Rare Disease Report

Hemophilia B and Gene Therapy 9 Month Data Promising

JULY 28, 2016
James Radke, PhD
Plenty of exciting data is coming out of this year’s World Federation of Hemophilia (WFH) 2016 World Congress in Orlando, FL, including the use of gene therapy to treat hemophilia B. Today, uniQure provided an update on their ongoing gene therapy study in patients with severe hemophilia B.

Phase I/II Study with Gene Therapy

In the Phase I/II, open-label, multi-center study, 10 patients received a one-time, 30-minute, intravenous administration of AMT-060, a gene therapy that consists of a codon-optimized wild type FIX gene cassette, the LP1 liver promoter and an AAV5 viral vector. Five of the patients received receiving 5x1012 gc/kg and 5 received 2x1013 gc/kg. At the WHF Congress, 9 month data from the first 5 receiving the lower dose was presented.

Prior to the study, all 5 had severe or moderate to severe hemophilia and were on prophylactic FIX therapy. After 9 months, only 1 remained on prophylactic therapy. Of the remaining 4 who had discontinued FIX therapy, the mean steady-state FIX activity was 5.4% of normal, with a range from 3.1% to 6.7% of normal.  Furthermore, in those 4 patients total FIX usage dropped 82%. For the 1 patient who remained on prophylactic therapy, they required ‘materially less FIX concentrate’ after treatment with AMT-060.
AMT-060 was well tolerated. One patient experienced a mild, transient and asymptomatic elevation of alanine aminotransferase (ALT) 10 weeks after treatment. No cellular immune response to AAV5 was evident.
In a press release, Wolfgang Miesbach, MD, professor of hematology at the University of Frankfurt, Germany stated, "I am very encouraged by the stability of increased FIX activity of AMT-060 and the significant reduction in required infusions of factor replacement.” Dr Miesbach added,"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.”

 9 Month Data Summary

Below is the data available on the 5 patients that the company included in a press release.

*Patients 3 and 5 are siblings.
**Based on FIX activity using guidelines as published in Thromb Haemost 2001; 85: 560.
***Steady-state FIX activity was defined as the mean of all levels measured after the discontinuation of prophylactic FIX infusions through the most recent follow-up assessment, with the latter measurement performed at least 10 days after the most recent administration of Factor IX concentrate.

What is Hemophilia B?

Hemophilia B is a genetic disorder caused by missing or defective factor IX, a clotting protein. Although it is passed down from parents to children, about 1/3 of cases are caused by a spontaneous mutation, a change in a gene.
Current standard of care for patients with hemophilia B involves chronic replacement of FIX protein through intravenous infusion. In 2013, the World Federation of Hemophilia estimated there were more than 28,000 hemophilia B patients worldwide, including 4,000 patients in the United States.

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