Gene Therapy:


uniQure has built a potential first- and best-in-class hemophilia gene therapy program.

Hemophilia B

uniQure is advancing a promising clinical program focused on hemophilia B, a severe orphan blood clotting disorder. Our gene therapy product candidate etranacogene dezaparvovec (AMT-061) consists of an AAV5 viral vector carrying a gene cassette with the Padua variant of Factor IX (FIX-Padua). 

uniQure is now conducting the Phase III HOPE-B pivotal study of etranacogene dezaparvovec for the treatment of patients with severe and moderately severe hemophilia B. In February 2019, we announced that we've treated the first patient in the trial, and in September 2019 we announced that the planned enrollment of 56 patients has been achieved. Due to the high level of interest in the study from both patients and study investigators, uniQure expects to over-enroll up to six additional patients before the end of September. 

Our goal in hemophilia B is to develop the safest and most effective gene therapy with the broadest application to patients. We believe that etranacogene dezaparvovec (AMT-061) may be the first gene therapy to provide durable, curative benefits to nearly all patients with hemophilia B, with optimized clinical and safety benefits.

Etranacogene dezaparvovec consists of an AAV5 viral vector carrying a gene cassette with the patent-protected Padua variant of Factor IX (FIX-Padua). uniQure holds multiple issued patents in the United States and Canada broadly, with patent pending in the EU, covering methods of treating bleeding disorders, including hemophilia B, using AAV gene therapy with the FIX-Padua variant. 

In July 2019, uniQure announced updated clinical data in patients treated in our Phase IIb dose-confirmation study of etranacogene dezaparvovec (view press release). These data showed that therapeutic levels of Factor IX (FIX) activity have been sustained in all patients up to nine months after a single administration -- with increases in FIX activity of up to 54% of normal and a mean of 45%. This exceeds the levels considered sufficient to eliminate or significantly reduce the risk of bleeding events, and two of the three patients are achieving FIX activity in the normal range.  

Etranacogene dezaparvovec has been granted Breakthrough Therapy Designation by the U.S. Food and Drug Administration and access to the Priority Medicines (PRIME) regulatory initiative by the European Medicines Agency. 

AAV5-based gene therapies have been demonstrated to be safe and well-tolerated in a multitude of clinical trials, including four uniQure trials conducted in 25 patients in hemophilia B and other indications. In contrast to data reported using other AAV capsids, no patient treated in clinical trials with uniQure's AAV5 gene therapies has experienced any cytotoxic T-cell-mediated immune response to the capsid. 

Additionally, our hemophilia B gene therapy provides the opportunity for all, or nearly all, hemophilia B patients to be eligible for gene transfer with etranacogene dezaparvovec. Preclinical and clinical data show that AAV5-based gene therapies may be clinically effective in patients with pre-existing antibodies to AAV5, thereby potentially increasing patient eligibility for treatment compared to other gene therapy product candidates. 

We have presented clinical data demonstrating that the presence of pre-existing anti-AAV5 neutralizing antibodies does not predict the potential efficacy of AAV5-mediated gene transfer in patients with hemophilia B (view press release) and that AAV5 gene therapies may be viable treatments for at least 97% of patients (view press release).  We believe these factors contribute to making AAV5 a potential best-in-class vector for delivering gene therapies more effectively and safely to a greater portion of patients in need of treatment.

These factors, along with our commercial-scale manufacturing capabilities, differentiate etranacogene dezaparvovec from other hemophilia gene therapies in development.


Hemophilia A

Our product candidate AMT-180 is a novel hemophilia A gene therapy that has the potential to treat all hemophilia A patients, including those with past and current inhibitors.  Approximately 30 percent of patients with severe hemophilia A will develop an inhibitor that neutralizes the infused Factor VIII (FVIII) activity. This patient population has in the past been excluded from gene therapy approaches in clinical development.

AMT-180 is a one-time, intravenously-administered, AAV5-based gene therapy incorporating a proprietary modified Factor IX gene, Super9™, that has been demonstrated in preclinical studies to circumvent inhibitors to FVIII.  A proof-of-concept study demonstrated that administration of Super9 resulted in clinically relevant FVIII mimetic activity in hemophilia A mice and was not associated with hypercoagulability in wild-type mice.   Another study in non-human primates demonstrated that a single dose of AMT-180 resulted in expression levels that translate into FVIII mimetic activity expected to be clinically relevant in hemophilia A patients with or without inhibitors. In addition, Super9 induced clinically relevant thrombin activation in FVIII-depleted human plasma with or without inhibitors.  These data show that AMT-180 may lead to durable expression in hemophilia A patients and may provide long-term prevention of bleeds.


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