Tegsedi (inotersen) continues to slow progression of familial amyloid polyneuropathy (FAP) and maintains the same safety profile over two years of treatment, results of an open-label extension study show.
A greater efficacy of the treatment was seen if it had been initiated early, and no new safety signals were reported with long-term use, according to a press release.
The data were presented at the 2019 American Academy of Neurology (AAN) Annual Meeting this month in Philadelphia, in a presentation titled “Long-Term Efficacy and Safety of Inotersen for Hereditary Transthyretin Amyloidosis: NEURO-TTR Open-Label Extension 2-Year Update (S27.008).”
“The long-term results from the NEURO-TTR open-label extension study are very encouraging as they demonstrated sustained improvements in neuropathy progression and quality of life compared to the natural history with greater improvements in both measures when starting Tegsedi earlier,” said Thomas Brannagan, director of the Peripheral Neuropathy Center at Columbia University Medical Center.
Familial amyloid neuropathy (FAP), also called hereditary transthyretin amyloidosis (hATTR), is marked by the aggregation of transthyretin (TTR) protein into amyloid fibrils that build up in tissues, particularly those of the nerves and heart, to cause symptoms of the disease.
Tegsedi, marketed by Ionis Pharmaceuticals and its subsidiary Akcea Therapeutics, is an antisense medication designed to suppress the production of TTR in the liver, the organ responsible for producing most of the protein.
The randomized, placebo-controlled NEURO-TTR Phase 2/3 trial (NCT01737398), now completed, showed that Tegsedi given under the skin (subcutaneously) over 15 months was able to delay nerve cell damage and improve the quality of life of FAP patients, compared with placebo.
The benefits were seen regardless of disease stage, heart involvement (cardiomyopathy), and type of underlying mutation. The most commonly reported side effects were kidney disease (glomerulonephritis) and low platelet counts (thrombocytopenia), both of which could be managed with closer monitoring.
Patients who completed NEURO-TTR, both in the placebo and Tegsedi groups, were offered the chance to enroll in a long-term, phase 3, open-label extension study (NCT02175004), which is ongoing and whose latest results were presented at the AAN meeting.
Of the 139 patients who completed the trial, nearly all (97%) decided to continue into the extension study, which continued for up to two years (104 weeks).
Patients were mostly men (69.4%), and had both polyneuropathy and cardiac involvement (65.7%).
At the beginning of the extension study, 61.9% of the patients could walk without assistance, 35.1% required a walking aid, and 3.0% were unable to walk.
The data showed that Tegsedi substantially reduced TTR protein levels 75% to 79% below the levels present when patients started treatment. These reductions were sustained throughout the study.
Among those who initiated Tegsedi as part of the extension study (switched from placebo), nearly 50% experienced improvements in neurological disease progression and over 40% experienced a better quality of life, compared with the predicted outcomes if they were to have continued on placebo.
At six months, patients who initiated Tegsedi as part of the extension study (switched from placebo) demonstrated a slowing of neurologic disease progression (measured by the modified Neuropathy Impairment Score +7, or mNIS+7) and improvements in quality of life (measured by Norfolk Quality of Life Questionnaire-Diabetic Neuropathy score, or Norfolk QOL-DN).
Those who had received the therapy for more than two years — 15 months in NEURO-TTR plus 12 months in the extension study — also continued to show benefit.
Researchers also saw that patients who started Tegsedi earlier had a greater benefit, both in terms of symptom progression and quality of life.
No new safety signals were observed and there were no signs of increased risk seen for life-threatening low platelet counts (thrombocytopenia) or severe kidney events with long-term use.
“For patients with hereditary ATTR amyloidosis, a late diagnosis or delayed treatment can be devastating as the disease can quickly progress, leading to worsening symptoms, significant disability and a deteriorating quality of life,” said Sarah Boyce, president of Akcea.
Brett P. Monia, Ph.D., chief operating officer of Ionis Pharmaceuticals, said: “We believe the NEURO-TTR [open-label extension] data continue to demonstrate a favorable benefit-risk profile for Tegsedi to treat patients with this devastating disease. Patients treated with Tegsedi continue to experience improvements in measures of neuropathy and quality of life, regardless of when treatment is initiated but with greater effects tied to earlier treatment initiation.”