What is your background and current role?
I joined the bluebird bio ‘flock’ as head of Europe in 2016. In my current role, I am responsible for overseeing our European expansion plans as we develop from a clinical stage to a commercial stage biotech company.
We are finally able to explore techniques that harness the body’s own cells to treat the underlying genetic cause of disease and bluebird bio is working to make this a reality in the clinical setting. I am responsible for developing and scaling up the European business in preparation for the European launch of our gene therapies.
Prior to joining bluebird bio, I worked at Shire in Paris where I was the General Manager of France and Benelux overseeing a portfolio including seven rare disease products. Before that, I spent eight years at Genzyme and Sanofi holding roles of increasing responsibility in business development, marketing and global commercial operations. My background is in genetics – I received a BA in genetics, cell and developmental biology from Dartmouth College, followed by an MBA from North-western University’s Kellogg School of Management.
What is the history of the company?
Headquartered in Cambridge (Massachusetts, US), our European headquarters are in Zug, Switzerland. We have a strong commitment to Europe and are establishing operations in Italy, Germany, France and the UK.
We have always believed in the potential of gene therapy. Our integrated product platforms encompass gene therapy, cancer immunotherapy and gene editing. Our goal is to submit four ground-breaking gene therapies for regulatory approval by 2022 – with the potential to transform the lives of people living with certain rare genetic diseases. bluebird bio’s first Marketing Authorisation Application was submitted and accepted for review by the European Medicines Agency in October 2018, and received a positive CHMP Opinion at the end of March 2019.
Tell us about some of the rare genetic diseases bluebird bio is focusing on?
The most obvious first target for developing gene therapy is ‘monogenetic diseases’, these are diseases caused by one malfunctioning copy of a gene. ß-thalassaemia and Sickle Cell are the most prominent monogenetic diseases and this is one of the reasons we have decided to focus on them. Although treatments available today help manage these conditions, options are limited and there is still a significant unmet need. Transfusion-dependent beta-thalassaemia (TDT) affects 1 in 100,000 people throughout the world per annum and 1 in 10,000 people in the European Union per annum. The emotional cost to the patient and his or her family is self-evident, but the long-term socio-economic impact of a life-long treatment regime on society can also be significant.
What are your gene therapies and their mechanism of action?
The goal of gene therapy is to address a disease at the genetic level. There are many different approaches to gene therapy which are being studied today. These include turning off genes that are causing problems, replacing a defective gene with a functional gene and adding functional genes to help do the work of a defective gene. bluebird bio scientists are exploring multiple gene therapy techniques, but our most advanced investigational treatment adds functional copies of a faulty gene to a patient’s own blood stem cells. This therapy has taken over ten years to research and develop as a way to target the cause rather than the symptoms of disease. We reported in 2010 (Cavazzana-Calvo et al, Nature) about the first TDT patient to become independent of transfusions after gene therapy, and in 2017 published some clinical data for one-time treatment of sickle cell disease (Ribeil et al, NEJM).
We begin by extracting the patient’s stem cells by apheresis. Then the cells are frozen and transported to our manufacturing site in Germany where, using a modified virus as a delivery vehicle (a ‘lentiviral vector’), genetic information is inserted into the haematopoietic stem cells (HSCs). The modified cells carrying functional copies of the relevant gene are then put back into the patient following chemotherapy which makes space in the bone marrow compartment. The modified cells then multiply and produce new cells with the functional gene. Following the treatment, the patient remains in hospital while his or her immune system recovers. Our gene therapy is administered using a process called ‘autologous haematopoietic stem cell transplant’ (HSCT) which involves the patient’s own cells. This type of gene therapy uses a technique known as ‘gene addition’.
What do you expect to be the key challenges in getting a gene therapy from the research stage to the patient in Europe?
Gene therapy is a disruptive technology which will potentially mark a new chapter in approaches to treating genetic diseases. But this isn’t just about transforming clinical outcomes. The advent of gene therapy also calls for new approaches to the way that treatments are evaluated and reimbursed to ensure that the patients get rapid access. This will be a critical part of getting these new treatments from ‘bench’ to ‘bedside’.
From a regulatory standpoint, I’m pleased to say that EMA has been incredibly supportive of the concept of gene therapies and has been open to establishing an early dialogue with companies like bluebird bio. However, in general, if we are going to get gene therapy into the clinic, all European health systems need to be ready to work collaboratively with industry to remove potential barriers. All parties need to be willing to move away from the traditional approaches adopted for chronic therapies towards one which reflects the specific nature of one-time rare disease medicines. This also requires industry to be creative, flexible and willing to share risk when it comes to possible payment mechanisms.
One example is the concept of outcome-based commercial agreements to enable commissioners to pay over an extended period (for example a five-year window), tied to specific clinical outcomes. Such an approach requires industry to underwrite some of the uncertainty which could otherwise be a barrier to achieving reimbursement. At bluebird bio this is something we take very seriously and have publicly stated that we are prepared to put the majority of the price of our therapies at risk, meaning we will only get paid if our treatments perform over time.
What are your future goals/plans?
Our goal is to bring gene therapy to patients with unmet medical need. Many pharmaceutical companies who have initially explored this space have subsequently moved on to other areas, but for us gene therapy is our core purpose and this is something which really sets bluebird bio apart. The CHMP of the EMA adopted a positive opinion recommending conditional marketing authorisation for our first therapy at the end of March 2019, and we expect our first commercial treatment to be launched in Europe soon after. We believe that gene therapy as a potentially one-time treatment will open a new chapter in the approach to tackling rare genetic diseases.
In the same way as we are pioneering new treatments, at bluebird bio we also want to lead the way in shaping new payment and reimbursement models for gene therapies which are sensitive to the financial pressures that European healthcare systems face. Therefore, even as a clinical-stage company, we are working to prepare the groundwork and engage early with health systems across Europe so that when the time is right we can partner to create payment systems which offer value and can be adapted to suit local needs.
