Alnylam Pharmaceuticals this week announced positive data from a phase II trial of its TTR-mediated amyloidosis drug patisiran, formerly ALN-TTR02, showing that the drug triggered "robust and statistically significant" inhibition of its target protein.
The company also announced that it has begun a phase III trial of the drug in patients with a manifestation of the disease called familial amyloidotic polyneuropathy, or FAP.
ATTR is caused by mutations in the TTR gene, which triggers accumulation of abnormal amyloid proteins in the body. Patisiran comprises siRNAs designed to inhibit both the wild-type and mutant forms of the protein.
According to Alnylam, the new phase II data from 28 ATTR polyneuropathy patients showed that multiple doses of patisiran resulted in rapid, dose-dependent, and durable knockdown of serum TTR levels.
The drug was administered either once every four weeks or once every three weeks at doses ranging from 0.1 mg/kg to 0.3 mg/kg. At the highest dose, TTR levels were cut by up to 96 percent.
In phase II, multiple doses of patisiran were found to be generally safe and well tolerated in this study, the company said. "The majority of the adverse events were mild or moderate. There were no abnormalities seen in liver function tests, renal function, or hematologic parameters."
The data were presented at the IXth International Symposium on Familial Amyloidotic Polyneuropathy.
As a result, Alnylam is pursuing a once-every-three-weeks dosing schedule at 0.3 mg/kg in the phase III study. That trial, dubbed APOLLO, is a randomized, double-blind, placebo-controlled, global study designed to evaluate the efficacy and safety of patisiran in ATTR patients with FAP.
The primary endpoint is a difference in change from baseline as measured by a modified neuropathy impairment scoring system after 18 months in patients receiving patisiran and those receiving placebo.