General Medical Sciences
DNA helices Image courtesy of the National Institute of
The European Medicines Agency (EMA) has granted AMT-060 access to the agency’s PRIority MEdicines (PRIME) program.
AMT-060 is an investigational gene therapy intended for the treatment of patients with severe hemophilia B.
The goal of the EMA’s PRIME program is to accelerate the development of therapies that may offer a major advantage over existing treatments or benefit patients with no treatment options.
Through PRIME, the EMA offers early and enhanced support to developers in order to optimize development plans and speed regulatory evaluations to potentially bring therapies to patients more quickly.
To be accepted for PRIME, a therapy must demonstrate the potential to benefit patients with unmet medical need through early clinical or nonclinical data.
About AMT-060
AMT-060 consists of a codon-optimized wild-type factor IX (FIX) gene cassette, the LP1 liver promoter, and an AAV5 viral vector manufactured by uniQure using its proprietary insect cell-based technology platform. UniQure is the company developing AMT-060.
The EMA’s decision to grant AMT-060 access to the PRIME program is based on results from an ongoing phase 1/2 study. Updated data from this study were presented at the 2016 ASH Annual Meeting (abstract 2314).
The presentation included data on 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 x 1012 gc/kg, and 5 received AMT-060 at 2 x 1013 gc/kg.
Patients in the low-dose cohort were followed for up to 52 weeks, and those in the higher-dose cohort were followed for up to 31 weeks.
Data from the higher-dose cohort showed a dose response with improvement in disease state in all 5 patients. Four patients who previously required prophylactic FIX therapy were able to stop this therapy.
As of the data cutoff date, 1 unconfirmed spontaneous bleed had been reported during an aggregate of 94 weeks of follow-up after the discontinuation of prophylaxis.
Researchers previously reported that 4 patients in the low-dose cohort were able to discontinue prophylactic therapy. The 1 patient who remained on prophylaxis sustained an improved disease phenotype and also required materially less FIX concentrate after treatment with AMT-060.
According to uniQure, all 5 patients in the low-dose cohort maintained “constant and clinically meaningful” levels of FIX activity for up to 52 weeks post-treatment. In fact, there were no spontaneous bleeds in these patients in the last 14 weeks of observation.
uniQure also said AMT-060 was well-tolerated, and there have been no severe adverse events.
Three patients (2 in the higher-dose cohort and 1 previously reported from the low-dose cohort) experienced mild, asymptomatic elevations of alanine aminotransferase and received a tapering course of corticosteroids per protocol.
These temporary alanine aminotransferase elevations were not associated with any loss of endogenous FIX activity or T-cell response to the AAV5 capsid.
None of the patients in either cohort have developed inhibitory antibodies against FIX, and none of the patients screened tested positive for anti-AAV5 antibodies.
