uniQure Announces New Preclinical Data in Hemophilia A and Fabry Disease in Oral Presentations at the 22nd ASGCT Annual Meeting
LEXINGTON, Mass. and AMSTERDAM, the Netherlands, May 02, 2019 (GLOBE NEWSWIRE) -- uniQure N.V. (NASDAQ: QURE), a leading gene therapy company advancing transformative therapies for patients with severe medical needs, will present today new preclinical data on its gene therapy candidates AMT-180 for the treatment of hemophilia A and AMT-190 for the treatment of Fabry disease. These data will be featured today in back-to-back oral presentations at the 22nd American Society for Gene and Cell Therapy (ASGCT) Annual Meeting in Washington D.C.
AMT-180 for Hemophilia A
Hemophilia A is an X-linked bleeding disorder resulting from a deficiency in coagulation Factor VIII that serves as a cofactor for Factor IX in the activation of the coagulation cascade. About 30 percent of the hemophilia A patient population develops inhibitors to Factor VIII over the course of the disease.
AMT-180 comprises a recombinant AAV5 vector incorporating a proprietary modified Factor IX hat, when activated through normal mechanisms, induces thrombin generation independently of Factor VIII.
Data from multiple in vitro and in vivo studies show that a single intravenous administration of AMT-180 results in dose-dependent, therapeutically meaningful Factor VIII-independent activity as measured by thrombin generation and one-stage clotting assay. AMT-180 is a differentiated approach that is suggested to be hepatocyte-friendly and non-thrombogenic based on the studies conducted to date and is expected to reduce and potentially prevent bleedings in hemophilia A patients with and without inhibitors.
AMT-180 Preclinical Data Findings
Proof-of-concept for AMT-180 was established through studies across two different animal models. The oral presentation at ASGCT features the following data:
Preclinical studies in FVIII-depleted human plasma show that AMT-180 induced clinically relevant thrombin activation, and up to 29% of Factor VIII-independent activity, in plasma with and without inhibitors.
The mechanistic proof-of-concept of AMT-180 was demonstrated in a hemophilia A mouse model, where a single intravenous administration of AMT-180 resulted in sustained, dose-dependent hemostatic effect as measured by one-stage clotting assay.
The studies further demonstrate that AMT-180 shows activation kinetics similar to native FIX and is not hyperactive.
A pilot study in non-human primates demonstrated that a single administration of AMT-180 resulted in sufficient FIX protein expression that translates to clinically relevant Factor VIII-independent activity in humans. No elevation of coagulation activation markers or signs of thrombi formation were observed.
“Data from these preclinical studies show the exciting potential of AMT-180 to provide clinically meaningful Factor VIII-independent activity after a one-time administration.” stated Sander van Deventer, M.D., Ph.D., chief scientific officer at uniQure. “We are particularly encouraged by the broad potential of AMT-180 in treating both patients with and without inhibitors, and the unique approach of AMT-180 that potentially circumvents durability issues because of its hepatocyte-friendly profile.”