Gene therapy increases factor IX activity in severe hemophilia B

The investigational gene therapy AMT-061 showed increases in factor IX activity sustained at 25% to 51% of normal among patients with severe or moderately severe hemophilia B, according to updated clinical data reported by the manufacturer.

AMT-061 (uniQure) consists of an AAV5 viral vector carrying a gene cassette with the Padua variant of factor IX, which induced an eight- to ninefold increase in factor IX activity compared with the wild-type factor IX protein used in an earlier version of the gene therapy, AMT-060.

The ongoing phase 2b study of AMT-061 — updated data from which were presented at Annual Congress of the European Association for Haemophilia and Allied Disorders — enrolled three patients with severe hemophilia who received a single IV infusion of 2x1013 vc/kg.

All patients had low levels of pre-existing antibodies to AAV5 prior to treatment, and two patients had previously been excluded from another gene therapy study due to antibodies for a different AAV vector.

Results showed all patients experienced increasing and sustained factor IX levels — measured using an activated partial thromboplastin time assay — with mean factor IX activity increased to 38% of normal at 12 weeks, which exceeds the threshold levels considered sufficient to eliminate or significantly reduce the risk for bleeding.

Factor IX activity reached 48% of normal at 16 weeks in the first patient, 25% of normal at 14 weeks in the second patient, and 51% of normal at 12 weeks in the third patient.

“We are extremely pleased with these updated data,” Robert Gut, MD, PhD, chief medical officer of uniQure, said in a press release. “The study demonstrates AMT-061 has the potential to increase factor IX activity into the normal range and continues to be very well-tolerated, with no serious adverse events reported and no patients requiring any immunosuppression therapy. We look forward to providing further updates on these patients later in the year at other academic conferences.”

No patient in the study experienced a material loss of factor IX activity, reported any bleeding events or required any infusions of factor IX replacement therapy.

One patient experienced aspartate aminotransferase elevation, which resolved without additional treatment or loss of factor IX activity.

“Our goal with AMT-061 is to give all people living with hemophilia B access to a one-time treatment capable of normalizing factor IX activity and eliminating the need for replacement therapy, without the risk [for] immune responses that require immunosuppression or may lead to a loss of efficacy,” Matt Kapusta, CEO of uniQure, said in the release. “These updated data continue to suggest that AMT-061 may be the first gene therapy able to achieve this goal, and we remain focused on completing enrollment in our ongoing pivotal phase 3 study by the end of the year.”

Researchers will continue to follow these patients for 52 weeks to assess factor IX activity, bleeding rates and usage of factor IX replacement therapy, and for 5 years to evaluate the safety of AMT-061.

The investigational gene therapy AMT-061 showed increases in factor IX activity sustained at 25% to 51% of normal among patients with severe or moderately severe hemophilia B, according to updated clinical data reported by the manufacturer.

AMT-061 (uniQure) consists of an AAV5 viral vector carrying a gene cassette with the Padua variant of factor IX, which induced an eight- to ninefold increase in factor IX activity compared with the wild-type factor IX protein used in an earlier version of the gene therapy, AMT-060.

The ongoing phase 2b study of AMT-061 — updated data from which were presented at Annual Congress of the European Association for Haemophilia and Allied Disorders — enrolled three patients with severe hemophilia who received a single IV infusion of 2x1013 vc/kg.

All patients had low levels of pre-existing antibodies to AAV5 prior to treatment, and two patients had previously been excluded from another gene therapy study due to antibodies for a different AAV vector.

Results showed all patients experienced increasing and sustained factor IX levels — measured using an activated partial thromboplastin time assay — with mean factor IX activity increased to 38% of normal at 12 weeks, which exceeds the threshold levels considered sufficient to eliminate or significantly reduce the risk for bleeding.

Factor IX activity reached 48% of normal at 16 weeks in the first patient, 25% of normal at 14 weeks in the second patient, and 51% of normal at 12 weeks in the third patient.

“We are extremely pleased with these updated data,” Robert Gut, MD, PhD, chief medical officer of uniQure, said in a press release. “The study demonstrates AMT-061 has the potential to increase factor IX activity into the normal range and continues to be very well-tolerated, with no serious adverse events reported and no patients requiring any immunosuppression therapy. We look forward to providing further updates on these patients later in the year at other academic conferences.”

No patient in the study experienced a material loss of factor IX activity, reported any bleeding events or required any infusions of factor IX replacement therapy.

One patient experienced aspartate aminotransferase elevation, which resolved without additional treatment or loss of factor IX activity.

“Our goal with AMT-061 is to give all people living with hemophilia B access to a one-time treatment capable of normalizing factor IX activity and eliminating the need for replacement therapy, without the risk [for] immune responses that require immunosuppression or may lead to a loss of efficacy,” Matt Kapusta, CEO of uniQure, said in the release. “These updated data continue to suggest that AMT-061 may be the first gene therapy able to achieve this goal, and we remain focused on completing enrollment in our ongoing pivotal phase 3 study by the end of the year.”

Researchers will continue to follow these patients for 52 weeks to assess factor IX activity, bleeding rates and usage of factor IX replacement therapy, and for 5 years to evaluate the safety of AMT-061.