Alnylam Pharmaceuticals has completed enrolment in its Phase II trial with ALN-TTR02, an RNAi therapeutic targeting the transthyretin (TTR) gene for the treatment of TTR-mediated amyloidosis (ATTR).
ALN-TTR02 is reported to have achieved about 93% knockdown of TTR, the disease-causing protein in ATTR, in the recent interim results from the Phase II study.
In the study, ALN-TTR02 activity was found to be rapid, dose dependent, and durable, with similar levels of TTR knockdown observed toward both wild-type and mutant protein.
ALN-TTR02 was also found to be generally safe and well tolerated in the study.
The Phase II study, an open-label, multi-centre, multi-dose, dose-escalation trial to evaluate the safety and tolerability of two doses of ALN-TTR02 enrolled 29 ATTR polyneuropathy patients with ALN-TTR02 administered at doses of 0.01 to 0.30 mg/kg, using either a once-every-four-week or once-every-three-week dosing regimen.
Final data from this Phase II study will be presented at the IXth International Symposium on Familial Amyloidotic Polyneuropathy (ISFAP) to be held in Rio de Janeiro, Brazil, 10-13 November.
Currently, the company is also enrolling patients for its open-label extension (OLE) study with ALN-TTR02.
The OLE study will assess the long-term safety and tolerability of ALN-TTR02 and will also measure effects of treatment toward a number of clinical endpoints, including a Neuropathy Impairment Score, or NIS.
Eligible patients treated in the Phase II study can enrol in this study, where they will receive ALN-TTR02 at a dose of 0.3mg/kg every three weeks for up to two years.
Alnylam expects to report clinical data from the OLE study about once per year, with initial data due to be revealed in 2014.
Alnylam Pharmaceuticals executive vice president and chief medical officer Akshay Vaishnaw said the company's ATTR programme is the lead effort in its 'Alnylam 5x15' product development and commercialisation strategy, which is focused on advancing RNAi therapeutics toward genetically defined targets for the treatment of diseases with high unmet medical need.
"We are very encouraged with the clinical activity, safety, and tolerability seen to date with ALN-TTR02 in our Phase II multi-dose study performed in ATTR patients, and look forward to sharing further data at the upcoming ISFAP meeting in November," Vaishnaw said.
In addition, Alnylam also said it plans to begin a Phase III pivotal trial for ALN-TTR02 in familial amyloidotic polyneuropathy patients by the end of 2013.
The company said the primary endpoint will be the difference in the change from baseline in the mNIS+7 score between patients receiving ALN-TTR02 as compared with those receiving placebo.
Alnylam has obtained scientific advice for the ALN-TTR02 Phase III study from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) and has completed its End-of-Phase II meeting with the US Food and Drug Administration (FDA).
Alnylam and Genzyme, a Sanofi company, have entered into an exclusive alliance to develop and commercialise RNAi therapeutics, including ALN-TTR02 and ALN-TTRsc, for the treatment of ATTR in Japan and the broader Asian-Pacific region in 2012.
Alnylam will likely develop and commercialise the ALN-TTR program in North and South America, Europe, and rest of the world.
Image: RNAi Therapeutic Process. Photo: courtesy of Alnylam Pharmaceuticals.