Dutch gene therapy firm UniQure and academic collaborators have been awarded a three-year grant worth €2.5 million ($3.2 million) from the European Commission to develop a treatment for Huntington’s disease that combines RNAi and gene replacement.
With the new funding, UniQure now aims to be able to advance the therapy into phase I testing in 2016 as it joins a growing list of companies looking to use RNA drugs to treat the disease.
UniQure’s primary focus has long been on gene replacement therapies, and the company recently received European approval for its lipoprotein lipase deficiency treatment Glybera. However, it has also been eyeing other opportunities to apply its core adeno-associated virus technology and saw RNAi as a promising new direction.
To that end, in late 2012, the company signed a deal to acquire a non-exclusive license to use Benitec Biopharma’s expressed RNAi technology to develop a Huntington’s disease treatment (GSN 12/6/2012). In exchange, Benitec received the right to use UniQure’s AAV serotype 5, or AAV5, technology in its preclinical hepatitis B drug Hepbarna.
At the time, Hans Preusting, senior VP of business development at UniQure, said that the company had already conducted early-stage discovery work exploring expressed RNAi for Huntington’s disease, and that experiments in animal models were slated for 2013. He did not, however, provide specific details about the treatment approach.
This week, UniQure disclosed that the therapy has two therapeutic components, both of which utilize its AAV5 delivery technology.
The first is an artificial microRNA expressing inhibitory RNAs against the huntingtin gene, which is mutated in Huntington’s disease. The second is a gene-expression system for glial cell-derived neurotrophic factor, which has been shown to have neuroprotective properties in animal models of the disease.
Under the grant, which was awarded through the EC’s Eurostars program, UniQure will work with Lausanne University Hospital in Switzerland, University Medical Center Gottingen in Germany, and Maria Curie-Skłodowska University in Poland.
The primary objective of the grant program is to establish the safety and efficacy of the RNAi/gene-expression therapy in rodent models of Huntington’s disease and in marmoset brains.
Assuming positive results, Preusting said in an email this week that a phase I study of the treatment could start within three years. He noted that, given the added support of the Eurostars grant, UniQure expects to be able to conduct that trial without a partner.
In taking on Huntington’s disease, UniQure has become the latest drugmaker to try developing an RNA-based treatment for the condition.
In 2005, Alnylam Pharmaceuticals joined up with medical device firm Medtronic to create an implantable infusion system that would deliver huntingtin-targeted siRNAs into the central nervous system of Huntington’s disease patients (GSN 2/11/2005).
Five years later, the non-profit Huntington's disease organization CHDI Foundation agreed to support their work by taking on half of the cost of advancing the treatment, called ALN-HTT, up to an investigational new drug application filing.
Despite promising preclinical data, Alnylam undertook a corporate restructuring in early 2012, cutting a third of its workforce as it refocused and streamlined its research and development efforts. By May of that year, the company announced it was ending its involvement in Huntington’s disease, although Medtronic continues to advance the RNAi-based therapy.
Meanwhile, in 2011 Danish drug firm Lundbeck started working on its own RNAi treatment for Huntington’s disease in collaboration with the University of Massachusetts Medical School (GSN 2/3/2011).
That early-stage work is primarily being conducted in the lab of UMMS researcher Neil Aronin, with the financial support of Lundbeck.
Perhaps the most ambitious effort in the space belongs to Isis Pharmaceuticals, which last month partnered with Roche to develop antisense-based Huntington’s disease drugs.
Under that arrangement, Isis will develop antisense agents that inhibit huntingtin, as well as oligos that specifically target the mutant form of the protein. Roche, meanwhile, is developing its so-called brain shuttle technology to deliver antisense compounds across the blood-brain barrier, which would allow for the systemic administration of a Huntington’s disease drug.
Roche has the option to license drugs resulting from the arrangement up through the completion of phase I trials, and paid Isis $30 million upfront. Isis stands to receive as much as $362 million in total license fees and milestones under the deal, plus royalties.
Meanwhile, several academic groups are tackling Huntington’s disease using RNAi, including University of Iowa’s Beverly Davidson, who previously demonstrated the therapeutic benefit of partial huntingtin suppression in rodent disease models and, in late 2011, published data showing that such an approach is safe in non-human primates.