-Mean absolute treatment difference in lung function (percent predicted FEV1) between treatment with ivacaftor and placebo was 10.7% (p < 0.0001); mean relative treatment difference between treatment with ivacaftor and placebo was 14.2% (p < 0.0001)-
-Statistically significant improvements in weight gain and in patient-reported quality of life as measured by the respiratory domain of the Cystic Fibrosis Questionnaire Revised (CFQ-R)-
-Supplemental New Drug Application (sNDA) in
Based on these data, Vertex plans to submit a supplemental New Drug
Application (sNDA) in
"Our goal in CF is to help as many people as possible with our
medicines, and these data are an important step toward that goal," said
About the Study
The Phase 3 crossover study of ivacaftor enrolled 39 people with CF ages 6 and older who have at least one non-G551D gating mutation. Patients received either ivacaftor, or placebo, for eight weeks, followed by a 4-week washout period. Following the washout period, patients who received placebo in the first eight weeks received ivacaftor for weeks 12 to 20, and patients who received ivacaftor for the first eight weeks received placebo for weeks 12 to 20. The primary analysis was conducted at week 20 of the study, and the primary endpoint of the study was absolute change from baseline in percent predicted FEV1. Following the end of the crossover periods, all patients receive ivacaftor from week 20 to week 36 as part of an open-label dosing period.
In this study, 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 study met its primary endpoint. The mean absolute and relative percent predicted FEV1 improvements during ivacaftor treatment (within-group) were 7.5% (p < 0.0001) and 10.8% (p < 0.0001), respectively. Additionally, treatment with ivacaftor in this study resulted in statistically significant improvements in weight gain and in improvements in patient-reported quality of life as measured by the respiratory domain of the Cystic Fibrosis Questionnaire Revised (CFQ-R). Full data from this study will be submitted for presentation at a medical meeting in the second half of 2013.
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 most commonly observed adverse events, regardless of treatment assignment, included pulmonary exacerbation, cough, headache and abdominal pain, each occurring more frequently while patients received placebo than when patients received ivacaftor.
Two additional Phase 3 label-expansion studies are ongoing for ivacaftor monotherapy, including a study in people with CF ages 6 and older who have at least one copy of the R117H mutation and a study in children with CF ages 2 to 5 who have a gating mutation, including the G551D mutation. A Phase 2 proof-of-concept study evaluating ivacaftor in people with CF who have clinical evidence of residual CFTR function is also ongoing.
Indication and Important Safety Information for KALYDECOTM (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 CF patients with two 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.
High 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. Moderate transaminase elevations are common in subjects with CF. Overall, the incidence and clinical features of transaminase elevations in clinical trials was similar between subjects in the ivacaftor and placebo treatment groups. In the subset of patients with a medical history of elevated transaminases, increased ALT or AST have been reported more frequently in patients receiving ivacaftor compared to placebo.
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 concomitantly used 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 full product labeling for each country where ivacaftor is approved. Patients should tell their healthcare providers about any side effect that bothers them or doesn't 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, and the KALYDECO Canadian Product Monograph at www.vrtx.ca.
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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 third paragraph of this
press release and statements regarding (i) Vertex's plan to submit an
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