Ionis Pharmaceuticals’ antisense drug inotersen (IONIS-TTRRX) met both its primary endpoints in the Phase III NEURO-TTR study in 172 patients with familial amyloid polyneuropathy (FAP). The 15-month placebo-controlled study showed that patients treated with inotersen achieved statistically significant improvements in neurological dysfunction, measured by the modified Neuropathy Impairment Score +7 (mNIS+7), and in quality of life, measured by the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QoL-DN).
The trial was not without its safety concerns, however. There were three serious adverse events of thrombocytopenia among inotersen-treated patients, and one patient died of intracranial hemorrhage. Four inotersen-treated patients also discontinued treatment due to renal issues. Two of these experienced serious renal adverse events, with one developing chronic renal insufficiency.
GSK has an option to license inotersen prior to submission for regulatory approval. Ionis is currently preparing marketing applications for the drug and said both firms will review the full data package from the Phase III NEURO-TTR study. Ionis and GSK signed their preferred partner alliance for IONIS-TTRRX in 2010, under which Ionis is responsible for conducting Phase III studies.
“We are excited about the positive topline results from the Phase III NEURO-TTR study,” said Brett P. Monia, Ph.D., svp for drug discovery and franchise leader for oncology and rare diseases at Ionis. “We observed a benefit in disease progression in patients treated with inotersen, regardless of disease stage (Stage 1 and Stage 2) or transthyretin (TTR) mutation (V30M and non-V30M). We believe these preliminary results suggest a favorable benefit-risk profile for inotersen in patients with FAP.”
An open-label extension study to NEURO-TTR is currently collecting long-term inotersen safety and efficacy data. Eighty per cent of patients completed the NEURO-TTR study, and 95% of these have enrolled into the extension trial.
“Data showing symptomatic patients experience a quality of life benefit is truly exciting and provides hope for the amyloidosis community,” commented Isabelle Lousada, president and CEO of the Amyloidosis Research Consortium (ARC). “We are excited by this very important milestone and welcome the opportunity of inotersen to potentially address the unmet and critical needs of amyloidosis patients and transform lives.”
Last month, Ionis and Suzhou Ribo Life Science signed a collaboration and license agreement to develop two of Ionis’ Generation 2+ antisense drugs for the Chinese market.
Within the last month, Alnylam Pharmaceuticals reported positive data from a Phase II open-label extension study evaluating its RNA interference (RNAi) therapeutic Patisiran (ALN-TTR02) for the treatment of FAP. Patisiran is currently being evaluated in the global Phase III APOLLO study.