uniQure N.V., a leading pharmaceutical specialized in human gene therapy, has presented additional data from its clinical trial in hemophilia B patients at the 21st Congress of the European Hematology Association (EHA), June 9-12, in Copenhagen.
The Phase 1/2 clinical trial of AMT-060 titled “Trial of AAV5-hFIX in Severe or Moderately Severe Hemophilia B,” is estimated for completion by December 2020.
According to uniQure’s CEO Daniel Soland, AMT-060 “is the only hemophilia gene therapy that combines a gene cassette with clinically proven multi-year durability and an AAV5 vector serotype that has demonstrated safety and broad applicability in more than 25 patients across three clinical studies.”
Hemophilia B is a rare hereditary disease that only affects males when a mutation in the Factor IX (FIX) gene causes insufficient blood clotting. The novel therapy AMT-060, which comprises a codon-optimized wild type FIX gene cassette, the LP1 liver promoter, and an AAV5 viral vector, was possible to manufacture because of the company’s proprietary insect cell-based technology platform.
The oral presentation included a comprehensive overview of the results from five patients who received a one-time dose of AMT-060, at the initial low dose of 5×1012 gc/kg.
After the initial low dose of AMT-060, total use of FIX concentrate declined significantly and four patients became free of any prophylactic infusions by the cut-off date. All patients enrolled in the low-dose group saw the disease phenotype improve and achieved continued FIX activity increases with an average of 5.4% six months after treatment.
Before the study, all five patients showed signs of moderate-to-severe hemophilia, including FIX activity levels at 1.5% or inferior which required chronic, prophylactic infusions of FIX concentrate to control bleeding.
“After six months of follow-up, I can say as a clinician who regularly treats hemophilia patients that the impact on the quality of life for these patients treated with AMT-060 is very positive,” said Frank Leebeek, study investigator and professor of Hematology in Erasmus University in Rotterdam, Netherlands, in a press release. “The increases in FIX activity and the overall stability of the activity observed over a 6-month period are cause for optimism, as they are associated with meaningful clinical benefits as well as reduced need for ongoing infusions of recombinant FIX therapy.”
Since the May 31 announcement that all five patients in the second dose group had been treated with a one-time dosing of AMT-060 at 2×1013 gc/kg, AMT-060 continued to demonstrate a very low screening failure rate, with all patients screened in the study testing negative for pre-existing neutralizing antibodies against AAV5.
AMT-060 was again shown to be well tolerated, according to six months of data from the low-dose cohort – also consistent with the highest achieved FIX expression levels reported in a prior study by researchers at St. Jude Children’s Research Hospital.
The results were published in the 2011 and 2014 editions of the New England Journal of Medicine and proved the therapeutic relevance and sustained clinical benefits of AMT-060 for up to four years – with mean FIX activity of 5.1% (ranging from 2.9% to 7.2%).
Soland said researchers “continue to be very encouraged” by the data.
“We have so far in the trial achieved our goal for the low-dose cohort, which is to demonstrate safety and therapeutically relevant, durable increases in FIX activity similar to that which was observed in the landmark St. Jude study. The objective for our second cohort is to show meaningful dose-related increases in FIX activity. Based on the results of our non-human primate dose-ranging studies, we are hopeful to accomplish this goal,” Soland said.