Ionis Pharmaceuticals announced the Phase 3 NEURO-TTR study of inotersen (IONIS-TTRRx) in patients with familial amyloid polyneuropathy (FAP) met both primary endpoints. Over the 15-month period of the study, inotersen-treated patients achieved statistically significant benefit compared to placebo in the modified Neuropathy Impairment Score +7 (mNIS+7) and the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QoL-DN) (p<0.0001 and p=0.0006, respectively). Statistically significant differences were also observed for both endpoints at eight months.

"Familial amyloid polyneuropathy is a devastating genetic disease that is painful and rapidly progressive leading to early death. The positive results from the NEURO-TTR study today are very encouraging for this underserved patient population," Morie Gertz, MD, M.A.C.P., Division of Hematology, Roland Seidler Jr. Professor Department of Medicine, College of Medicine, Mayo Distinguished Clinician said. "I have been treating patients with this disabling disease for many years, and I am excited about the promise that inotersen holds to restore their lives. I believe inotersen has the potential to transform the current standard of care for patients with TTR amyloidosis."

Treatment-emergent adverse events considered related to treatment were seen more commonly with inotersen than placebo. Two key safety findings were observed during the study that required changes to the monitoring schedule. Three serious adverse events of thrombocytopenia were observed in inotersen-treated patients; two patients recovered and one patient died due to intracranial hemorrhage. One additional inotersen-treated patient discontinued treatment due to non-serious thrombocytopenia. Four inotersen-treated patients discontinued treatment due to a renal observation; two patients met a predefined renal stopping rule and two experienced serious renal adverse events, one of whom experienced chronic renal insufficiency. One placebo-treated patient also met a predefined renal stopping rule. Enhanced monitoring was implemented during the study to support early detection and management of the thrombocytopenia and renal issues. All five serious adverse events occurred before enhanced monitoring was fully implemented. A detailed review of safety data from the study is ongoing.

Long-term safety and efficacy data with inotersen are currently being collected in an open-label extension of the Phase 3 NEURO-TTR study. More than 80% of patients completed the NEURO-TTR study, of these more than 95% participated in the open-label extension study.

Review of the full data package from the NEURO-TTR study by Ionis and GSK is ongoing and detailed results from the study will be presented at an upcoming medical meeting and submitted for publication in a peer-reviewed medical journal.

The preparation of regulatory marketing applications for inotersen is underway. GSK has the option to license inotersen following review of additional data and prior to the submission of regulatory applications.