Gene Therapy for Hemophilia: ARM Studios Interview with Matthew Kapusta

Excellent, thanks for having me here.

Yeah, so I'm really proud to talk about Uniqure. Uniqure is one of the first pioneers within gene therapy. The company was founded in 1998, so it's over a quarter of a century years old, and we're really proud of the fact that Uniqure was able to get two approved gene therapies. One included a product called Glybera, which is the first gene therapy approved in the Western world. That was a product for a very ultra-orphan indication called lipoprotein lipase deficiency, which is a metabolic disorder. That product was approved in Europe under exceptional circumstances in 2012. That was kind of the first chapter of Uniqure. And then the second chapter of Uniqure, which covered or spanned about 10 to 15 years, was getting our second approved gene therapy, a product called Hemgenix, which is the first gene therapy for the treatment of Hemophilia B. So that was approved a couple years ago and is currently on the market in the United States and Europe and other countries. And then now we're really focused on expanding our pipeline beyond hemophilia and some of those earlier indications. We have a lead program in Huntington's disease, which we're very excited about. It really has the potential to be best and first in class, and that study was started about 5 years ago, so we're really developing a really robust data package. We have three other clinical studies: one in ALS, the other one in epilepsy, and the last one in Fabry disease. We have a number of research activities that are focused on liver-directed disorders and CNS diseases. Our company has approximately 175 people, most of that is in the Netherlands where the company was founded, and I'm based with a number of other people in clinical operations and regulatory affairs in Lexington, Massachusetts.

Yeah, I mean, I will tell you, this is such a personal crowning achievement, Hemgenix, firstly for the patients, but also for me personally, for all of our employees, the clinicians that were involved, our investigators, and the scientists. For any drug that is approved, let alone a very complicated gene therapy, it's a labor of love that takes, in our case, 10 to 15 years and a lot of eating glass and running through walls. And we're just extremely proud of actually getting this product over the finish line. The product, as you mentioned, is partnered with CSL Behring. They are our commercial partner globally. And the product is now being offered to 10 to 15,000 patients with hemophilia B across Europe and the United States and expanding beyond that. I think one of the things that I appreciate the most about this opportunity is that hemophilia was probably one of the first indications that was explored by gene therapy, and so it was a little bit of waiting for GDAU. There was a lot of transformational potential that was talked about for probably 15 years, and so finally we're in a position where we can offer this therapy to patients, which effectively allows them... It really continues a number of trends that have been happening for a long time. So hemophilia patients are really trying to get... they have peaks and troughs because there's a very short half-life of replacement therapy, right? So the existing therapies are infused. Severe hemophiliacs will take them sometimes two, three times a week. Even after a few days, the level of Factor 9, which is their clotting factor, will decline, and in some cases declines below a level where breakthrough bleeds can happen. So what hemophilia patients want is they want trough levels that are as high as possible to eliminate breakthrough bleeds, and they want to take infusions as less frequently as possible. So a gene therapy provides constant Factor 9 expression over time, and it's theoretically one and done. And we did our clinical development across three different clinical studies in about 70 patients. I think CSL Behring just presented, I want to say, close to 5 years of follow-up on some of the earliest patients that were treated, and they have remarkable durability. There's a greater than 90% reduction in the amount of infusions that they're doing, and I think nearly all of them continue to be off of prophylactic replacement therapy. So it's just a phenomenal, transformative therapy that we finally have delivered to these patients after all these years, and we're just really excited to be part of that story.

Oh yeah, I've met a lot of patients with hemophilia in my years. I've gone to dinner with these patients, we've had them speak to employees. They really tell us that they feel like they have their life back again. They tell us that they previously had problems being active, they had problems holding down jobs, and they talked about how they feel like they have been freed from their disease burden now that they had the opportunity to take a gene therapy. So it's obviously a disorder where there's existing treatments available, right? But it's not just a convenience play. I mean, I've got to make that very clear. It's not just, 'Oh well, I've taken this because now I don't have to do any more infusions again.' They really feel freed from the burden of their disease, and that's giving them back their life, which is great.

No, they are very expensive. I mean, we've done some healthcare economic analysis on Hemgenix where the average cost of a patient that has severe hemophilia B over the course of their life could be upwards of $20 million. So not only are they expensive, you can have annual replacement therapy that can be 5, 600,000 a year. But again, it's not just the health economic argument. I think that's great for payers. The fact is that there's more and more evidence that shows that this therapy is not only more convenient and durable, but it actually is superior in terms of preventing bleed and providing hemostatic control, right? So it really provides a lot of value to multiple stakeholders throughout the continuum.

So right now, I mean, my life is really focused on work, as you probably know. But beyond that, I've got three kids. The oldest is a sophomore in college, my middle one is a senior in high school, my youngest one is a sophomore in high school. Everything outside of work is really revolving around those three kids. And then I've got three dogs and a cat. So we've got very busy. My wife and I play a ton of pickleball. We're really into that. It's not just an old person sport. And we just try to stay as healthy as we can and try to have fun.

Of course. Thanks. Pleasure.