FDA Approves Second Drug Treatment for Polyneuropathy


The FDA has approved Akcea Therapeutics' inotersen (Tegsedi), an antisense oligonucleotide that inhibits the production of the transthyretin protein (amyloid), for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults.

The FDA has approved inotersen (Tegsedi, Akcea Therapeutics), an antisense oligonucleotide (ASO) that inhibits the production of the transthyretin (TTR) protein (amyloid), for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR) in adults.1,2 This is the second FDA approved drug for hATTR, following patisiran (Onpattro), which was approved August 10.1

FDA Approves First Targeted Treatment of Polyneuropathy in Rare Disease

hATTR is a rare, debilitating, and often fatal genetic disease characterized by the buildup of abnormal amyloid protein in peripheral nerves, the heart, and other organs, interfering with their normal functioning. The clinical signs and symptoms of amyloid deposition in the peripheral nervous system can include effects on sensation, autonomic function, and muscle strength.1 n hATTR amyloidosis, transthyretin (TTR) protein misfolds and accumulates as amyloid deposits throughout the body. Inotersen targets the disease at its source by reducing the production of TTR protein.2

According to Isabelle Lousada, founder and chief executive officer of the Amyloidosis Research Consortium, hATTR is significantly underdiagnosed, and the true incidence of hATTR amyloidosis with polyneuropathy is unknown. “This (drug) approval represents a significant advancement for the patients, families, caregivers and healthcare professionals in the United States who need more options for the medical management of this disease," said Lousada, in a prepared statement.2 "I am now more optimistic than ever that we can increase awareness of this rare disease, support faster diagnosis and provide better treatment.”

The FDA’s approval of Tegsedi was based on results from the Phase 3 NEURO-TTR study in patients with hATTR amyloidosis with symptoms of polyneuropathy. Results from that study demonstrated that patients treated with Tegsedi experienced significant benefit compared to patients treated with placebo across both co-primary endpoints: the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QoL-DN) and modified Neuropathy Impairment Score +7 (mNIS+7), a measure of neuropathic disease progression. In the NEURO-TTR study, treatment with inotersen produced up to a 79% mean decrease from baseline in serum TTR protein in patients regardless of TTR mutation, sex, age, or race.2

“Tegsedi has demonstrated a nearly 80% reduction in TTR, which is now a validated approach to treating this disease. The rapid and sustained improvements compared to placebo and reversal in measures of disease seen in a substantial proportion of patients coupled with the independence offered through self injection provide a sense of hope not only to patients, but to their caregivers and families as well," said Morie Gertz, MD, hematologist and Chair Emeritus of Internal Medicine at Mayo Clinic, in a prepared statement.2

Inotersen is contraindicated in patients with a history of acute glomerulonephritis caused by the drug, patients with a history of a hypersensitivity reaction to inotersen, and patients with a platelet count less than 100 x 109 /L. Tegsedi’s label contains a Boxed Warning about low blood platelet count, which may be life threatening, and glomerulonephritis which may require immunosuppressive treatment and may result in dialysis-dependent renal failure. Laboratory monitoring for both conditions is required before, during, and after treatment discontinuation. Because of the risks of serious bleeding due to severe thrombocytopenia and glomerulonephritis, inotersen is available only through a restricted distribution program under a Risk Evaluation and Mitigation Strategy (REMS) called the Tegsedi REMS Program.1

Tegsedi’s label also contains warnings about stroke and cervical artery dissection, inflammatory and immune effects, including serious neurologic adverse reactions; liver effects, hypersensitivity reactions, a potential interaction that can lead to uninterpretable platelet counts, and reduced serum vitamin A levels, which pertains to ocular toxicity. The most common adverse reactions observed in the clinical efficacy trial with Tegsedi were injection site reactions, nausea, headache, fatigue, thrombocytopenia, and fever.1

In an effort to assist hATTR amyloidosis patients in gaining access to Tegsedi, Akcea has created Akcea ConnectTM, a patient support program made up of dedicated, regionally-based nurse case managers with a wide range of medical knowledge and experience. This program offers free, private and personalized support to patients, their caregivers and families in the United States.2

“hATTR amyloidosis is a devastating disease that takes so much from patients. Akcea is ready to help patients take something back,” said Sarah Boyce, president of Akcea Therapeutics, in a prepared statement.2 “We understand that managing a rare disease goes beyond providing a new medicine and our highly skilled team is fully prepared to provide an effective, safe and comprehensive treatment experience.


  • FDA Division of Drug Information. FDA approves new drug for treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis - Drug Information Update. [email] October 5, 2018
  • Akcea and Ionis Receive FDA Approval of TEGSEDI™ (inotersen) for the Treatment of the Polyneuropathy of Hereditary Transthyretin-Mediated Amyloidosis in Adults [news release]. Boston, MA and Carlsbad, CA; October 5, 2018: Akcea Therapeutics and Ionis Pharmacueticals. http://ir.akceatx.com/news-releases/news-release-details/akcea-and-ionis-receive-fda-approval-tegseditm-inotersen. Accessed October 2018.

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