Date: 28-Nov-2019

Akcea, Ionis begin NEURO-TTRansform phase 3 trial for AKCEA-TTR-LRx in patients with polyneuropathy driven by hereditary TTR amyloidosis

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 hereditary TTR amyloidosis, or hATTR amyloidosis. “The initiation of the TTRransform phase 3 programme represents an expansion of our dedication and commitment to the ATTR community. The NEURO-TTRansform study is the first of two phase 3 studies that we expect to initiate with AKCEA-TTR-LRx. Our phase 1 data are encouraging and we are excited about the possibility of delivering a significant advancement for people living with hATTR amyloidosis,” said Damien McDevitt, Ph.D., interim chief executive officer at Akcea. 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 percent. “The phase 1 data of AKCEA-TTR-LRx are consistent with the clinical profile seen across our other LICA programs, highlighting the potential of LICA-engineered therapies to address both rare and more common diseases,” said Brett P. Monia, Ph.D., chief operating officer of Ionis. “We remain dedicated to advancing this important clinical development program as rapidly as possible and are hopeful about the prospect of bringing a new safe and effective treatment to people living with the devastating symptoms of hATTR amyloidosis in the years ahead.” 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: Percent 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 percent change from baseline in serum TTR concentration and change from baseline in mNIS+7. AKCEA-TTR-LRx is an antisense drug that uses Ionis’ advanced LIgand Conjugated Antisense, or LICA, technology. It was discovered by Ionis and is being co-developed by Ionis and Akcea. AKCEA-TTR-LRx inhibits the production of the transthyretin (TTR) protein at its source. AKCEA-TTR-LRx is in development to treat a broad population of patients with both hereditary and wild-type forms of transthyretin amyloidosis, or ATTR amyloidosis. hATTR amyloidosis is a severe, progressive, and life-threatening disease caused by the abnormal formation of the TTR protein and aggregation of TTR amyloid deposits in various tissues and organs throughout the body, including in peripheral nerves, the heart and intestinal tract. The progressive accumulation of TTR amyloid deposits in these organs often leads to intractable peripheral sensorimotor neuropathy, autonomic neuropathy, and/or cardiomyopathy, as well as other disease manifestations. hATTR amyloidosis causes significant morbidity and progressive decline in quality of life, severely impacting activities of daily living. The disease often progresses rapidly and can lead to premature death. The median survival is 4.7 years following diagnosis. As the leader in RNA-targeted drug discovery and development, Ionis has created an efficient, broadly applicable, drug discovery platform called antisense technology that can treat diseases where no other therapeutic approaches have proven effective. Akcea Therapeutics, Inc., a majority-owned affiliate of?Ionis Pharmaceuticals, Inc., is a biopharmaceutical company focused on developing and commercializing drugs to treat patients with serious and rare diseases.