US-based Alnylam Pharmaceuticals has completed patient enrolment in its Phase II clinical trial of an investigational RNAi therapeutic, revusiran (re-VOO-si-ran), the recommended International Nonproprietary Name (INN) for ALN-TTRsc.
Revusiran targets wild-type and all mutant forms of transthyretin (TTR) and uses the company's GalNAc-conjugate delivery platform that allows subcutaneous delivery of RNAi therapeutics with a wide therapeutic index.
TTR-mediated amyloidosis (ATTR) is an inherited, progressively debilitating and often fatal disease caused by mutations in the TTR gene.
A total of 26 patients with TTR cardiac amyloidosis, who received revusiran for a five-week course of treatment, have been enrolled in the pilot Phase II trial.
The pilot Phase II trial is designed to evaluate the safety, tolerability, pharmacodynamic and preliminary clinical activity of revusiran in patients with familial amyloidotic cardiomyopathy (FAC) and senile systemic amyloidosis (SSA).
The trial's primary objective was to evaluate the safety and tolerability of revusiran, while the secondary objectives were to assess the pharmacodynamic effect on serum levels of TTR and characterise the pharmacokinetic profile.
Separately, the company has announced that its open-label extension (OLE) trial with revusiran is now open for enrolment for patients who participated previously in the Phase II clinical trial.
The Phase II OLE trial will evaluate the safety and tolerability of long-term dosing with revusiran for up to two years.
This trial will also measure effects of treatment on clinical endpoints, including mortality, hospitalisation, and six-minute walk distance (6-MWD), in addition to cardiac amyloid burden and function, and cardiac biomarkers.
Alnylam vice-president of Clinical Research Jared Gollob said: "Our Phase I clinical study demonstrated robust knockdown of circulating TTR - the disease-causing gene - of up to 96%, and was generally well tolerated.
"We plan on presenting data from the OLE study at least once annually starting in 2015. Finally, we are pleased to have completed our discussions with US and EU regulatory authorities on the design of our Phase III study, and are on track to initiate the study before year's end."
The company has also reported that it has completed its discussions with regulatory authorities in the US and EU regarding the design of a Phase III trial for revusiran in TTR cardiac amyloidosis patients and it is expected to be started by the end of this year.