Rare diseases are more common than you might think. The World Health Organization (WHO) gives the rough estimate that about one in fifteen people worldwide could be affected by a rare or orphan disease. This equates to 400 million people worldwide, with 30 million in Europe and 25 million in the United States. These 400 million are affected by one of the between 5,000–8,000 rare diseases, some of which we know more about than others and most of them with a genetic basis. Many of the diseases in this group have a deep impact on the lives of patients and their families, and very few have any form of approved treatment available.
As our understanding of these diseases has grown in parallel with developments in genome sequencing, so has our understanding of how to potentially treat them using personalised gene therapies.
Treatments such as those recently launched to treat cancer are ground-breaking in themselves, but represent only the very tip of the iceberg. With many personalised therapies in the pipeline for a wide variety of different conditions, the next few years are set to be busy for the regulators charged with assessing these novel treatments. We are potentially on the cusp of gene therapy becoming more widely available to patients.
The goal of gene therapy is to address a disease at the genetic level. Many different approaches are being studied, such as 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.
One investigational approach utilising gene therapy adds functional copies of a faulty gene to a patient’s own stem cells through a process called ‘gene addition’. First, stem cells are taken from the patient’s body to a manufacturing laboratory where functional copies of the gene are delivered into the patient’s stem cells. This process makes the gene therapy.
The therapy is then transported back to the patient and administered via a stem cell or bone marrow transplant. In hospital, the patient first receives chemotherapy to make room in their bone marrow. 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. The patient remains in the hospital until their immune system has restored and their doctor determines that it is safe for them to be discharged.
Now that the science has been developed in the laboratory, the next hurdles to overcome are around how to bring it into clinics and to patients. The investigational ‘ex-vivo’ gene addition technique I described above harnesses the power of the patient’s body to make their own personalised treatment.
Due to this highly specialised process central manufacturing laboratories are often utilised by companies, so we have many practical steps to consider. The patient is the start and end point and everything that comes in between including the complexity of the supply chain and training clinical staff needs to be put in place and be scalable. The clinical teams and the manufacturing teams need to be in constant communication and perfect alignment. We are learning from the established CAR-T treatments and our goal is to achieve access for patients as quickly as possible after approval by the regulatory authorities to include local approvals as well.
Gene therapy offers a new approach to treating disease because ideally it only needs to be administered once and has the potential to offer a lifetime of patient benefit.
This new treatment paradigm requires access stakeholders to reconsider how they assess and pay for these treatments. One important aspect of this is the need for an instalment-based reimbursement model, one where manufacturers only receive payment if a pre-determined outcome measure is achieved. Outcomes-based pricing could offer a fairer, sustainable, and more transparent approach to this complex issue.
Outcome-based pricing works whereby manufacturers and payers agree on key patient-relevant performance indicators and a commensurate instalment payment for the pre-agreed targets. For example, assuming a five-year time window, a health system could agree to pay for the cost of a treatment for the first year at administration and from then on only pay the remainder if the pre-agreed outcomes are achieved. This would allow it to enable access to treatments that could give patients the hope of a better quality of life, but only pay when those benefits are actually realised by an agreed methodology.
We have said that we are willing to share the financial risk via innovative strategies, like those mentioned above, and we completely acknowledge that healthcare systems have their own well-established ways to assess and pay for treatments. We contend that the introduction of these new therapies warrants reconsideration of approaches largely designed for delivery of chronic therapy. We want to work in collaboration with access stakeholders to pilot new ideas and approaches that reflect local healthcare system preferences for granting access, while considering the need for new or amended approaches that reflect the unique aspects of a new generation of gene therapies.
The Food and Drug Administration (FDA) and European Medicines Agency (EMA) have 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.
However, there are challenges when it comes to the appraisal and assessment processes that these treatments must be subject to before they can be licensed and made available to patients.
Although the rare disease patient population is larger than most people would anticipate, it is still relatively small when compared to other conditions and diseases. This can pose challenges when being assessed by national regulators.
Offering more flexible health authority assessment processes of rare diseases would potentially be to the advantage of rare disease patients by ensuring that personalised gene therapies could become a viable choice for the people who need them.
Doug Danison has led the global market access function at bluebird bio since 2015. Previously he was head of global pricing and market access at Takeda Oncology and global reimbursement director at Amgen. Doug holds a BS in Finance from Miami University and an MBA in Marketing from Ohio State University, The Max M Fisher College of Business.