Cutting edge cell and gene therapies that hold the promise of transforming treatment of serious and rare diseases are within our grasp, yet a recent report found that Ireland remains an outlier among western European countries in preventing patients from accessing these ground-breaking treatments.
For Martin Schulz, senior medical director for the gene therapy platform at Pfizer Rare Diseases, his day job is working to help prepare and educate the healthcare community for the paradigm shift that gene therapy might represent for patients with rare genetic disorders. Schulz tells The Irish Times that he feels “privileged” to be working in such an exciting and dynamic field. A pharmacist by trade, he began working in research and development during his PhD and later entered Pfizer’s medical affairs department.
A special interest in haemophilia saw him exposed to gene therapy early on in its evolution, as this was one of the disease areas where the pioneering approach was first trialled.
“I had the opportunity to really follow that and now we are focusing on the broader gene therapy platform that potentially numerous rare disorders and patients could benefit from in the future,” he says.
Gene therapy is probably the most high-concept form of so-called “personalised” or “precision” medicine. As we learn more about the underlying genetic mechanisms of disease, we can deliver increasingly targeted treatments, tailored to the individual patient. It is the “next generation of medicine”, Schulz says.
“In the beginning of the last century we had medicines that focused on treating symptoms, then towards the end of the 20th century we had disease modifying agents. But what truly excites me is that now we are focusing on developing medicines that target the underlying cause of a genetic disease at a cellular level.”
At Pfizer, the initial focus is on rare genetic disorders caused by a single gene alteration, for example, in haemophilia A, haemophilia B, and Duchenne Muscular Dystrophy. Gene therapy essentially reprogrammes cells so that they can function normally, Schulz explains.
“What we do is that we deliver the functioning gene to the target tissue. We use a carrier called a recombinant adeno-associated viral vector that delivers the gene to the target cells, and enables the cells to produce the protein that has been missing or non-functioning,” he explains.
This means there is potential in gene therapy to offer patients long-term transformative clinical benefits and improve their quality of life, potentially with just a one-off treatment.
“Our hope for the future is that we may be able to treat various genetic rare disorders that currently have no or very limited treatment options. From a patient and caregiver perspective, these therapies have the potential to transform lives, and might significantly reduce the burden that is associated with a chronic, debilitating, or even life threatening disease,” Schulz adds.
Listening to the patient voice and understanding the true need from a patient perspective is incredibly important
It sounds almost miraculous, but he stresses that while gene therapy has been described as a “one and done” therapy, it isn’t quite that simple.
“It’s certainly not a ‘get and forget’ therapy because we need close follow up of these patients in the long term, to look at the durability of effect, to look at real world effectiveness, and to look at potential safety events as well.”
Another important caveat is that not every patient will be suitable for this form of therapy, he warns.
“Gene therapy is not a treatment option for every patient with a rare disorder. There are a number of things that need to be considered with regard to eligibility. These include the age of the patient, any comorbidities the patient might have, and whether the patient has antibodies to the vector that is being used, which could prevent treatment from working.”
Rare diseases may be individually rare, but collectively common – right now, worldwide, it is estimated that there are 400 million people living with a rare disease. Of the approximately 7,000 rare diseases that we know of, just five per cent currently have treatment options. Yet 80 per cent of rare diseases are genetic in origin and could thus represent targets for gene therapy.
It’s clear the patient is at the heart of this therapy, and Schulz notes that every effort has been made to include the patient voice at every stage as gene therapy has evolved.
“Listening to the patient voice and understanding the true need from a patient perspective is incredibly important. Quite often, the patients living with a particular rare disease, they are the true experts. We will always include patient insights all along the way, for example in clinical trial protocol development, when it comes to patient recruitment for clinical trials, and when it comes to education.”
One of the final hurdles with gene therapy will be integrating it into a health system model that is based around ongoing treatment. Significant policy and regulatory changes must be made to ensure patient access to these therapies after approval by EMA for those who will benefit from it, Schulz says.
“These challenges need to be addressed so that gene therapy can really develop its full potential. There is the feeling that science is outpacing the policymaking that needs to happen.”
According to the recent Pathfinder Study on the Adoption of Cell and Gene Therapies in Ireland, a new funding model for healthcare will be required as the long-term value of these treatments is considered.
To achieve the full potential of gene therapy we need to focus on the evolution of our healthcare systems
Schulz says novel reimbursement mechanisms such as those that look at staged payments connected to long-term patient outcomes could be an alternative to the current pay upfront model, although he notes that comprehensive patient registries and an embracing of real world data will be required in order to provide the data needed for such an approach.
Pfizer is committed to partnering with all stakeholders in the health ecosystem – from payers to regulators to medical societies and patient organisations to make this a reality, he adds.
“There's an urgency to this – an urgency for all stakeholders to work together and set this up and lay the groundwork for this new generation of treatment methods.”
By 2025, it is expected that between 10 and 20 gene therapies will be receiving regulatory approval per year. Gene therapy has a promising future if the science continues to deliver and the issues around policy and funding can be resolved, Schulz says.
“To achieve the full potential of gene therapy we need to focus on the evolution of our healthcare systems to accommodate potential one-time treatments with long term transformative clinical benefit. With Covid-19 we learned that acting quickly is key when there's an urgent medical need. And the same holds true for rare disease patients with limited or no treatment options who cannot wait – in Ireland and globally.”