Data From Follow-Up Study of KALYDECO(TM) (ivacaftor) Showed Durable Improvements in Lung Function and Other Measures of Disease in People with Cystic Fibrosis Who Have a Specific Genetic Mutation (G551D)
- Data from nine presentations at the European Cystic Fibrosis Society Conference underscore Vertex's ongoing commitment to change CF treatment by targeting the underlying cause of the disease -
DUBLIN--(BUSINESS WIRE)-- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) announced today new data from a long-term follow-up study that showed that the improvements in lung function (forced expiratory volume in one second, FEV1), respiratory symptoms and weight gain among people who were treated with KALYDECO™ (ivacaftor) for 48 weeks in one of two pivotal studies (STRIVE or ENVISION) were durable for up to 96 total weeks of treatment. The ongoing PERSIST extension study enrolled people with cystic fibrosis (CF) ages 6 and older who have at least one copy of the G551D mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and who completed treatment in the Phase 3 STRIVE or ENVISION studies (KALYDECO and placebo treatment groups) and met certain other eligibility criteria. A total of nine presentations on KALYDECO are being presented at the 35th European Cystic Fibrosis Society (ECFS) Conference in Dublin, June 6 to 9, 2012.
"KALYDECO has fundamentally changed the way we approach the development of new medicines for cystic fibrosis by targeting the underlying cause of the disease," said Chris Wright, M.D., Ph.D., Senior Vice President of Global Medicines Development and Affairs at Vertex. "We are working hard to understand which additional patients may be helped by KALYDECO and simultaneously exploring potential new medicines that may be able to help many more people with CF."
KALYDECO is the first medicine to treat the underlying cause of CF, a rare, genetic disease caused by defective or missing CFTR proteins resulting from mutations in the CFTR gene. In people with the G551D mutation, KALYDECO helps the defective CFTR protein function more normally. An estimated 1,200 people in the United States and 1,100 people in Europe with CF have at least one copy of the G551D mutation. KALYDECO was approved by the U.S. Food and Drug Administration (FDA) in January 2012 for use in people with CF ages 6 and older who have at least one copy of the G551D mutation in the CFTR gene. Vertex recently received a positive opinion from the European Committee for Medicinal Products for Human Use (CHMP) recommending the approval of KALYDECO.
KALYDECO benefits and safety sustained for up to 96 weeks (ECFS Abstract WS6.4, Thursday @ 15:56 GMT)
At the time of this analysis, 74 adults and adolescents (ages 12 or older) who were first treated with KALYDECO in the STRIVE study are continuing treatment in PERSIST and have completed a total of 96 weeks of treatment with KALYDECO. A 9.5 percentage-point mean absolute improvement from the STRIVE baseline in lung function (percent predicted FEV1) was observed at week 96. Twenty-five children (ages 6 to 11) who were first treated with KALYDECO in the ENVISION study are continuing treatment in PERSIST and have completed a total of 72 weeks of treatment with KALYDECO. A 10.1 percentage-point mean absolute improvement from the ENVISION baseline in lung function was observed at week 72.
In addition, the analysis presented this week showed that people who switched to KALYDECO after receiving 48 weeks of treatment with placebo in the Phase 3 studies (n=86), experienced improvements in lung function, respiratory symptoms and weight gain comparable to those seen in people who received KALYDECO from the beginning of the Phase 3 studies.
Adverse events seen to date in people receiving KALYDECO in the PERSIST study were generally consistent with those seen with KALYDECO treatment during the original Phase 3 studies. The majority of adverse events associated with KALYDECO were mild or moderate in severity and resolved during the reporting period. No new adverse events were identified. The most common adverse events reported in PERSIST were predominantly respiratory-related and included pulmonary exacerbations, cough, productive cough and upper respiratory tract infection. The most commonly reported serious adverse events (that occurred in more than one patient) in PERSIST were pulmonary exacerbations, hemoptysis and intestinal obstruction. At the time of this PERSIST analysis, approximately 1.0 percent of study participants had discontinued treatment due to an adverse event.
KALYDECO improved lung function in people with early-stage CF (ECFS Abstract WS7.6, Thursday @18:00 GMT)
CF-related lung disease is known to start before it's detectable by deterioration in FEV1. Once FEV1 has fallen below normal, (80 percent to 85 percent predicted), structural damage may have already occurred; much of this can be irreversible.
Data from a Phase 2 randomized, double-blind, crossover study of people with early-stage CF (FEV1 greater than 90 percent predicted) ages 6 and older who have at least one copy of the G551D mutation, were presented at the conference and showed that KALYDECO led to statistically significant improvements in lung function. At baseline, the mean percent predicted FEV1 for study participants (n=20) was 97.2 percent. Through 29 days of treatment, the mean absolute improvement in lung function was 8.7 percentage points compared to placebo (p=0.0103).
"Cystic fibrosis is a progressive disease and as patients get older, lung damage progresses and often becomes irreversible," said KALYDECO investigator Jane Davies, M.D., Royal Brompton Hospital and Imperial College, London. "The goal of this study was to start to help us understand whether patients might benefit from treatment with KALYDECO before they show severe signs and symptoms of CF. The initial findings are encouraging and support longer-term studies and evaluation."
KALYDECO significantly reduced risk of pulmonary exacerbations (ECFS Poster #44)
An analysis of data from the Phase 3 STRIVE study that enrolled people ages 12 and older with at least one copy of the G551D mutation was presented at the conference. As previously reported, people treated with KALYDECO were 55 percent less likely to experience a pulmonary exacerbation compared to those treated with placebo through week 48. Pulmonary exacerbations are generally considered periods of worsening in the signs and symptoms of CF that often require treatment with antibiotics and hospital visits. New data were obtained from statistical modeling and showed that patients treated with KALYDECO were also significantly less likely than those treated with placebo to require hospitalization and intravenous antibiotics. Through 48 weeks, people treated with KALYDECO, compared to those treated with placebo, were 67 percent less likely to require hospitalization for a pulmonary exacerbation and 59 percent less likely to require intravenous antibiotics for a pulmonary exacerbation.
Vertex continues to pursue goal of treating more people with CF
Vertex is committed to developing new medicines to treat the underlying cause of CF. The company plans to begin three additional pivotal studies in 2012 to explore the safety and efficacy of KALYDECO; a study of people with the R117H CFTR mutation, a study of people with CFTR gating mutations that were not evaluated in the previous Phase 3 studies, and a study of children with CF as young as 2 years old who have gating mutations. Vertex is also conducting two Phase 2 studies of KALYDECO in combination with a CFTR corrector, VX-809 or VX-661, to treat people with the most common form of CF.
KALYDECO, VX-809 and VX-661 were discovered as part of a collaboration with Cystic Fibrosis Foundation Therapeutics, Inc., the nonprofit drug discovery and development affiliate of the Cystic Fibrosis Foundation. |
