NDA for hATTR Treatment Accepted by the Food and Drug Administration

This morning, almost exactly 2 months after Ionis submitted its new drug application (NDA) to the U.S. Food and Drug Administration (FDA), the company has announced that the regulatory agency has accepted its investigational drug inotersen for Priority Review.

Inotersen, intended to treat patients with hereditary transthyretin amyloidosis (hATTR), is an antisense drug designed specifically to reduce the production of transthyretin (TTR). If approved, the drug would provide a significant improvement in safety and effectiveness of the treatment, prevention, or diagnosis of this serious uncommon condition.

The FDA has set a Prescription Drug User Fee Act (PDUFA) date of July 6, 2018.

hATTR is a severe, life-threatening genetic disease, resulting from a misfolding of TTR proteins, causing a deposition of amyloid fibrils in various organs, like the peripheral nerves, heart, gastrointestinal system, eyes, kidneys, central nervous system (CNS), thyroid, and bone marrow. The buildup of TTR fibrils in patients with ATTR interferes with the intended functionality in the tissues and organs, leading to increased damage, a poor quality of life, and eventually death.

Today’s announcement was the result of data from a completed Phase 3 study (NEURO-TTR) of inotersen in patients with polyneuropathy due to hATTR. In it, oth primary endpoints — Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QoL-DN) and modified Neuropathy Impairment Score +7 (mNIS+7) – were met, and patients who were administered the drug experienced a clinical benefit much more favorable than patients who received placebo. 47% of all patients experienced improved or stable SF-36 physical component scores.

During the study, however, 2 safety issues arose: thrombocytopenia and serious renal adverse events (AEs). These complications aside, the most common AEs included nausea, chills, vomiting, and anemia.

"We have been working closely with both the FDA and the EMA following the completion of our Phase 3 study to expedite the regulatory review timelines for inotersen," said Brett Monia, Ph.D., senior vice president of drug discovery and franchise leader for oncology and rare diseases at Ionis Pharmaceuticals in a press release. "Today's outcome reflects our strong relationship with regulators and the quality and completeness of our regulatory submissions. It also reflects the potential for inotersen to serve a major unmet medical need based on the results of our Phase 3 study, which demonstrated early and sustained benefit to patients treated with inotersen in multiple aspects of their disease, including quality of life."

If inotersen is approved, the company has stated that it is prepared to promptly launch the drug in the U.S. and EU.

"Receiving Priority Review in the U.S. and Accelerated Assessment in the EU for inotersen shows that the regulatory agencies recognize the high unmet need and the urgency to identify effective therapies to treat patients with this devastating disease," said Sarah Boyce, chief business officer of Ionis Pharmaceuticals.

Inotersen was previously granted Orphan Drug Designation and Fast Track Status by the FDA. A Marketing Authorization Application (MAA) has been submitted to the European Medicines Agency (EMA), which has granted Accelerated Assessment and Orphan Drug Designation to inotersen for the treatment of patients with ATTR.

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