UniQure CEO Speaks AMT-061 at J.P. Morgan


At the 36th Annual J.P. Morgan Healthcare Conference, uniQure announced that in 2018, the company intends to advance its gene therapy AMT-061 into a pivotal study for hemophilia B.

At the 36th Annual J.P. Morgan Healthcare Conference, uniQure announced that in 2018, the company intends to advance its gene therapy AMT-061 into a pivotal study for hemophilia B.

Patients with the rare genetic disorder hemophilia B have reduced factor IX activity, which significantly reduces the blood’s ability to properly clot. As a result, people with the condition risk excessive, recurrent, and potentially life-threatening bleeding episodes from even the most minor injuries.

The company has plans to initiate a global, pivotal program for the drug during the third quarter of 2018, and top-line data from the patients in the dose-confirmation study are expected to be announced before the end of the year. uniQure has achieved alignment with the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) on expedited and clinical regulatory pathway for AMT-061, a potential best-in-class gene therapy that combines Factor IX (FIX)-Padua gene with adeno-associated virus 5 (AAV5).

At the 59th American Society of Hematology (ASH) Meeting and Exposition in Atlanta last month, uniQure presented data exhibiting the drug’s ability to increase FIX activity in non-human primates with AMT-061 6-to-7 times as effectively as AMT-060, a previous version of the same compound. With these results, the drug was granted Breakthrough and PRIME designations from the FDA and EMA, respectively.

Rare Disease Report (RDR) sat down with Matthew Kapusta, uniQure’s CEO, to discuss AMT-061, the excitement surrounding it, and what he expects to see from the drug in 2018.

RDR: What’s the background of AMT-061? How long has it been in development?

Kapusta: We’ve been developing, for a number of years, a gene therapy targeting hemophilia B, and we have one that is an AAV5-delivering Padua-FIX construct. It is administered through a simple IV infusion that is typically infused over 30 minutes, and ultimately, I think the vision is that, commercially, this will be a fairly simple outpatient procedure. We did a Phase 1/2 study on the first generation of the product that was using the wild-type gene cassette, and at the most recent ASH meeting in December, we presented 2-year follow-up data that showed a dramatic clinical effect on the patients. What we decided to do last year, though, was to make a slight modification to the trans gene that increases the potency of the Factor IX protein that is actually produced and we demonstrated that this slight modification will increase the clotting activity of each protein molecule by about 6-8 times.

RDR: What were the driving forces behind the update to the compound?

Kapusta: One of the things that we were hearing from the key opinion leaders was that they wanted to see higher levels of Factor IX activity, and curative levels of Factor IX are generally considered to be above 40-50%. With this new potency change, we think we can get patients into the 30-50% range of normal Factor IX activity level, so near curative levels. At those levels, the expectation is that patients will no longer require Factor IX replacement therapy, and that there will be a near cessation of bleeding. The potential that the long-term prognosis of their joint health will be significantly benefitted. It’s really, really exciting stuff. The data that we presented at ASH in December showed remarkably durable levels of Factor IX activity up to 2 years post-treatment. The patients, really, were not bleeding, and if you look at the presentation, you’ll see actual images of the patients who were in the study. We’ve met these patients and their lives have been remarkably transformed. We’re taking this construct into a pivotal study. We expect to initiate this study in the third quarter of this year. The pivotal study will include approximately 40 patients who will serve as their own control. We will be administering the gene therapy to these patients and then following them up for about 52 weeks. We think that this single registration study will provide sufficient enough evidence for us to submit a BLA (Biologics License Application).

RDR: How have people within the hemophilia community been reacting to the potential of AMT-061?

Kapusta: The reception has been really very exciting. There’s been a lot of media coverage, and the hemophilia community, not unlike a lot of these other rare and orphan disease communities, are very tight-knit. There’s been a growing level of excitement about gene therapy. I think, initially, there might have been some pretty reasonable anxiety about what to expect as it pertained to safety and how long the treatment would last, but the first gene therapy clinical studies were done more than 8 years ago. All of the clinical work that has been done in hemophilia — and there have been multiple studies conducted – have shown well-tolerated, highly safe gene therapy with the ability to have a dramatic impact on the lives of patients.

I think there’s a growing level of excitement. This is a patient population that has become increasingly cautious over the years, and they have gotten used to taking replacement therapy. If you think about what is happening to these patients, some hemophiliacs are taking 3+ infusions per week, and if you multiply that out, you’re talking about 150-200 infusions per year for the rest of their lives. The mere thought of being able to take a 30-minute IV infusion that eliminates the need to do that, and not only eliminate the need to do it, but that it might completely eliminate the propensity for bleeding, it’s pretty remarkable. Even the payers are getting greater appreciation and excitement for it. Not only is it 150-200 infusions per year, but the cost of this could be $300,000-500,000 per patient per year for the rest of their lives. It’s really millions of dollars per patient, and the potential to have a one-time curative therapy is very exciting even to the payers. We’re very pleased to be in the middle of this, and in a position to begin a registrational study. We’re excited to potentially be first-to-market with a transformative therapy.

RDR: What kinds of milestones is uniQure hoping to hit in 2018?

Kapusta: We have a number of important milestones. I would say that the key ones are we expect to file our IND (investigational new drug) application with the FDA this quarter. We expect to initiate the treatment of patients in our program in the third quarter of this year. We expect to release data from those initial patients before the end of the year. Those are the key milestones on the hemophilia B program.

RDR: There are a lot of other players in the gene therapy space. What makes uniQure stand out?

Kapusta: One of the most critical things about bringing the gene therapies to market successfully is going to be the ability to manufacture these products. One of the differentiator points for UniQure is that we’ve been in the field of gene therapy for more than 20 years, and we’ve spent more than 10 years refining and optimizing our manufacturing capabilities. There aren’t many other players in the gene therapy space that can boast like that.

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