, the CFTR protein at the cell surface is defective and does not work properly, causing abnormally thick, sticky mucus to build up in the lungs. The digestive tract and a number of other organs are also affected. KALYDECO, an oral medicine known as a CFTR potentiator, helps the CFTR protein function more normally once it reaches the cell surface. KALYDECO targets the abnormal CFTR protein channels and opens them to allow chloride ions to move into and out of the cell, which helps thin the mucus so it can hydrate and protect the airways.
Today's CHMP opinion is based on previously announced data from the
first part of a Phase 3, two-part, randomised, double-blind,
placebo-controlled, cross-over study of 39 people with CF ages 6 and
older who have a non-G551D gating mutation. The first part of the study
showed statistically significant improvements in lung function (FEV1),
sweat chloride, BMI and CFQ-R scores. Data from the second part of the
study were presented at the
The CHMP's positive opinion will now be reviewed by the
The CHMP also issued a positive opinion recommending the inclusion of data from the long-term follow-up PERSIST study in the KALYDECO label. PERSIST is a Phase 3, open-label, 96-week, rollover extension trial that evaluated the long-term safety and durability of treatment with KALYDECO by enrolling people ages 6 and older with at least one copy of the G551D mutation who completed 48 weeks of treatment in the Phase 3 ENVISION and STRIVE studies (placebo and KALYDECO treatment groups) and met other eligibility criteria. Results from PERSIST demonstrated that the safety and efficacy of KALYDECO seen in the Phase 3 STRIVE and ENVISION trials was maintained through nearly three years (144 weeks) in G551D patients.
About KALYDECOTM (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 that aims to help
the CFTR protein function more normally once it reaches the cell
surface, to help hydrate and clear mucus from the airways. KALYDECO
(150mg, q12h) was first approved by the
KALYDECO was approved by the
Vertex retains worldwide rights to develop and commercialize KALYDECO.
INDICATION AND IMPORTANT SAFETY INFORMATION FOR KALYDECO™ (ivacaftor)
Ivacaftor (150 mg tablets) is indicated for the treatment of cystic fibrosis (CF) in patients age 6 years and older who have a G551D mutation in the CFTR gene.
Ivacaftor is not effective in patients with CF with 2 copies of the F508del mutation (F508del/F508del) in the CFTR gene. The safety and efficacy of ivacaftor in children with CF younger than 6 years of age have not been established.
Elevated liver enzymes (transaminases; ALT and AST) have been reported in patients receiving ivacaftor. It is recommended that ALT and AST be assessed prior to initiating ivacaftor, every 3 months during the first year of treatment, and annually thereafter. Patients who develop increased transaminase levels should be closely monitored until the abnormalities resolve. Dosing should be interrupted in patients with ALT or AST of greater than 5 times the upper limit of normal. Following resolution of transaminase elevations, consider the benefits and risks of resuming ivacaftor dosing.
Use of ivacaftor with medicines that are strong CYP3A inducers, such as the antibiotics rifampin and rifabutin; seizure medications (phenobarbital, carbamazepine, or phenytoin); and the herbal supplement St. John's Wort, substantially decreases exposure of ivacaftor and may diminish effectiveness. Therefore, co-administration is not recommended.
The dose of ivacaftor must be adjusted when used concomitantly with strong and moderate CYP3A inhibitors or when used in patients with moderate or severe hepatic disease.
Ivacaftor can cause serious adverse reactions including abdominal pain and high liver enzymes in the blood. The most common side effects associated with ivacaftor include headache; upper respiratory tract infection (the common cold), including sore throat, nasal or sinus congestion, and runny nose; stomach (abdominal) pain; diarrhea; rash; and dizziness. These are not all the possible side effects of ivacaftor. A list of the adverse reactions can be found in the product labeling for each country where ivacaftor is approved. Patients should tell their healthcare providers about any side effect that bothers them or does not go away.
Please see KALYDECO U.S. Prescribing Information, EU Summary of Product Characteristics, Canadian Product Monograph, Australian Consumer Medicine Information and Product Information, Swiss Prescribing Information and Patient Information, and the New Zealand Datasheet and Consumer Medicine Information.
About Cystic Fibrosis
Cystic fibrosis is a rare, life-shortening genetic disease affecting approximately 75,000 people in North America, Europe and Australia. Today, the median predicted age of survival for a person with CF is between 34 and 47 years, but the median age of death remains in the mid-20s.
CF is caused by a defective or missing 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 more than 1,900 known mutations in the CFTR gene. Some of these mutations, which can be determined by a genetic, or genotyping test, lead to CF by creating non-working or too few CFTR protein at the cell surface. The defective function or absence of CFTR proteins in people with CF results in poor flow of salt and water into and out of the cell in a number of organs, including the lungs. This leads to the buildup of abnormally thick, sticky mucus that can cause chronic lung infections and progressive lung damage.
Collaborative History with Cystic Fibrosis Foundation Therapeutics, Inc. (CFFT)
Vertex initiated its CF research program in 1998 as part of a
collaboration with CFFT, the nonprofit drug discovery and development
affiliate of the
Vertex is a global biotechnology company that aims to discover, develop and commercialize innovative medicines so people with serious diseases can lead better lives. In addition to our clinical development programs focused on cystic fibrosis, Vertex has more than a dozen ongoing research programs aimed at other serious and life-threatening diseases.
Founded in 1989 in
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, statements regarding the
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