Gene Therapy:

Hemophilia

uniQure has built a best-in-class hemophilia B gene therapy program.

uniQure has built an exciting clinical program focused on hemophilia B, a severe orphan blood clotting disorder. Our gene therapy product candidate AMT-061 consists of an AAV5 viral vector carrying a gene cassette with the Padua variant of Factor IX (FIX-Padua).  uniQure plans to expeditiously advance AMT-061 into a pivotal study in 2018 for patients with severe and moderately severe hemophilia B.

Our mission in hemophilia B is to develop the safest and most effective gene therapy with the broadest application to patients. We believe AMT-061 has the potential to be an important gene therapy for patients suffering with hemophilia B.  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 (view press release).

AMT-061 and AMT-060, the latter of which has been tested in 10 patients in an ongoing Phase I/II study, are identical gene therapies apart from two nucleotide substitutions in the coding sequence for FIX.  The gene variant, referred to as FIX-Padua, has been reported to provide an approximate 8 to 9-fold increase in FIX activity compared to the wild-type FIX protein used in AMT-060. All other critical quality attributes of AMT-061 are expected to be comparable to those of AMT-060, as AMT-061 utilizes the same AAV5 capsid and proprietary insect cell-based manufacturing platform. 

uniQure’s AAV5-based gene therapies have been demonstrated to be generally safe and well-tolerated in three uniQure trials conducted in 22 patients in hemophilia B and other indications.  In contrast to data reported using other AAV capsids, no patient treated in clinical trials with our AAV5 gene therapies has experienced any confirmed, T-cell-mediated immune response to the capsid or material loss of FIX activity.   

In January 2017, AMT-060 received Breakthrough Therapy designation from the U.S. Food and Drug Administration in January 2017 based on results from our Phase I/II study (view press release).  In April 2017, our hemophilia B gene therapy also received PRIME designation by the European Medicines Agency (EMA).  The FDA and EMA have agreed that AMT-061 will be included under the existing Breakthrough Therapy and PRIME designations, respectively.  

In July 2017, the Company presented updated clinical data from our Phase I/II trial (view press release).   

The data from our Phase I/II study demonstrate that our AAV5-based gene therapy has been safe, effective and durable, with no loss of efficacy at up to 18 months of observation and no cellular immune responses in any patient. 

Our hemophilia B gene therapy has demonstrated a very low screening failure rate, and we have presented clinical data demonstrating that the presence of pre-existing anti-AAV5 neutralizing antibodies (NABs) does not predict the potential efficacy of AAV5-mediated gene transfer in patients with hemophilia B (view press release).  This development potentially expands the applicability of AAV5 gene therapies to all, or nearly all hemophilia B patients. 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 AMT-061 from other hemophilia gene therapies in development, and we look forward to advancing our program into a pivotal Phase III clinical study in 2018.

 

Hemophilia A

The Company is in pre-clinical evaluation for a gene therapy to treat hemophilia A.