uniQure recently announced new data from its phase 3 HOPE-B trial of etranacogene dezaparvovec, the company’s investigational gene therapy candidate for patients with severe and moderately severe hemophilia B. The therapy consists of an adeno-associated virus serotype 5 (AAV5), which has been demonstrated to be a safe and well-tolerated vector carrying a gene cassette with the Padua variant of factor IX (FIX). AAV5 is a variant of the type of the adeno-associated virus (AAVs) vectors that are being investigated in multiple gene therapy trials.

The data encompassed all 54 patients who have so far received a single administration of etranacogene dezaparvovec. Notably, patients were not excluded from the trial based on pre-existing neutralizing antibodies to AAV5. According to a uniQure press release, factor IX (FIX) activity in all 54 participants “increased rapidly” after dosing, from less than 2% to a mean of 37.2% at 26 weeks. During this 26-week post dose period 72% of patients (39/54) reported no bleeding events, while 15 participants reported a total of 21 bleeds. In addition, mean annualized usage of FIX replacement therapy declined by 96%. The therapy was also generally well-tolerated with no treatment-related serious adverse events.

 “We are extremely pleased that these top-line pivotal data show that a single administration of etranacogene dezaparvovec gene therapy led to sustained increases of Factor IX (FIX) to functionally-curative levels capable of eliminating the need for regular infusions to control and prevent bleeding episodes,” said Ricardo Dolmetsch, PhD, president of research and development at uniQure. “Most impressively, these data also demonstrate the potential to achieve clinical benefit in patients with a range of pre-existing neutralizing antibodies representative of the general population. The ability to dose a gene therapy in patients with pre-existing neutralizing antibodies has not been demonstrated for any other gene therapy and illustrates the potentially unique ability of our AAV5 platform to address the needs of a broad set of patients living with hemophilia B and other disorders.”

These data were published as a late-breaking abstract for oral presentation at the upcoming 62nd Annual Meeting of the American Society of Hematology on December 8th.

Source: uniQure press release dated November 19, 2020