A new study has evaluated inotersen’s ability to slow neuropathic progression, as assessed by the Neuropathy Impairment Score (NIS), in patients with hereditary transthyretin amyloidosis (hATTR).

The study, published in BMC Neurology, also estimated responder definition thresholds for the NIS and NIS lower limb subscale (NIS-LL) to reflect the clinically meaningful benefit of inotersen therapy for each patient.

The research team analyzed data from the phase 3, multinational NEURO-TTR trial on adult patients with hATTR randomized to receive treatment with 300 mg of inotersen sodium administered subcutaneously once per week for 65 weeks or a placebo. Outcome measures included NIS and NIS-LL scores at baseline and at the week 65 visit.

Additional measures included the Polyneuropathy Disability Score (PND) and the lower limb function test, both of which are clinician assessments of ambulatory disability and muscle weakness.

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“In the phase 3 NEURO-TTR trial, patients with [hATTR polyneuropathy] receiving inotersen exhibited slower progression of neuropathic symptoms, relative to patients receiving placebo, as measured by statistically significant treatment differences in change on the muscle weakness, sensation loss, and reflex subscales of the clinician-reported NIS and the NIS-LL,” the authors wrote.

“However, while treatment differences were observed for the total sample, the benefit of inotersen on changes in NIS and NIS-LL scores within subgroups of patients with [hATTR polyneuropathy] defined by key clinical characteristics has not yet been evaluated.”

The results confirmed that most patients experienced clinical benefits from inotersen therapy in terms of slower progression of neuropathic symptoms, including muscle weakness scores and NIS sensation scores, compared to patients given the placebo. The authors were able to estimate responder definition thresholds for meaningful changes in NIS and, particularly, for the NIS muscle weakness subscale.

These results further support the efficacy of inotersen in this patient group, and the establishment of responder definition thresholds enables clinicians to better track the progression of impairment and the effectiveness of treatment at the individual patient level.


Yarlas A, Lovley A, Brown D, Vera-Llonch M, Khella S, Karam C. The impact of inotersen on neuropathy impairment score in patients with hereditary transthyretin amyloidosis with polyneuropathy. BMC Neurol. 2023;23(1):108. doi:10.1186/s12883-023-03116-7