Alnylam Pharmaceuticals ($ALNY) has announced positive clinical results from its U.K. Phase I trial of an infusion of ALN-TTR02, an RNAi therapeutic in development for the treatment of TTR-mediated amyloidosis (ATTR). The therapeutic was delivered using Tekmira Pharmaceuticals' ($TKMR) LNP technology, lipid nanoparticles that encapsulate the nucleic acid and deliver it to the disease site.
RNAi (RNA interference) uses small interfering RNAs (siRNAs), short strands of genetic material that can "silence" defective genes. But not only are these targeted by the immune system as "foreign," and so run the risk of being destroyed, but they also cannot cross cell membranes to get to their target. Tekmira's LNP technology protects the siRNAs in the bloodstream and helps the molecules to be taken up by the target cells.
ATTR is a hereditary disease caused by mutations in the TTR gene, which causes nerve and heart damage, potentially leading to death 5 to 15 years after symptom onset. ALN-TTR02 quickly suppressed the TTR protein up 94% in the healthy volunteers after just a single dose, and this was sustained at nearly 80% after one month. According to Akshay Vaishnaw, executive vice president and CMO at Alnylam, reducing levels of TTR just 50% can stabilize or improve the disease. This could mean that the therapeutic only needs to be given once a month or even once every two months
"I am impressed with the almost complete knockdown of TTR after just a single dose of drug, which is important since TTR protein reduction in patients with ATTR has the potential to delay or even reverse disease progression with associated clinical benefits," said Teresa Coelho, a director at Unidade Clinica de Paramiloidose.
This study was not designed to indicate clinical efficacy, so however positive the outcomes are, it is still early for this therapeutic. In order to begin to look at efficacy and dosing schedules, Alnylam has started a Phase II study that will include around 20 ATTR patients receiving treatment every four weeks, and plans to begin a pivotal Phase III trial for this orphan indication next year.
The beginning of the Phase II trial triggered a payment to Tekmira. Tekmira and Alnylam have battled over rights to siRNA and lipid nanoparticle drug delivery technology.
- read the press release from Tekmira
- see the press release from Alnylam
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