Alnylam Pharmaceuticals has announced the final results from its completed Phase 1 clinical trial with ALN-TTR01, an RNAi therapeutic targeting transthyretin (TTR) for the treatment of TTR-mediated amyloidosis (ATTR).

ALN-TTR01 is a systemically delivered RNAi therapeutic that employs first-generation lipid nanoparticle (LNP) technology.

In the randomised, placebo-controlled, single-dose escalation Phase 1 study, patients with ATTR were enrolled in seven sequential cohorts of increasing doses ranging from 0.01mg/kg to 1mg/kg.

The study data demonstrated that administration of ALN-TTR01 resulted in considerable reductions in serum TTR protein levels, including both wild-type and mutant TTR protein, in ATTR patients.

"Administration of ALN-TTR01 resulted in considerable reductions in serum TTR protein levels."

ALN-TTR01 also showed a dose-dependent reduction in serum TTR levels, with a mean reduction of 38% at approximately day 7 to 10 in the 1mg/kg group.

Jared Gollob, Alnylam Pharmaceuticals’ clinical research senior director, said the Phase 1 data from the ALN-TTR01 clinical study demonstrates rapid, dose-dependent and durable lowering of TTR protein levels after a single dose in ATTR patients.

"Further, the full-time course for TTR knockdown after a single dose confirms our expectations for a once a month, or possibly even a once every two month, dosing regimen in our further studies," Gollob added.

"We believe these data with ALN-TTR01 provide key human proof of concept, as we advance ALN-TTR02 as our ‘go-to-market’ RNAi therapeutic for the treatment of ATTR, a debilitating orphan genetic disease."

Alnylam is also developing ALN-TTR02, which utilises second-generation LNP delivery technology and is currently being tested in a Phase 1 clinical study for the treatment of ATTR.

The Phase 1 data from ALN-TTR02 trial is expected to be announced in the third quarter of 2012.

The company is also planning to commence a Phase 2 multi-dose study of ALN-TTR02 in the second half of 2012 and, supposing positive results, anticipates beginning a pivotal trial for ALN-TTR02 in 2013.