OLE study of Onpattro shows benefits for polyneuropathy of hATTR amyloidosis.- Alnylam Pharma

Alnylam Pharmaceuticals presented new results from the Global Open-Label Extension (OLE) study of Onpattro (patisiran), an RNAi therapeutic for the treatment of the polyneuropathy of hereditary ATTR (hATTR) amyloidosis in adults, at the European Academy of Neurology (EAN) Virtual Congress. In addition, interim results were presented from a Phase IIIb trial evaluating treatment with patisiran in patients with hATTR amyloidosis with disease progression after receiving an orthotopic liver transplant (post-OLT). 24-month interim results were presented from the ongoing Global OLE study of patisiran evaluating the drug’s long-term efficacy and safety in eligible patients (N=211) who completed the Phase II OLE (N=25) and APOLLO Phase III (N=186) studies. The data shared include 178 patients who had 24 months or greater of exposure as of an October 7, 2019 cutoff date. Reductions in serum TTR levels were maintained in patisiran-treated patients with continued dosing in the Global OLE study. Patients on treatment for 42 months demonstrated sustained improvement in neuropathy impairment and quality of life relative to APOLLO study baseline, as shown by mean negative changes in modified Neuropathy Impairment Score + 7 (mNIS+7) and Norfolk Quality of Life – Diabetic Neuropathy (QOL-DN) scores. Patients on treatment from the Phase II OLE population also demonstrated an improvement in mNIS+7 score over 48 months. For APOLLO placebo patients subsequently treated with patisiran for 24 months in the OLE study, neuropathy progression was also notably halted and QOL improved. However, these patients had experienced rapid progression while on placebo in the APOLLO study and did not return to their baseline scores, highlighting the importance of patients starting treatment with patisiran early. The long-term safety profile of patisiran was consistent with that observed and previously reported in the APOLLO Phase III study and the Phase II OLE study. In addition, data were presented from an interim analysis of the Phase IIIb open-label study conducted across several European countries to evaluate the safety, efficacy and pharmacokinetics (PK) of patisiran in patients with hATTR amyloidosis with disease progression after receiving an orthotopic liver transplant (OLT). Historically, OLT has been used to slow disease progression in patients with early stages of hATTR amyloidosis; however, some patients experience disease progression after the transplant due to continued amyloid deposition of wild-type TTR on top of existing amyloid deposits in tissues. Twenty-three patients who showed disease progression post-OLT (based on an increase in polyneuropathy disability [PND] score) received patisiran infusion (0.3 mg/kg) every three weeks. After 3 weeks of patisiran treatment, the mean reduction from baseline in serum TTR levels was 81.9 percent. At the time of interim safety analysis (data cutoff as of December 9, 2019), the safety profile of patisiran in this Phase IIIb study was consistent with that observed and previously reported in the APOLLO Phase III study. The safety, efficacy, and PK of patisiran treatment post-OLT will be further investigated in this ongoing study.