The company says it plans to file an investigational new drug application (IND) with the U.S. Food and Drug Administration (FDA) in the second half of 2018. The first human clinical trial with AMT-130 should begin soon after the FDA’s anticipated acceptance.
“We ended 2017 with significant momentum across all of our programs and the cash to fund operations into 2020. Now that we have established robust, commercial-scale manufacturing in our Lexington [Massachusetts] facility, we are highly focused on the near-term initiation of our pivotal study of AMT-061 in hemophilia B and Phase I/II trial of AMT-130 in Huntington’s disease,” Matthew Kapusta, CEO of uniQure, said in a press release.
AMT-130 is an experimental gene therapy that works by inhibiting the production of the mutated or altered form of the huntingtin protein. It does this by carrying a small molecule, called microRNA, that binds to the messenger molecule carrying instructions for the production of the huntingtin protein and sends it to degradation. As a result, AMT-130 lowers the levels of the defective huntingtin protein.
The therapy is carried by a special class of virus – called adeno-associated virus (AAV) – that is unable to cause an infection to its host, working just as a vehicle to deliver AMT-130 to nerve cells. The internalization of AMT-130 is mediated by the internalization of the virus. Once inside the cell, the miRNA is capable of binding to the messenger RNA molecule for huntingtin.
If the IND application is accepted, AMT-130 would become the first AAV-based gene therapy tested in humans, according to uniQure.
uniQure has previously shown that AMT-130 improves motor coordination and survival in mouse models of Huntington’s disease (HD). These results were followed by a report showing that the therapy was able to penetrate the brain and spinal cord following direct injection in a primate.
The therapy received FDA’s orphan drug designation in October 2017.
“We also are intensifying efforts to further expand our gene therapy product pipeline. In addition to AMT-126, our BMS [Bristol-Myers Squibb]-partnered gene therapy candidate for congestive heart failure, we have a number of promising early-stage projects focused on liver-directed and CNS [central nervous system] disorders. We expect multiple new INDs to be filed over the next two years, further leveraging our industry-leading manufacturing and technology platform,” Kapusta stated.