Rare Disease Report
Patients & Caregivers

Vertex Announces its Phase 3 Cystic Fibrosis Studies Met Their Primary Endpoint with Combination Therapy

JUNE 24, 2014
RDR Staff

Very exciting news for the cystic fibrosis community was announced today by Vertex Pharmaceuticals. Their two phase 3 studies examining the efficacy and safety of lumacaftor plus Kalydeco (ivacaftor) in people with cystic fibrosis (CF) who have two copies (homozygous) of the F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene met their primary endpoints (i.e., statistically significant improvements in lung function  as measured by percent predicted forced expiratory volume in one second, or ppFEV1).

Based in these results, the company plans to submit a New Drug Application (NDA) in the U.S. and Marketing Authorisation Application (MAA) in Europe in the fourth quarter of 2014. Anticipating the excitement this new data will create in the cystic fibrosis community, Vertex also announced it will explore options to make the combination of lumacaftor and ivacaftor available to certain patients who have two copies of the F508del mutation while they are seeking approval of this regimen from regulatory agencies around the world via a compassionate use program.

Cystic fibrosis is a rare life-shortening genetic disease that affects approximately 30,000 people in the United States and 70,000 people worldwide. The average age of death remains in the mid-20s. Cystic fibrosis is caused by a defective or missing CFTR protein resulting from mutations in the CFTR gene. The CFTR protein functions as a channel across the membrane of cells that produce mucus, sweat, saliva, tears, and digestive enzymes. More than 1,000 mutations in the CFTR gene have been identified in people with cystic fibrosis. The most common mutation is F508del.  
Disease-causing mutations in the CFTR gene alter the production, structure, or stability of the chloride channel. All of these changes prevent the channel from functioning properly and cells that line the passageways of the lungs, pancreas, and other organs produce mucus that is abnormally thick and sticky. The abnormal mucus obstructs the airways and glands, leading to the characteristic signs and symptoms of CF

Treatment of patients with cystic fibrosis is highly dependent on the gene mutation they carry.   Right now, Kalydeco is approved for a small subset of cystic fibrosis patients (4%) – those with a G551del mutation.  In patients with two F508del mutations, there is currently no treatment available that addresses the underlying cause of the disease and they account for approximately one-third of the cystic fibrosis patients.

The Studies

TRAFFIC and TRANSPORT were two global Phase 3, randomized, double-blind, placebo-controlled studies designed to evaluate the efficacy and safety of lumacaftor plus ivacaftor in people with cystic fibrosis ages 12 and older who have two copies of the F508del mutation. Each study included two combination treatment groups and one placebo group. 1,108 people enrolled and received at least one dose of study drug in the two studies (549 in TRAFFIC; 559 in TRANSPORT) at approximately 200 clinical trial sites throughout North America, Europe and Australia. The primary endpoint of TRAFFIC and TRANSPORT was the mean absolute change from baseline in percent predicted FEV1 at the end of the 24-week treatment period as assessed by the average change in lung function at Week 16 and at Week 24.  Several secondary endpoints were also shown to be statistically significant in the treatment groups and the treatment overall was found to be safe and well tolerated.

In a press release announcing these results, Bonnie Ramsey, M.D., Professor of Pediatrics, University of Washington School of Medicine, Director of the Center for Clinical and Translational Research at Seattle Children's Research Institute and a lead Principal Investigator for TRANSPORT said, “On average, people with CF who have two copies of the F508del mutation lose nearly two percent of their lung function each year, underscoring the urgent need for new medicines that address the underlying cause of this disease," adding,"These data showed consistent evidence of clinical benefit in lung function and other measures of the disease. The significant improvements in pulmonary exacerbations are particularly important given the potential for these events to result in hospitalizations, permanent lung damage and the need for additional treatment with antibiotics and other medicines."

Robert J. Beall, Ph.D., President and CEO, Cystic Fibrosis Foundation said, "These data mark an exciting day for the CF community and validate our more than 30-year commitment to develop medicines that target the underlying basic defect of cystic fibrosis for all people with this devastating disease."

Image of CF patient population and results  were obtained from Vertex webinar presented June 24,2014. Available at http://files.shareholder.com/downloads/VRTX/3273575852x0x764262/8000753b-8e62-47ef-af66-555b3aed672a/VRTX%20TRAFFIC%20and%20TRANSPORT%20Results%20Slides.pdf

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