Ionis Pharmaceuticals’ inotersen (IONIS-TTR Rx) continues to demonstrate sustained, long-term benefit for patients with familial amyloid polyneuropathy (FAP), also known as hereditary ATTR (hATTR) amyloidosis.
Recent positive results of a study were the subject of several presentations at the 16th International Symposium on Amyloidosis (ISA) being held March 26-29 in Kumamoto, Japan. Details about the presentations are available here.
The NEURO-TTR study (NCT01737398) has demonstrated that 300 mg of inotersen once weekly could effectively improve quality of life and reduced symptoms of neuropathy in FAP patients with cardiac disease. In addition, upon 15 months of treatment, patients reported feeling and functioning better compared to study participants treated with placebo.
Patients with significant cardiac disease at the beginning of the study also showed significant improvements in several cardiac measures, including reduction of in left ventricle mass and of the ventricular septum, and increased posterior wall thickness.
Inotersen also has demonstrated it can significantly reduce the levels of TTR, the widely recognized hallmark of FAP. Almost 90% of patients achieved a TTR reduction of more than 50%, and about 50% of patients had more than 75% TTR reduction at 15 months of treatment. These TTR reductions were associated with improvements of 50% in quality of life and of 37% in neuropathy symptoms, compared to baseline.
In addition to these findings, the ongoing NEURO-TTR open-label extension trial (NCT02175004) continues to demonstrate the clinical benefit of long-term treatment with the drug.
Patients treated for up to a total of 27 months continue to experience improved quality of life and reduced nerve damage progression. Also, patients who were treated initially with placebo during the NEURO-TTR trial and then began inotersen therapy in the trial extension period showed significant and sustained improvements.
“I’m encouraged that inotersen-treated patients in the [open-label extension trial] continue to experience robust and sustained benefits in quality of life and measures of neuropathy impairment,” John L. Berk, MD, said in a press release. Berk is associate professor of medicine at Boston University School of Medicine and a principal investigator in the NEURO-TTR study.
“The rapid and sustained benefits observed with inotersen in the NEURO-TTR and [open-label extension trial] studies illustrate the substantial potential of inotersen to change the course of this devastating disease,” Berk added.
Upon median treatment duration of 692 days, five fatal adverse events occurred during the extension trial, but none were considered to be related to inotersen treatment. Of 161 participants, 33 reported serious adverse events, of which three were considered to be related to the treatment.
An ongoing investigator-sponsored Phase 2 trial (NCT02627820) also is evaluating the impact of inotersen in cardiac disease patients with FAP.
As of January 2018, the trial has showed that all 10 patients showed a mean reduction of 8.5% in left ventricular mass upon two years of treatment. In addition, eight patients improved their physical capacity, as demonstrated by improved 6-minute walk test (6-MWT) by 29 meters and 41 meters at 1 and 2 years of treatment compared to baseline.
“Our commitment to patients with ATTR amyloidosis goes beyond those with the hereditary form of the disease. This highly potent LICA drug offers the potential for monthly or less frequent subcutaneous administration with very low doses,” said Brett P. Monia, chief operating officer and senior vice president of antisense drug discovery and translational medicine at Ionis Pharmaceuticals. “We and Akcea plan to advance AKCEA-TTR-LRx into clinical studies later this year.”