Akcea Therapeutics to Present Data on Inotersen for the Treatment of hATTR Amyloidosis at the 2018 American Academy of Neurology Annual Meeting
Two oral presentations further demonstrate inotersen’s impact on efficacy and safety and on patient quality of life

CAMBRIDGE, Mass.April 21, 2018 (GLOBE NEWSWIRE) -- Akcea Therapeutics, Inc. (Nasdaq:AKCA), an affiliate of Ionis Pharmaceuticals, Inc., today announced that data from inotersen’s clinical development program for the treatment of hereditary ATTR (hATTR) amyloidosis will be presented at the American Academy of Neurology (AAN) Annual Meeting in Los Angeles, Calif.April 21-27, 2018.

“We are pleased to have the opportunity to present data from the NEURO-TTR study in two oral presentations at this year’s American Academy of Neurology Annual Meeting. These data, combined with the sustained efficacy in the open label extension study, continue to demonstrate that inotersen has the potential to significantly benefit people living with hATTR amyloidosis,” said Sarah Boyce, president of Akcea Therapeutics.

In addition to the oral presentations, two posters regarding one-year follow-up results of an open-label extension of the Phase 3 NEURO-TTR study and the disease burden of hATTR amyloidosis will also be presented.

AAN Oral Presentations

  • Sunday, April 22, 2018 at 2:00pm PT – P. James B. Dyck, M.D., Mayo Clinic
    • S5.006: Inotersen Improves Norfolk Quality of Life-Diabetic Neuropathy Measures in Patients With Hereditary Transthyretin Amyloidosis with Polyneuropathy in the Phase 3 Study NEURO-TTR
  • Monday, April 23, 2018 at 4:30pm PT – John Berk, M.D., Boston University
    • N2.001: Safety and Efficacy of Inotersen in Patients With Hereditary Transthyretin Amyloidosis With Polyneuropathy (NEURO-TTR)

AAN Poster Presentations

  • Sunday, April 22, 2018 from 11:30am – 5:30pm PT
    • P1.324: Open Label Extension of the Phase 3 Study NEURO-TTR to Assess the Long-term Efficacy and Safety of Inotersen in Patients With Hereditary Transthyretin Amyloidosis
    • P1.331: Burden of Hereditary Transthyretin Amyloidosis With Polyneuropathy in Patients Enrolled in the Phase 3 Study NEURO-TTR

For the 2018 program and a full list of presentations, please visit the AAN website at


Inotersen is an antisense drug designed to reduce the production of transthyretin, or TTR protein, to treat ATTR amyloidosis, a systemic, progressive and fatal disease. Inotersen is currently under Priority Review for marketing authorization in the U.S. and Accelerated Assessment in the EU. The U.S. Food and Drug Administration has granted inotersen Orphan Drug Designation and Fast Track Status, and the European Medicines Agency has granted inotersen Orphan Drug Designation.

The NEURO-TTR study was a Phase 3 randomized (2:1), double-blind, placebo-controlled, international study in 172 patients with polyneuropathy due to hATTR amyloidosis. The 15-month study measured the effects of inotersen on neurological dysfunction and on quality-of-life by measuring the change from baseline in the modified Neuropathy Impairment Score +7 (mNIS+7) and in the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QOL-DN) total score. The NEURO-TTR OLE is an ongoing study for patients who completed the NEURO-TTR study and is intended to evaluate the long-term efficacy and safety profile of inotersen.

Results from the Phase 3 NEURO-TTR study demonstrated that most inotersen-treated patients experienced substantial reductions in TTR.  Nearly 90% of patients achieved >50% TTR reduction and nearly 50% of patients achieved over 75% TTR reduction at 15 months. Median TTR reduction was 75-79% between weeks 13-65. These TTR reductions were associated with positive outcomes compared to placebo in both primary endpoints of the study: the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QoL-DN) and the modified Neuropathy Impairment Score +7 (mNIS+7) at both eight and 15 months of treatment. In addition, consistent positive outcomes were observed in both the Norfolk QoL-DN and mNIS+7, independent of disease stage, types of mutation or presence of cardiomyopathy at the beginning of the study. Inotersen-treated patients showed  positive outcomes in the quality of life primary endpoint with 50% of patients experiencing improved scores compared to baseline and a mean difference in magnitude of 11.68 points, compared to placebo-treated patients, at 15 months of treatment (mean change from baseline of 0.99 vs. 12.67, p<0.001). In addition, clinically meaningful positive outcomes  compared to placebo were observed in the SF-36 physical component score, a measure of general health quality of life. Inotersen-treated patients also was seen in the co-primary endpoint of disease control, mNIS+7, with 37% of patients experiencing improved scores compared to baseline and a mean difference in magnitude of 19.73 -points, compared to placebo-treated patients, at 15 months of treatment, (p < 0.001). Whether or not a patient improved in either Norfolk QOL-DN or mNIS+7 could not be predicted by TTR reduction alone. Most patients achieved benefit regardless of whether they were in the 50-75% reduction range or in the 75-95% reduction range.

Positive outcomes were observed in inotersen-treated patients with cardiac disease at baseline (interventricular septum thickness, IVS ≥ 1.5 cm) in both primary endpoints (Norfolk QoL-DN, p=0.036 and mNIS+7, p<0.001) and in the SF-36 Health Survey endpoint (p=0.025) at 15 months, compared to placebo. Encouraging outcomes also were observed in multiple cardiac measures, including mean decreases in left ventricle mass (p=0.0288), IVS (p=0.0150) and posterior wall thickness (p=0.0425), which increased, on average, in placebo-treated patients.

Thrombocytopenia and safety signals related to renal function were identified during the study. Enhanced monitoring was implemented during the study to support early detection and management of these issues. Serious platelet and renal events were infrequent and easily managed with routine monitoring, which has proven effective since implementation. Other serious adverse events were observed in 24.1% of inotersen-treated patients and 21.7% of placebo-treated patients. No cumulative toxicities have been identified with long-term exposure.

Adverse events occurring in >=10% of patients and twice as frequently in inotersen-treated patients compared with placebo-treated patients, included thrombocytopenia/platelet count decreases, nausea, pyrexia, chills, vomiting, and anemia. Injection site reactions accounted for less than 1% of all injections and were mild or moderate in severity. There were no discontinuations due to injection site reactions. The overall mortality rate in the NEURO-TTR study was 2.9% and was lower than overall mortality rates reported in other studies in hATTR patients. There was a total of five deaths in the study, five (4.7%) in the inotersen arm and zero in the placebo arm. Four deaths in the inotersen arm were associated with disease progression and considered unrelated to treatment. As previously reported, there was one fatal intracranial hemorrhage in conjunction with serious thrombocytopenia. No serious thrombocytopenia was observed following implementation of more frequent monitoring.

The inotersen expanded access program (EAP) has been initiated for eligible patients in the U.S.


hATTR amyloidosis is a progressive, systemic and fatal genetic disease caused by the inappropriate formation and aggregation of TTR amyloid deposits in various tissues and organs throughout the body, including in peripheral nerves, heart, intestinal tract, eyes, kidneys, central nervous system, thyroid and bone marrow. The progressive accumulation of TTR amyloid deposits in these tissues and organs leads to sensory, motor and autonomic dysfunction often having debilitating effects on multiple aspects of a patient's life. Patients with hATTR amyloidosis often present with a mixed phenotype and experience overlapping symptoms of polyneuropathy and cardiomyopathy.

Ultimately, hATTR amyloidosis results in death within three to fifteen years of symptom onset. Therapeutic options for the treatment of patients with hATTR amyloidosis are limited and there are currently no disease-modifying drugs approved for the disease. There are an estimated 50,000 patients with hATTR amyloidosis worldwide.  Additional information on hATTR amyloidosis, including a full list of organizations supporting the hATTR amyloidosis community worldwide, is available at

Akcea Therapeutics, an affiliate of Ionis Pharmaceuticals, Inc. (NASDAQ:IONS), is a biopharmaceutical company focused on developing and commercializing drugs to treat patients with serious and rare diseases. Akcea is advancing a mature pipeline of six novel drugs, including inotersen, volanesorsen, AKCEA-APO(a)-LRx, AKCEA-ANGPTL3-LRx, AKCEA-APOCIII-LRx, and AKCEA-TTR-LRx, all with the potential to treat multiple diseases. All six drugs were discovered by and are being co-developed with Ionis, a leader in antisense therapeutics, and are based on Ionis’ proprietary antisense technology. Inotersen is under regulatory review in the U.S. and EU for the treatment of hereditary amyloid transthyretin amyloidosis (hATTR) amyloidosis. Volanesorsen is under regulatory review in the U.S., EU and Canada for the treatment of familial chylomicronemia syndrome, or FCS, and is currently in Phase 3 clinical development for the treatment of familial partial lipodystrophy, or FPL. Akcea is building the infrastructure to commercialize its drugs globally. Akcea is a global company headquartered in Cambridge, Massachusetts. Additional information about Akcea is available at

This press release includes forward-looking statements regarding the business of Akcea Therapeutics, Inc. and the therapeutic and commercial potential of inotersen and other products in development. Any statement describing Akcea’s goals, expectations, financial or other projections, intentions or beliefs is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties, particularly those inherent in the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such drugs. Akcea’s forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Akcea’s forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Akcea. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Akcea’s programs are described in additional detail in its annual report on Form 10-K for the year ended December 31, 2017, which is on file with the SEC.

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