Akcea Therapeutics, Inc, a majority-owned affiliate of Ionis Pharmaceuticals, Inc., and Ionis Pharmaceuticals, Inc. announced initiation of the NEURO-TTRansform Phase 3 clinical trial for AKCEA-TTR-LRx in patients with polyneuropathy caused by h856ereditary TTR amyloidosis, or hATTR amyloidosis. AKCEA-TTR-LRx is an antisense drug developed using Ionis' proprietary LIgand Conjugated Antisense (LICA) technology platform and is designed to inhibit production of TTR. It was discovered by Ionis and is being co-developed by Ionis and Akcea.

In a Phase 1 clinical trial, patients treated with AKCEA-TTR-LRx experienced reductions in TTR of up to 94%. NEURO-TTRansform is a global, open-label, randomized study evaluating the efficacy and safety of AKCEA-TTR-LRx in patients with polyneuropathy due to hATTR amyloidosis. The study will enroll 140 adult patients with stage 1 or stage 2 polyneuropathy and will be compared to the historical placebo arm from the TEGSEDI® (inotersen) NEURO-TTR Phase 3 study that was completed in 2017.

Of the total 140 participants, 20 patients will begin on TEGSEDI and move to AKCEA-TTR-LRx after week 35. The primary endpoint analysis will be completed at week 66 and all patients will be followed until week 85 when they will have the option to transition into the open label extension study. The co-primary efficacy endpoints at week 66 are: % change from baseline in serum TTR concentration; Change from baseline in the modified Neuropathy Impairment Score +7 (mNIS+7), a measure of neuropathic disease progression; and Change from baseline in Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QoL-DN).

There will be an interim analysis at week 35 where the co-primary efficacy endpoints are % change from baseline in serum TTR concentration and change from baseline in mNIS+7.