Oral pill to treat cystic fibrosis VX-809 by Vertex in human trials

VX-809, an oral investigational drug to treat cystic fibrosis, has shown encouraging results in early phase clinical studies, Vertex Pharmaceuticals announced.

VX-809 is a cystic fibrosis transmembrane conductance regulator protein (CFTR) corrector.

In a 28-day Phase 2a clinical trial, VX-809 showed a statistically significant decline in sweat chloride at both the 100 mg and 200 mg once-daily doses, suggesting that the activity of the CFTR protein was increased in patients during dosing.

VX-809 has also demonstrated a dose response in change in sweat chloride across the four dose groups.

Vertex now plans to initiate a combination trial of VX-809 and VX-770, an investigational CFTR potentiator, in the second half of 2010.

VX-809 and VX-770 were developed with support from Cystic Fibrosis Foundation Therapeutics, Inc., the nonprofit affiliate of the Cystic Fibrosis Foundation.

“This Phase 2a trial evaluated the potential effect of an oral compound to improve trafficking of the defective CFTR protein, and its results represent an encouraging step forward in the development of new therapies to treat the underlying cause of CF in patients with the most common CFTR mutation, known as F508del,” stated J.P. Clancy, MD, Director of the Pediatric Pulmonary Center at the University of Alabama at Birmingham and Principal Investigator for the VX-809 Phase 2a trial.

In the trial, VX-809 was well-tolerated across the dose groups, and statistically significant changes in sweat chloride, an important biomarker of CFTR activity, were observed at certain dose levels.

Cystic fibrosis is a life-threatening genetic disease affecting approximately 30,000 people in the United States and 70,000 people worldwide. Mutations in the CFTR gene cause patients with CF to have defective or missing CFTR proteins at their cell surfaces. These defective or missing CFTR proteins result in poor chloride ion flow across cell membranes, causing the body to produce abnormally thick, sticky mucus that leads to chronic, life-threatening lung infections.

Today, the median predicted age of survival for a person with CF is more than 37 years.

Approximately four percent of the total CF patient population in the U.S. have the G551D mutation on at least one allele, 49 percent of the total CF patient population in the U.S. are homozygous for the F508del mutation and an additional approximately 38 percent of the total CF patient population are heterozygous for the F508del mutation, according to the 2007 Cystic Fibrosis Foundation Patient Registry Annual Data Report.

Currently, there are no approved therapies that directly target the underlying defect of cystic fibrosis.

Compounds such as VX-770 and VX-809 represent a promising potential approach to future cystic fibrosis treatment, said Vertex officials.

Vertex’ VX-809 trial with combination drug VX-770 expected to begin later this year.

Vertex initiated its CF research program in 1998 as a part of a collaboration with Collaborative History with Cystic Fibrosis Foundation Therapeutics, Inc., the non-profit drug discovery and development affiliate of the Cystic Fibrosis Foundation.

Vertex and CFFT expanded the agreement in 2000 and again in 2004, and in March 2006, entered into a collaboration for the accelerated development of VX-770.

In addition to the development collaboration for VX-770, in January 2006 Vertex and CFFT entered into an expanded research collaboration to develop novel corrector compounds. Vertex has received approximately $75 million from CFFT to support CF research and development efforts.

The Cystic Fibrosis Foundation is the world’s leader in the search for a cure for cystic fibrosis. Based in Bethesda, Md., the Foundation also supports and accredits a national care center network that has been recognized by the National Institutes of Health as a model of care for a chronic disease.

Vertex Pharmaceuticals Incorporated is a biotechnology company developing small molecule drugs for serious diseases.

Vertex’s product pipeline is focused on viral diseases, cystic fibrosis, inflammation, autoimmune diseases, epilepsy, cancer, and pain. Vertex co-discovered the HIV protease inhibitor, Lexiva, with GlaxoSmithKline.