In the News, May 2013: CFTR Modulators, Antibiotics, Mannitol, Infection Control

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Clinical Pipeline

 CFTR Modulators

 On April 18, Vertex Pharmaceuticals Inc. announced “headline” data from a Phase 2 study of its VX-661 “corrector” in combination with ivacaftor showing statistically significant improvements in lung function among adults with cystic fibrosis (CF) who have two copies of F508del. The study evaluated four dose levels of VX-661. Patients in the two highest dose groups (100 and 150 mg) showed statistically significant mean relative improvements in lung function (FEV1), versus placebo, of 9.0% and 7.5%, respectively, at Day 28. Lung function returned to baseline in all groups during the post-treatment 28-day period without medication. The primary endpoints of the study were safety, tolerability and change in sweat chloride. Change in lung function was measured as a secondary endpoint. There were statistically significant mean decreases in sweat chloride. More detailed results will be presented at the European CF Society conference in Lisbon, June 12-15.

Vertex confirmed that three correctors have been advanced from research into development – VX-809, VX-661 and VX-983. All these molecules aim to deliver sufficient levels of functional CFTR to the epithelial cell surface where it can be “potentiated” by ivacaftor. VX-809 is their lead corrector and is currently being tested in combination with ivacaftor as part of two on-going Phase 3 studies with 1,000 people aged 12 and older with two copies of the F508del mutation.

VX-661 is Vertex’s second corrector to enter clinical development. Vertex plans to conduct additional studies of VX-661 to further evaluate its potential for late-stage development, pending regulatory discussions. The company also said it has a third corrector, called VX-983, which has now entered clinical development and is currently being evaluated as part of a Phase 1 multiple-ascending-dose study in healthy volunteers. In the second half of 2013, Vertex plans to begin a 28-day Phase 2 study of VX-983 in combination with ivacaftor in people with two copies of the F508del.

VX-661 and VX-983 are close in their development timelines and Vertex plans to prioritize one of these compounds in 2014 for development in combination with ivacaftor and/or in potential dual corrector combinations. In addition to Vertex’s development activities focused on combinations of these “first-generation” correctors with ivacaftor, the company confirmed it has an active research program that has identified “second-generation” correctors that could be used as part of future triple combination regimens for people with CF.

We eagerly await the peer-reviewed published data for these studies as they become available.


As mentioned last time, Savara Pharmaceuticals Inc. have developed ‘AeroVanc ‘ for the treatment of persistent MRSA lung infection in cystic fibrosis (CF) patients.  They announced that the first patient has started study drug treatment in a Phase 2 clinical trial evaluating its safety and efficacy. Savara’s Phase 2 clinical trial is a randomized, double-blind, placebo-controlled study in 80 CF patients at 22 CF centres across the US. Study results are expected in Spring of 2014.

 Regulatory News

 Pharmaxis Ltd. confirmed that it had met the FDA and agreed the key measures for a further pivotal trial for dry powder mannitol (Bronchitol) in patients aged 18 and over in the US. This trial will have a very similar design to the two large scale Phase 3 clinical trials already undertaken by Pharmaxis. It will be of six months duration with improvement in lung function as measured by a change in FEV1 as its primary endpoint. Bronchitol is already approved for CF patients aged 6 and over in Australia and for adult patients with CF in the EU.

Other Research

Research utilising the latest genetic sequencing technologies and published by The Lancet on March 29 has revealed that Mycobacterium abscessus, a form of non-tuberculous mycobacterium (NTM), which had previously not been confirmed to be transferable between cystic fibrosis patients, is a potential cross-infection risk.  The research was carried out by Papworth Hospital and the Wellcome Trust. Whole genome sequencing and antimicrobial susceptibility testing were done on 168 consecutive isolates of M. abscessus from 31 patients attending an adult cystic fibrosis centre in the UK between 2007 and 2011. In parallel, the team undertook detailed environmental testing for NTM and defined potential opportunities for transmission between patients both in and out of hospital. The results suggested frequent transmission of NTM between patients with cystic fibrosis despite conventional cross-infection measures.

In response, the Cystic Fibrosis Trust has asked the NHS Commissioning Board’s Clinical Reference Group to work with them to review national guidelines to protect people with cystic fibrosis from cross-infection risks from this type of multidrug-resistant bacteria.


by Oli Rayner, May 2013