Rare Daily Staff

Gene therapy company uniQure said a study published in the journal Blood based clinical data from an ongoing phase 1/2 trial of its gene therapy AMT-060 in patients with severe hemophilia B suggests it provides a durable response after one year.

Hemophilia B is a rare, inherited, severe blood clotting disorder caused by a missing or defective clotting protein called Factor IX. AMT-060 consists of an adeno-associated virus serotype 5 viral vector with the wild-type variant of factor IX.

The study reports data on up to one year of follow-up from the low-dose cohort of patients in the trial and up to six months of follow-up on patients in the higher-dose cohort. It showed that following a single infusion of AMT-060, mean factor IX activity increased to 6.9 percent of normal, annualized factor IX use decreased by 73 percent. Mean annual bleeding rate declined by 70 percent for patients in the higher-dose cohort. The study was based on data from ten adults with hemophilia B and severe-bleeding phenotype.

The study showed that AAV5 liver-directed wildtype hfactor IX gene transfer was well tolerated and clinically effective in patients with severe and moderate-severe hemophilia B.  No cellular immune responses to the AAV5 vector were detected and factor IX expression levels were stable over the entire observation period. The manuscript is available online today and will be included in a future print edition of Blood.

uniQure is preparing to initiate a pivotal study in 2018 with AMT-061, which combines an AAV5 vector with the FIX-Padua mutant. AMT-061 and AMT-060 are identical in structure apart from two nucleotide substitutions in the coding sequence for factor IX. The gene variant, referred to as FIX-Padua, has been reported in multiple preclinical and nonclinical studies to provide an approximate 8- to 9-fold increase in factor IX clotting activity compared to the wild-type factor IX gene. 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.

December 18, 2017