Skip to main content
Premium Trial:

Request an Annual Quote

Vertex Says CF Patients with Double F508del Mutation Showing Improvement in VX-809/Kalydeco Trial


Vertex Pharmaceuticals has announced positive interim results this month from the second part of an ongoing Phase II trial examining a combined regimen of its approved drug Kalydeco and its newer treatment VX-809 in cystic fibrosis patients with the F508del mutation. After 56 days of treatment, adult subjects homozygous for the mutation have shown significant improvement in lung function, the company said.

According to Vertex, the new results are from a planned interim analysis of about half the full trial cohort — 37 patients homozygous for the mutation who received the combined treatment and 11 patients with either one or two copies of the mutation who received placebo.

The ongoing Phase II study is evaluating treatment of homozygous patients using a combination of Vertex's Kalydeco — approved last year by the US Food and Drug Administration for use in CF patients over 6 years old who have at least one copy of the G551D mutation in the CFTR gene — and VX-809, one of the investigational drugs in the company's pipeline.

Vertex is planning to release full results from the trial, covering a total of 108 subjects with one or two copies of the F508del mutation, later this year.

Cystic fibrosis is caused by mutations in the CFTR gene that result in defective or missing CFTR proteins, impairing the flow of salt and water into and out of cells. Approximately 90 percent of people with CF have at least one copy of the F508del mutation, and about 48 percent have two copies.

VX-809, called CFTR 'corrector,' is believed to help CFTR proteins reach the cell surface, while Kalydeco, a CFTR 'potentiator,' helps keep CFTR protein channels open (PGx Reporter 11/0/2011).

According to Vertex, the interim data from the combined therapy trial indicated that a majority of patients who received combined treatment had "significant improvement" in lung function relative to baseline.

The company said in its announcement that 17, or about half of the patients in the treatment group experienced an absolute improvement of five percent or more from baseline to Day 56. Another third of treated patients experienced an absolute improvement of 10 percent or more, while no patients in the placebo group showed five or more percent improvement.

According to the company, the analysis also found that "most adverse events were mild or moderate in severity and comparable between treatment and placebo groups."

Vertex plans to release full results from the trial later this year, including data from a group of heterozygous F508del patients receiving the combination therapy. At the time of the interim analysis not enough of these patients had completed the study to make any conclusions, the company said.

Chris Wright, Vertex's senior VP of global medicines development and medical affairs, said that after the company garners the complete data from this study, it will start discussion with regulatory agencies, "with the goal of moving forward with a pivotal study as quickly as possible."

According to the announcement, Vertex is planning a pivotal study of VX-809 and Kalydeco in homozygous F508del patients "pending final study results and discussions with regulatory agencies."

The Scan

Study Links Evolution of Longevity, Social Organization in Mammals

With the help of comparative phylogenetics and transcriptomics, researchers in Nature Communications see ties between lifespan and social organization in mammals.

Tumor Microenvironment Immune Score Provides Immunotherapy Response, Prognostic Insights

Using multiple in situ analyses and RNA sequence data, researchers in eBioMedicine have developed a score associated with immunotherapy response or survival.

CRISPR-Based Method for Finding Cancer-Associated Exosomal MicroRNAs in Blood

A team from China presents in ACS Sensors a liposome-mediated membrane fusion strategy for detecting miRNAs carried in exosomes in the blood with a CRISPR-mediated reporter system.

Drug Response Variants May Be Distinct in Somatic, Germline Samples

Based on variants from across 21 drug response genes, researchers in The Pharmacogenomics Journal suspect that tumor-only DNA sequences may miss drug response clues found in the germline.