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,” said Morie Gertz, MD, M.A.C.P., Division of Hematology, Roland Seidler Jr. Professor Department of Medicine, College of Medicine, Mayo Distinguished Clinician. “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.
“Data showing symptomatic patients experience a quality of life benefit is truly exciting and provides hope for the amyloidosis community. 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,” said Isabelle Lousada, president and chief executive officer of the Amyloidosis Research Consortium (ARC). “The ARC is committed to building collaborative relationships to advance the best research and speed new therapies to market for this disease that has truly devastated generations of affected families. With no FDA-approved drugs, treatment options are extremely limited and desperately needed.”
“We are grateful to the patients who participated in the NEURO-TTR study, along with their families, the investigators and the broader TTR amyloidosis community, for their dedication, commitment and support. We share the collective sense of urgency to bring a new treatment to patients and their families facing this devastating disease,” said Brett P. Monia, senior vice president of drug discovery and franchise leader for oncology and rare diseases at Ionis Pharmaceuticals. “We are excited about the positive topline results from the Phase 3 NEURO-TTR study. We observed a benefit in disease progression in patients treated with inotersen, regardless of disease stage (Stage 1 and Stage 2) or TTR mutation (V30M and non-V30M). We believe these preliminary results suggest a favorable benefit-risk profile for inotersen in patients with FAP.”
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.
Filed Under: Drug Discovery