Yesterday, Ionis Pharmaceuticals announced the submission of its new drug application (NDA) to the U.S. Food and Drug Administration (FDA) for inotersen, intended to treat patients with hereditary transthyretin (TTR) amyloidosis (hATTR).
Inotersen, an investigational compound, is an antisense drug designed specifically to reduce the production of TTR. It is currently under regulatory review for marketing authorization in the United States and Europe.
hATTR is a severe, potentially fatal rare genetic disease that is the result of a misfolding of TTR proteins, leading to a deposition of amyloid fibrils in different organs, like the peripheral nerves, heart, gastrointestinal system, eyes, kidneys, central nervous system (CNS), thyroid, and bone marrow. In patients with ATTR, the buildup of TTR fibrils interferes with the intended functionality in these tissues and organs, leading to further damage, a poor quality of life, and eventually death.
"The filing of the NDA for inotersen in the U.S. is an important milestone for Ionis. We would like to thank the patients suffering with hATTR, their families and the healthcare professionals who participated in the NEURO-TTR study and were instrumental in reaching this goal,” said Sarah Boyce, chief business officer of Ionis Pharmaceuticals in a press release
. “In the Phase 3 NEURO-TTR study, inotersen-treated patients experienced significant benefit in their quality of life and in measures of neurological disease compared to placebo-treated patients, and 50% of inotersen-treated patients improved in their quality of life from baseline. We believe that the benefit seen with inotersen treatment in the NEURO-TTR study, combined with its superior convenience, could make inotersen the treatment of choice for this patient population.”
The FDA has already granted both Orphan Drug Designation and Fast Track Status to inotersen for the treatment of patients with polyneuropathy due to hATTR.
"As part of our commitment to patients with this devastating, progressive and fatal disease, we have initiated our plan to open an expanded access program for eligible patients, with the first wave of sites to open in the U.S. in the coming months,” Boyce said. “We are also making substantial progress in advancing inotersen to market and are in advanced discussions with potential partners who could work with us to commercialize inotersen outside of North America while we commercialize or co-commercialize inotersen in North America. We believe the right partner can maximize the commercial success of inotersen."
In May, Ionis completed a 15-month long Phase 3 study, NEURO-TTR evaluating the clinical benefit of inotersen in hATTR, and last week, Ionis presented new data
from that study at the ATTR Amyloidosis Meeting in Paris. Results showed that both primary endpoints – Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QoL-DN) and modified Neuropathy Impairment Score +7 (mNIS+7) – were met, and that the drug was strongly favored in comparison to placebo.
During the study, however, 2 different safety issues arose: thrombocytopenia, which was acquired by 3 of the 172 enrolled patients; and serious renal adverse events (AEs), which was experienced by 6 patients. These complications aside, the most common AEs included nausea, chills, vomiting, and anemia.
"I am encouraged by data from the Phase 3 NEURO-TTR study, which demonstrated substantial benefit in both quality of life and disease progression among inotersen-treated patients compared to placebo-treated patients. 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,” said Dr. Morie A. Gertz, Roland Seidler Jr. Professor of the Art of Medicine and Chair of the Department of Internal Medicine Mayo Clinic in Rochester, Minnesota and study author.
There are currently no approved therapeutic options in the U.S. for the treatment of hATTR, and patients are commonly misdiagnosed because of symptoms that overlap with those of other diseases.
For more from Ionis, including submissions of new drug applications, follow Rare Disease Report