The future of gene therapy

bluebird bio’s chief scientific officer answers the biggest questions on gene therapies in the UK.

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Philip Gregory has served as the chief scientific officer at gene therapy company bluebird bio since June 2015. Philip holds a D. Phil in biochemistry from Keble College, University of Oxford and a BSc in microbiology from the University of Sheffield, and was a postdoctoral fellow at Ludwig-Maximilians-Universität München. He has held various research and leadership roles during his career.

What is gene therapy and can you explain how it works?

The goal of gene therapy is to address a disease at its genetic level. Many different approaches are being studied, such as turning off genes that are causing problems or replacing a defective gene by adding a functional version to help do the work of a defective gene. bluebird bio is working on an approach to gene therapy that adds functional copies of a faulty gene to a patient’s own blood stem cells – called gene addition. First, stem cells are taken from the patient’s body. Then the functional copies of the gene are delivered into the patient’s blood stem cells outside of the patient’s body, at our manufacturing site – a process known as “ex-vivo” as it takes place outside the patient’s body, in a laboratory. This is gene therapy.

The gene therapy is then given to the patient via a stem cell (or bone marrow) transplant.  In hospital, the patient first receives chemotherapy to make room in their bone marrow for the gene therapy. After the gene therapy has been infused, the patient’s cells will need time to multiply and produce enough new stem cells with the functional gene. This process is called engraftment.

From their home in the bone marrow these gene-modified stem cells can give rise to all the different cell types found in the blood. The patient remains in the hospital until their immune system cells have recovered and their doctor determines that it is safe for the patient to be discharged. The corrected gene-modified cells restore the defective function of the patient’s cells and hopefully will eliminate the signs and symptoms of their underlying disease.

What attracted you to join a company like bluebird bio?

I have been working in cell and gene therapy for 20 years and was aware of bluebird bio well before the opportunity to join them came up. There are several things that make bluebird bio special. First is that we make use of different technologies to make the best therapies possible. We do not necessarily focus on just one technology such as gene addition and gene editing. Instead the emphasis is on making the best possible therapies for patients, regardless of the technology.

Next is bluebird bio’s ability to translate innovative science from the bench into the clinic where patients can potentially benefit from it. These cutting-edge techniques are hugely complex to put into practice on a large scale, but bluebird bio is dedicated to making that happen.

Importantly, what made bluebird bio stand out to me was that underpinning the incredible drive and commitment to innovative science is the company’s focus on patients. This is led by the management team and it was this absolute dedication to patient-centricity that made me realise this was somewhere I really wanted to work.

What excites you about gene therapy?

I’m excited by the potential of gene therapy to both change the conventional symptomatic approach to disease treatment as well as provide options for diseases that cannot be treated in any other way. We are at an immensely exciting moment in time with CAR-T treatments and treatments for ADA-SCID (an inherited disorder that damages the immune system and causes severe combined immunodeficiency) and LCA (an inherited retinal disease) already approved. Many more are in the pipeline. Most importantly, we are on the cusp of gene therapy becoming more available to patients.

Healthcare providers may have the ability to treat a host of rare diseases which until now have had limited, if any, viable treatment options, and really change the lives of patients, their families and carers, for the better. In the UK, one in 17 people, or almost six per cent of the population, will be affected by a rare disease at some point in their lives – around 3.5 million people in the UK.

Gene therapy is fundamentally a different prospect for many patients. The goal is to address the underlying cause of disease through a one-time treatment.

What do you consider to be some of the challenges around the task of commercialising gene therapy?

Clearly the regulatory environment is a critical factor, but the FDA and EMA have both been incredibly supportive of gene therapies. The key has been their openness to talk with companies like bluebird bio – something that we have tried to do as often and as early as possible in the development process.

Another potential challenge is the inherent difficulty of manufacturing gene therapies and doing so at scale. This is why we are investing in cutting-edge process which combines working with specialist hospitals and our manufacturing network, supported by a comprehensive training programme for clinical staff who are involved in the process of extracting the patients’ cells at the beginning of the treatment and then administering the gene therapy at the final stage. There are also significant logistical and scheduling challenges in getting the therapy from A to B. We are learning a great deal from the established CAR-T treatments, but this is a complex supply chain and our goal is to ensure the process works as efficiently and effectively as possible.

How will UK patients gain access to gene therapy?

The long-term aspiration of gene therapy is that, ideally, after a single treatment, a patient will have reduced ongoing interventions. Given that the UK has a single-payer system, the NHS, the value of that single therapy can potentially be understood more easily because it is able to take a more holistic view of the benefit derived by the patient and the value this represents.

Payers are already showing willingness to discuss an instalment-based reimbursement model based on the treatment’s value and we believe this is really important. For example, bluebird bio has publicly stated its willingness to put agreements in place that enable commissioners to pay over a maximum five-year horizon – not the rest of a patient’s life even if we expect a lifetime of benefit for patients. These payments would be to specific outcomes which equate to clinical benefits to patients. This also means underwriting some of the uncertainty by sharing the financial risk.

This would mean that the NHS would only have to pay instalments for treatment that has been successful in which patients continue to achieve pre-agreed outcomes. This is an ongoing conversation and one we are actively participating in.