Rare Daily Staff

Ionis Pharmaceuticals said it submitted a new drug application to the U.S. Food and Drug Administration for inotersen, an experimental drug for the treatment of patients with hereditary TTR amyloidosis, rare, progressive, and fatal condition.

The filing follow’s a late-stage study of inotersen that showed patients treated with the drug experienced significant benefit in their quality of life and in measures of neurological disease compared to placebo-treated patients. It found 50 percent of inotersen-treated patients improved in their quality of life from baseline.

“Today, patients with hATTR have no approved therapeutic options in the U.S. and are often misdiagnosed over the course of many years because symptoms of the disease overlap with other, more common conditions. This can lead to ineffective, costly and often unnecessary invasive treatment,” said Morie Gertz, Chair of the Department of Internal Medicine Mayo Clinic in Rochester, Minnesota and study author. “As we move closer to having a potential therapeutic option to treat this patient population, I am hopeful that physicians will begin to keep hATTR top-of-mind, so that they can connect seemingly disparate symptoms, speed diagnosis and give patients the opportunity to most fully benefit from therapy.”

Inotersen is an antisense drug designed to reduce the production of transthyretin, or TTR, to treat patients with TTR amyloidosis. In patients with ATTR, TTR builds up as fibrils in tissues, such as the peripheral nerves, heart, gastrointestinal system, eyes, kidneys, central nervous system, thyroid, and bone marrow. The presence of TTR fibrils interferes with the normal functions of these tissues. As the TTR protein fibrils enlarge, more tissue damage occurs, and the disease worsens, resulting in poor quality of life and eventually death.

Two key safety issues were identified during the study: thrombocytopenia and safety signals related to renal function. 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.

The overall mortality rate in the study was 2.9 percent and was lower than mortality rates reported in other studies in hATTR patients. There was a total of five deaths in the study, five (4.7 percent) 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. There was one fatal intracranial hemorrhage in conjunction with serious thrombocytopenia. No serious thrombocytopenia was observed following implementation of more frequent monitoring.

Inotersen is under regulatory review for marketing authorization in the United States and European Union. The U.S. Food and Drug Administration has granted Orphan Drug Designation and Fast Track Status to inotersen for the treatment of patients with polyneuropathy due to hATTR. The European Medicines Agency has granted Accelerated Assessment and Orphan Drug Designation to inotersen for the treatment of patients with ATTR.

November 7, 2017

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