IONIS-TTRRx Shows Significant Benefit in Phase 3 hATTR Study

Positive data from a Phase 3 study of inotersen (IONIS-TTRx) in patients with hereditary ATTR amyloidosis (hATTR) was presented at the 2018 American College of Cardiology (ACC) Annual Meeting.

Key quality of life data from Ionis Pharmaceuticals’ Phase 3 study was shown in the poster Inotersen Improves Quality of Life in Patients with Hereditary Transthyretin Amyloidosis with Polyneuropathy and Cardiomyopathy: Results of the Phase 3 Study Neuro-TTR by Matthew S. Maurer, M.D., Medical Director, HCM Center at New York-Presbyterian Hospital/Columbia University Medical Center.

The data highlighted the improvement in quality of life (QOL) and functional capacity experienced by 50% of treated with the investigational antisense drug.

Neuro-TTR demonstrated significant benefit compared to placebo in patients with cardiac disease at baseline 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. It was shown that half of patients receiving IONIS-TTRx were more capable of completing daily activities than they were at the start of the study, and these benefits were significant, early and sustained across patient types.

“Significant improvements in Norfolk QOL-DN and SF-36, which include several domains related to patient well-being and activities of daily living, suggest that inotersen improves the QOL of patients with hATTR-PN who have the greatest disease burden, those with CM,” it was concluded in the abstract, which was recently published in the Journal of the American College of Cardiology.

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

IONIS-TTRx has been designed specifically to reduce the production of transthyretin (TTR). If approved, the drug would provide a significant improvement in safety and effectiveness of the rare genetic condition. In January, almost exactly 2 months after Inonis submitted its new drug application (NDA) to the U.S. Food and Drug Administration (FDA), it was announced that Priority Review had been granted.

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.

The FDA has set a Prescription Drug User Fee Act (PDUFA) date of July 6, 2018. If inotersen is approved, the company has stated that it is prepared to promptly launch the drug in the U.S. and EU.

At the time of this writing, there are 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.

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