In the News – October 2013: NACFC, CFTR Modulators, Ataluren, Personalised Medicine and Lynovex

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North American CF Conference

The NACF conference took place in Salt Lake City, Utah from 17th to 19th October 2013.

The main events were the three Plenary Sessions:

Plenary I – Restoring CFTR Function

Plenary II – Clinical Research Pathway to Ensure that All Patients with CF Benefit from Novel Therapies

Plenary III – CFRD: From Bench to Bedside & Back Again

Click here to watch the archived recordings

CFTR correctors and potentiators

At NACFC, Vertex provided an update on their programme to extend the use of Ivacaftor, as a single agent and in combination with correctors, to a broader range of CF mutations.

Non-G551D gating mutations

Based on positive trial data earlier in the year, an application has been submitted to FDA (US) and EMA (Europe) to extend the use of Ivacaftor (Kalydeco), as a single agent, to people with CF aged 6 and older with a non G551D gating mutation. There are approximately 400 people aged 6 and older with a non G551D gating mutation in North America, Europe and Australia. The Phase 3 study of Ivacaftor in 2-5 year olds with gating mutations is fully enrolled and ongoing. Data from this study is expected in the Summer of 2014. There are approximately 300 children in this category in North America, Europe and Australia.


The Phase 3 study of Ivacaftor in those with the R117H mutation is fully enrolled and data is expected by the end of 2013. There are approximately 360 people in the UK with the R117H mutation. R117H is a residual function mutation which means people with this mutation can have very mild CF. Vertex is conducting a Phase 2 clinical study of Ivacaftor in people with residual function mutations other than R117H aged 6 and older. Enrollment to this study is complete and data is expected in Summer 2014. More than 3,000 people aged 6 and older have a non R117H residual function mutation in North America, Europe and Australia.


For those with two copies of F508del, the Phase 3 (TRAFFIC and TRANSPORT) studies of VX-809 (or Lumacaftor) in combination with Ivacaftor recruited very quickly and data from the trial is expected in the middle of 2014. The trial involves 1,000 patients aged 12 and older globally. Subject to results, Vertex plan to submit an application to the FDA and EMA in the second half of 2014.

There is a Phase 2 study of VX-809 in combination with Ivacaftor for children aged 6 to 11 with two copies of the F508del mutation. Dosing is complete in the pharmacokinetics part of this study and enrollment in the second part is expected in Spring 2014.

Vertex recently began enrollment in an 8-week exploratory Phase 2 study of VX-809 in combination with Ivacaftor in people 18 and older with one copy of the F508del mutation on one allele and a second mutation that is not expected to respond to either Ivacaftor or VX-809 alone.

Following discussions with regulatory authorities, Vertex is preparing to conduct a 12-week study of VX-661 in combination with Ivacaftor in people with CF who have two copies of the F508del mutation. Enrollment in this study is expected to begin in Spring of 2014.

G551D & dF508

Vertex recently began recruiting in a Phase 2 study evaluating a 4-week regimen of VX-661 in combination with Ivacaftor in people with one copy of the G551D mutation and one copy of the F508del mutation. This is the first proof-of-concept study of a combination of a corrector and Ivacaftor in people with these mutations. This study is intended to explore whether the addition of a corrector to treatment with Ivacaftor can further enhance the clinical benefit received from Ivacaftor alone in people with the G551D and F508del mutations. This combination treatment regimen is supported by laboratory data showing enhanced CFTR function with the combination of VX-661 and Ivacaftor. Data from this study are expected in Spring of 2014.

Vertex aims to advance a next-generation corrector into clinical development by the end of 2014. Next-generation correctors could be evaluated as part of potential dual-corrector regimens i.e. a triple combination of Ivacaftor plus a first generation corrector (VX-809 or VX-661) plus a second generation corrector. The proposed use of a dual-corrector combination regimen is supported by laboratory data that showed a combination of two correctors with Ivacaftor increased chloride transport in human bronchial epithelial cells with one or two copies of the F508del mutation, as compared to the use of a single corrector in combination with Ivacaftor.

Ataluren – a further Phase 3 trial in 2014

PTC Therapeutics provided an update on their plans for Ataluren (PTC124). Ataluren aims to correct the underlying genetic defect in people with CF Class 1 nonsense mutations. Approximately 10% of people with CF have these mutations. Earlier Phase 3 results showed a 3% improvement in FEV1 compared to placebo at 48 weeks which was not statistically significant, however those not on inhaled Tobramycin showed a 6% FEV1 improvement. PTC think that tobramycin interferes with Ataluren’s mechanism of action and reduces clinical efficacy. Overall there was a 23% reduction in pulmonary exacerbations, which increased to 41% for patients not on inhaled tobramycin. The company announced that they will carry out a further Phase 3 clinical trial in the first half of 2014. The planned trial will exclude patients who are receiving chronic inhaled aminoglycoside antibiotics such as Tobramycin but other details of the trial design are currently being discussed with regulators in the US and EU.

Personalised Medicine

A new €6 million global research programme funded by the EU to develop new ways to treat cystic fibrosis. The new programme, known as CF Matters, aims to develop personalised antibiotic treatments for CF chest infections. The work could have a major impact on the way antibiotics are prescribed and help limit resistance to the drugs.

The study brings together renowned CF clinicians and scientists from 12 academic institutions and hospitals across Europe and the USA. It is led by University College Cork with Queen’s University Belfast as a lead partner. It will involve lab-based research and clinical trials with 252 patients in seven countries. Queen’s lead on the study is Professor Stuart Elborn, Director of Queen’s Centre for Infection and Immunity.

Professor Elborn said:

“When patients have a flare-up they are treated with several antibiotics but it isn’t always effective and can lead to antibiotic resistance. In this study we will use molecular next generation DNA sequencing methods to detect all the bacteria present in the sputum of CF patients and use this knowledge to determine what antibiotics should be used in individual patients.”

“This personalised antibiotic treatment will be compared with standard therapy for CF patients. We will determine the patient’s immune response to all the different bacteria present in the sputum. Using models of infection we will also discover the effect of these bacteria on lung inflammation and infection. The overall impact will be to determine if all bacteria present contribute significantly to lung infection in CF patients and subsequently identify the most effective antibiotic treatment for patients infected with these bacteria.”

Previously, the Cystic Fibrosis Trust funded Professor Elborn via grant which allowed him to participate in the early stages of this EU collaboration, develop this project and secure this much larger grant.

Lynovex – novel treatment for persistent infection

Novabiotics partnered with the Cystic Fibrosis Trust and Health Sciences Scotland for a Phase 1/2a clinical trial of Lynovex. Lynovex is being developed to treat persistent lung infection in people with CF. It uses a novel peptide-based approach which breaks down excessive mucus, penetrates biofilms and kills bacteria in a way that prevents them establishing antibiotic resistant infections. The drug is already approved for oral delivery in an unrelated disease and has been shown to be safe and well tolerated so it has the potential for fast track clinical development. Trials will begin in the New Year with results expected at the end of 2014.

by Oli Rayner, November 2013