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Image courtesy of NIGMS

ORLANDO—The gene therapy AMT-060 can reduce the need for factor IX (FIX) prophylaxis in patients with severe hemophilia B, results of a phase 1/2 study suggest.

All of the patients treated in the low-dose cohort of this study have had sustained improvements in their disease phenotype and continue to maintain durable levels of FIX gene activity for up to 39 weeks post-treatment.

Four of the 5 patients were able to discontinue prophylactic FIX infusions.

In addition, AMT-060 was considered well-tolerated. There were 2 serious adverse events, but both were temporary. And none of the patients developed FIX inhibitors.

These data were presented at the World Federation of Hemophilia 2016 World Congress.* The research is sponsored by uniQure.

“I am very encouraged by the stability of increased FIX activity of AMT-060 and the significant reduction in required infusions of factor replacement,” said study investigator Wolfgang Miesbach, MD, of the University of Frankfurt in Germany.

“This effect is particularly important because it is seen in severe patients with established joint disease who experienced a high frequency of joint bleeds despite intense use of prophylactic FIX prior to study entry.”

Patients and treatment

AMT-060 consists of a codon-optimized wild-type FIX gene cassette, the LP1 liver promoter, and an AAV5 viral vector manufactured by uniQure using its proprietary insect cell-based technology platform.

In this phase 1/2 trial, Dr Miesbach and his colleagues are testing AMT-060 in 10 patients. All patients had severe or moderately severe hemophilia at baseline, including documented FIX levels less than 1% to 2% of normal, and required chronic infusions of prophylactic or on-demand FIX therapy at the time of enrollment.

Each patient received a 1-time, 30-minute, intravenous dose of AMT-060, without the use of corticosteroids. Five patients received AMT-060 at 5×1012 gc/kg, and 5 received AMT-060 at 2×1013 gc/kg.

Dr Miesbach presented results observed in the low-dose cohort. Patients in the high-dose cohort are still in the early stages of follow-up.

Most patients in the low-dose cohort were older than 50 years of age (range, 35-72). Four patients had severe hemophilia B, and 4 had advanced joint disease. All of the patients had frequent bleeding episodes, despite receiving once- or twice-weekly FIX prophylaxis.


For all 5 patients in the low-dose cohort, the mean annualized total FIX usage declined 75% after treatment with AMT-060.

“The majority of patients in this low-dose cohort of AMT-060 are showing FIX activity in the range of 5% of normal, and clinical experience has shown that patients in this range generally do not require prophylactic factor replacement and have a very low frequency of spontaneous joint bleeding episodes,” Dr Miesbach said.

Four patients discontinued prophylactic therapy. The 1 patient who remained on prophylactic therapy has sustained an improved disease phenotype and also required materially less FIX concentrate after treatment with AMT-060.

Through up to 9 months of follow-up, the mean steady-state FIX activity for the 4 patients who discontinued prophylactic FIX therapy was 5.4% of normal, with a range from 3.1% to 6.7% of normal.  These patients had a mean reduction in annualized total FIX usage of 82%.

Safety and immunogenicity

Two patients experienced serious adverse events. One patient had self-limiting fever in the first 24 hours after receiving AMT-060.

The other patient had a transient elevation of alanine aminotransferase (ALT) that was responsive to tapering prednisolone (60 mg/day start dose) without loss of FIX activity. At baseline, this patient’s ALT was 26 IU/L. It hit a peak of 61 IU/L at week 10, but values returned to baseline levels within 2 weeks of treatment.

As expected, all of the patients developed anti-AAV5 antibodies after week 1. None of the patients developed inhibitory antibodies against FIX.

There was no evidence of sustained AAV5 capsid-specific T-cell activation, although 1 patient had transient T-cell activation slightly above the positive threshold at 1 time point. This patient did not have ALT elevation. end hematology article

*Miesbach W et al, Updated results from a dose escalating study in adult patients with haemophilia B treated with AMT-060 (AAV5-hFIX) gene therapy, WFH 2016 World
Congress, July 2016

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