You are here
News & Events
Vertex Submits Supplemental New Drug Application (sNDA) to U.S. Food and Drug Administration for KALYDECO™ (ivacaftor) Monotherapy for People with Non-G551D Gating Mutations
-sNDA also includes long-term safety and efficacy data for KALYDECO from PERSIST open-label rollover study-
-Marketing Authorization Application (MAA) variation in Europe
"Today's submission to the
The sNDA submission is based on previously announced data from a Phase 3 study of ivacaftor monotherapy that showed statistically significant improvements in lung function (FEV1). The mean absolute treatment difference in percent predicted FEV1 between treatment with ivacaftor and placebo was 10.7% (p < 0.0001) and the mean relative treatment difference in percent predicted FEV1 was 14.2% (p < 0.0001) through the 8-week treatment period. The safety and tolerability results observed in this study were consistent with those observed in prior Phase 3 studies of ivacaftor monotherapy in people with CF who have the G551D mutation. The study in gating mutations is one of three ongoing Phase 3 label-expansion studies designed to evaluate whether additional people with CF may benefit from treatment with ivacaftor alone.
In addition to the sNDA submission, Vertex intends to submit a Marketing
Authorization Application (MAA) variation in Europe in
As part of the sNDA package, Vertex also submitted long-term data from the 96-week PERSIST open-label study of KALYDECO. PERSIST is an ongoing rollover study of people with cystic fibrosis ages 6 and older with a G551D mutation who took part in the 48-week Phase 3 STRIVE and ENVISON studies of KALYDECO. The data from PERSIST submitted as part of the sNDA included efficacy and safety results through 144 weeks of continuous treatment with KALYDECO.
The non-G551D gating data and the long-term PERSIST data will be presented at the 27th Annual North American Cystic Fibrosis Conference (NACFC) in Salt Lake City, Utah, October 17-19, 2013. Vertex expects the gating data to be presented as an oral presentation during Symposium III, "CFTR: Matching CFTR Mutations and Drugs," on October 19.
KALYDECO™ (ivacaftor) is the first medicine to treat the underlying
cause of CF in people with the G551D mutation 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
Vertex retains worldwide rights to develop and commercialize KALYDECO.
INDICATION AND IMPORTANT SAFETY INFORMATION FOR KALYDECO™ (ivacaftor)
Ivacaftor (150mg 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 for use in people with CF due to other mutations in the CFTR gene. It is not effective in patients with CF with 2 copies of the F508del mutation (F508del/F508del) in the CFTR gene. The efficacy and safety of ivacaftor in children younger than 6 years of age have not been evaluated.
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 which may diminish effectiveness. Therefore, co-administration is not recommended.
The dose of ivacaftor must be adjusted when used concomitantly with potent and moderate CYP3A inhibitors. The dose of ivacaftor must be adjusted 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 full U.S. Prescribing Information for KALYDECO at www.KALYDECO.com, the EU Summary of Product Characteristics for KALYDECO at http://goo.gl/N3Tz4, the Canadian Product Monograph for KALYDECO at www.vrtx.ca and the Australian Consumer Medical Information and Product Information for KALYDECO at http://bit.ly/18wlMld.
About Cystic Fibrosis
Cystic fibrosis is a rare, life-threatening genetic disease affecting
approximately 70,000 people worldwide, including 30,000 people in
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 1,800 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 absence of working CFTR protein 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
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 creates new possibilities in medicine. Our team discovers, develops and commercializes innovative therapies so people with serious diseases can lead better lives.
Vertex scientists and our collaborators are working on new medicines to cure or significantly advance the treatment of hepatitis C, cystic fibrosis, rheumatoid arthritis and other life-threatening diseases.
Founded more than 20 years ago 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, Dr. Kauffman's statements in the second paragraph of this
press release and statements regarding (i) Vertex's plan to submit a
Marketing Authorization Application (MAA) variation in
News Provided by Acquire Media