In March we recognize Bleeding Disorders Awareness Month and the communities affected by these conditions, including hemophilia. As we continue to advance our efforts toward a durable, redosable gene therapy for hemophilia A, we reflect on how we hope to serve these communities.
As part of this, we spoke with Doug Kerr, chief medical officer of Generation Bio, about his vision of a new paradigm in treatment for hemophilia.
As a clinician and scientist, my whole career has been centered around genetic disease. I was working in this space, including working on AAV gene therapy programs, and increasingly began to see the limitations of current approaches, like the inability to deliver large genes or redose, to name a few. I knew there needed to be a better way.
At Generation Bio I saw the opportunity to invent that new way. I really saw this as an opportunity to build upon AAV gene therapy and impact more patients more completely. Generation Bio is working towards a platform with so much potential: You could re-dose at the outset of therapy to calibrate the expression level for each patient, re-dose with the same medicine in the future if needed, and scale up to treat not just rare, but also common diseases all around the world. I joined the team as one of the earliest employees to help advance the science so we could move toward treating people.
Our work aims to change the way we treat genetic disease entirely. It’s a revolutionary vision for people living with hemophilia and those living with many other rare and prevalent genetic diseases.
My own role at the company has evolved as our research has advanced. I joined as chief scientific officer, moved to chief development officer when our programs matured into the translational phase, and recently took on role of chief medical officer as we prepare to enter the clinic.
I have to first say that the field has come a long way towards developing a disease-modifying treatment, and the outlook for hemophilia patients is far better than it used to be – but there is a long road ahead.
Individuals with hemophilia are burdened with the need for regular infusions. There are now long-acting factors, but they still have to be administered two to three times a week, which means that people with hemophilia can never forget about their disease. It’s always on their minds.
I’ve also heard feedback from the community that there’s a lot of frustration about the one-size-fits-all nature of current gene therapy approaches. Every patient has a different need, based on his or her activity level, tolerance for risk and other factors. Yet you can’t customize the current treatments to individual needs.
Another challenge is getting treatment to those who need it. In fact, approximately 75% of hemophilia A patients worldwide still receive inadequate treatment or have no access to treatment at all.
This is a major reason why hemophilia A is our lead program. We believe this is an opportunity to really make a difference in the lives of patients. Our goals are to free them from a lifetime of chronic treatment and to deliver a lifetime of protection from bleeds.
Our goal is to develop a treatment that will allow patients to live their lives and forget about the disease in a way that they currently cannot.
To do this, we’re developing a non-viral gene therapy for hemophilia A that is designed to be titratable, durable and redosable, if needed. Our platform uses a construct called closed-ended DNA, or ceDNA, to hold a functional factor VIII gene, and we plan to deliver this to a patient’s cells using cell targeted lipid nanoparticles, or ctLNPs.
Because our delivery system is non-viral, we believe we will be able to titrate patients to the most effective dose for them, based on the level that they and their doctor think is appropriate. We also believe we will be able to treat very young children at the onset of disease, and redose if needed years later. And the non-viral approach means we don’t have to exclude people with pre-existing antibodies to AAV vectors. This means more people can receive the care they need, even if they have previously been treated with an AAV gene therapy.
On a larger scale, our platform is able to be manufactured using existing biologics infrastructure – requiring significantly fewer resources than are needed to produce AAV gene therapy. Our hope is that this scalable manufacturing process will enable broader access to these potentially life-changing therapies.
I would say that the community should know that we want to partner with them, learn from them and make sure their voice is present in everything we do in the field.
As chief medical officer, what I most look forward to is learning directly from the hemophilia community – individuals, families, advocacy groups and physicians – and ensuring these perspectives inform our work.
We’ve begun these important conversations with the patient community and their insights are shaping our next generation of therapies. What we’ve learned so far is that individualization, safety and predictable, long-lasting protection are some of the most important areas of focus. We believe it’s important for patients to be able to maintain their factor VIII at the levels they feel most comfortable with to best fit their lifestyle.
Above all, safety is key – the community needs to know how seriously we take safety as well as transparency in our information about our potential therapies.
I would also highlight that we’ve made important and exciting progress toward bringing a potential therapy into the clinic. In January, we announced two milestone achievements for non-viral gene therapy: target levels of factor VIII expression in mouse models of hemophilia A and translation of expression to non-human primates. These data show us we’re on the right track. Our hope is to begin clinical trials in 2022.
We are working hard to create a future without fear of bleeds, without chronic treatment and without the shadow of the disease hanging over every family living with hemophilia. Someday in the near future, I hope to recognize Bleeding Disorders Awareness Month at a time when there are treatments available to families around the world that allow them to forget, for years on end, that they have hemophilia.
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