Research Update

Witten by: Andrea N. Flynn, Ph.D.

Vertex Submits New Drug Application to the FDA

Vertex recently announced encouraging data from the Phase 3 TRAFFIC and TRANSPORT studies of lumacaftor in combination with ivacaftor. Lumacaftor is a cystic fibrosis transmembrane conductance regulator (CFTR) ‘corrector’ that aims to address issues in the processing and trafficking of the CFTR protein so it can reach the cell surface. Ivacaftor is a CFTR ‘potentiator’ and aims to further enhance the ion channel function of the CFTR protein. Therefore, once lumacaftor properly positions the CFTR protein at the cell membrane, ivacaftor can help it to increase the necessary transport of salt and water across the cell, correcting the basic defect that is central to CF.

Participants in the study were individuals ages 12 and older with two copies of the F508del CFTR mutation. The results showed improvements in lung function and pulmonary exacerbations through a total of 48 weeks of treatment. Vertex recently announced that they have used this promising data to submit a New Drug Application (NDA) for the combination treatment of lumacaftor and ivacaftor in individuals with cystic fibrosis ages 12 and older who have two copies of the F508del mutation in the CFTR gene to the U.S. Food and Drug Administration (FDA). As many as 22,000 individuals with CF could benefit from the combination therapy and the NDA submission represents an exciting step forward.

Jeffrey Chodakewitz, M.D., Executive Vice President and Chief Medical Officer at Vertex said, "The combination of lumacaftor and ivacaftor is the first potential treatment designed to target the underlying cause of cystic fibrosis in people with two copies of the F508del mutation, which is the most common form of the disease.” Dr. Chodakewitz went on to say that the FDA submission represents important progress toward Vertex’s ongoing efforts to develop new medicines for the vast majority of people with cystic fibrosis, and Vertex looks forward to working closely with regulatory agencies to bring this treatment to eligible patients as quickly as possible.

PTC Therapeutics Starts New Phase 3 Trial for Ataluren

PTC Therapeutics recently announced they have initiated the Ataluren Confirmatory Trial in Cystic Fibrosis, or ACT CF, a Phase 3 clinical trial of ataluren (formerly PTC124) in individuals ages 6 or older with nonsense mutation cystic fibrosis (nmCF). ACT CF is an international clinical trial to assess the safety and effecicacy of ataluren on lung function in patients with nmCF. The study plans to enroll 208 patients for 48 weeks and PTC expects that individuals who participate in the study will have the opportunity to continue to receive ataluren in an additional extension study. Detailed information on enrollment criteria is available at www.clinicaltrials.gov. More information is also available at the PTC Therapeutics Patient and Professional Advocacy line, (866) 282-5873, or at PatientInfo@ptcbio.com.

Early Stage Research on New Drug Combination Shows Promise

A group of researchers in Scotland, Italy and France have identified a new drug combination that reduces airway inflammation and restores ion transport in the airways of individuals with CF. The small Phase 2 study included only 10 participants and was not placebo-controlled. However, early results indicate that the combination of two drugs, cysteamine and epigallocatechin gallate (EGCG), an antioxidant common in green tea, improved inflammation and reduced the amount of salt in the sweat of 9 of the 10 participants. Researchers are now planning a larger-scale, placebo-controlled clinical trial to further investigate the combination treatment in an international population of individuals with CF and at least one copy of the F508del-CFTR gene.