As many of you will know, the UK CF Gene Therapy Consortium (GTC) has brought together teams at Imperial College London and the Universities of Oxford and Edinburgh to vigorously pursue a single goal for the last 17 years, namely to establish whether gene therapy can become a clinically viable option for patients with CF. This form of treatment needs new copies of the CF gene to be introduced into the cells lining the lung, which is hard to achieve because these cells have evolved to keep external molecules out. The CF gene has to be carried past these defences, achievable either by surrounding it with fat (liposomes) or by inserting the CF gene inside a viral vector. Because of these defences, the GTC anticipated that successful gene therapy would require us to investigate several products, with incremental increases in knowledge helping us to overcome these barriers. We introduced the terms Wave 1 (the best liposome available at that time), and Wave 2 (the best viral vector we believe is currently available).

 

Supported by the CF community, and thereby predominantly funded by the Cystic Fibrosis Trust, we developed the Wave 1 product (the CF gene delivered via a liposome). Subsequently, funded by the National Institute for Health Research’s Efficacy and Mechanism Evaluation (EME) programme, we were able for the first time to demonstrate a significant benefit in lung function compared with placebo in the world’s largest CF gene therapy trial. Since the trial ended, we have spent considerable time presenting the product to the pharmaceutical industry, as it is these companies who have the resources to carry it through to the next step. The consistent response was that whilst they are impressed with the data, they wish to see a higher level of efficacy (which was slightly less than that produced by Orkambi). This boost could be produced by increasing the dose, increasing the dosing frequency, or trying a different type of liposome. We are exploring these possibilities and if this can be achieved, we will reopen these negotiations with a view to supporting a further clinical trial.

 

In parallel, we have been working for over a decade with a Japanese biotechnology company (DNAVEC, now called ID Pharma), building on knowledge from the Wave 1 programme, and have developed an alternative viral vector to deliver the CF gene (Wave 2 product). Support from the MRC DPFS programme and the Cystic Fibrosis Trust has brought this product to a stage where it can now undergo toxicology testing and larger-scale manufacturing; we have also recently received funding from the Health Innovation Challenge Fund, a collaboration between the Wellcome Trust and the Department of Health and Social Care, to undertake the next steps. We would also like to take this opportunity to warmly thank all of our supporters over many years, including Just Gene Therapy and Flutterby FUNdraisers.

 

It is now with great pleasure and excitement that we can add the next piece of the puzzle. The GTC is joining forces with two world class organisations in a major collaboration. We will work in partnership with Boehringer Ingelheim, who are an internationally renowned ‘big pharma’ company with substantial expertise in bringing products through to patients, including in the respiratory field, and also with Oxford BioMedica who are the acknowledged leaders in the field of manufacturing the type of virus we have established as our Wave 2 product. The three partners are coming together to translate the Wave 2 product into clinical trials, and if successful, into routine clinical practice.

 

The GTC believes that this partnership provides CF patients with the optimal chance to establish gene therapy as routine clinical practice, relevant to all patients irrespective of their mutation status, and in due course to both prevent lung disease as well as treat established problems. Importantly, we can of course offer no guarantee of success, building this programme will not happen overnight and the therapy will only be focused on the problems occurring in the lungs.

 

We believe this new partnership of three world leading organisations has the greatest chance of realising a parallel new therapeutic pathway for CF patients, and better still, one that will add to the improvements already being seen with small molecule treatments. The gene therapy may have additional benefits: currently we envisage the effect of a single dose lasting for many months or even longer and it is unlikely that gene therapy will suffer from drug-drug interactions. We will regularly update on progress on this website as this exciting programme now unfolds.