Rare Daily Staff

Dutch biotech UniQure reported updated clinical data in patients treated in the company’s ongoing phase 2b study of AMT-061, its investigational gene therapy for the treatment of patients with severe and moderately severe hemophilia B.

The data, presented at the Hemostasis & Thrombosis Research Society 2019 Scientific Symposium, showed that clinically significant elevations of factor IX activity continued to be sustained in all three patients in the study up to six months after a single administration of the gene therapy.

Hemophilia B is a hereditary bleeding disorder caused by a lack of blood clotting factor IX (FIX), which results in blood that cannot clot properly to control bleeding.

The phase 2b study of AMT-061 is an open-label, single-dose, single-arm, multi-center trial being conducted in the United States. Three patients with severe hemophilia (endogenous FIX activity less than one percent) were enrolled in the study and received a single intravenous infusion of the AAV5 gene therapy. Prior to the administration, all three patients showed low levels of pre-existing neutralizing antibodies to AAV5 but were not excluded from the trial on that basis. Patients will be followed for 52 weeks to assess FIX activity, bleeding rates and usage of FIX replacement therapy, and will be monitored for five years to evaluate the safety of AMT-061.

AMT-061 consists of an AAV5 viral vector carrying a gene cassette with the patent-protected Padua variant of Factor IX (FIX-Padua). AMT-061 has been granted Breakthrough Therapy Designation by the United States Food and Drug Administration (FDA) and access to the Priority Medicine (PRIME) regulatory initiative by the European Medicines Agency.

The interim data shows that all three patients have demonstrated increasing and sustained FIX levels after the one-time administration of AMT-061, with two of the three patients now achieving FIX activity in the normal range. Mean FIX activity for the three patients at six months after administration increased to 47 percent of normal. The first patient achieved FIX activity of 51 percent of normal, the second patient achieved FIX activity of 33 percent of normal, and the third patient achieved FIX activity of 57 percent of normal. The second and third patients had previously screen-failed and were excluded from another gene therapy study due to pre-existing neutralizing antibodies to a different AAV vector. Reported FIX activity was measured using an activated partial thromboplastin time assay performed at a central laboratory.

“We believe these to be striking clinical data that show AMT-061 has the potential to deliver consistent and sustained increases in Factor IX activity into the range considered normal,” said Robert Gut, chief medical officer of UniQure. “Importantly, results across all patients in this study, even those that previously screen-failed other gene therapy studies, show no loss of FIX activity, no bleeding events and no need for infusions of FIX replacement therapy through six months after administration.” 

UniQure is currently enrolling patients in a pivotal trial of AMT-061, a multinational, multi-center, open-label, single-arm study to evaluate its safety and efficacy. Approximately 50 adult hemophilia B patients classified as severe or moderately severe will be enrolled in a six-month observational period during which time they will continue to use their current standard of care to establish a baseline control. After the six-month lead-in period, patients will receive a single intravenous administration of AMT-061. Dosing of patients in the pivotal trial is now underway.

The primary endpoint of the study will be based on the FIX activity level achieved following the administration of AMT-061, and the secondary endpoints will measure annualized FIX replacement therapy usage, annualized bleed rates and safety.

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

Photo: Robert Gut, chief medical officer of UniQure

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