Lancet Neurology: Patisiran treats the long-term safety and effectiveness of multiple neuropathic amyloid changes mediated by hereditary thyroxine delivery proteins

Genetic thyroxine carries protein-mediated amyloid degeneration, also known as ATTRv amyloid degeneration, which is a rare hereditary carrying disease.
the lesions are caused by mutations in the thyroxine delivery protein (TTR) gene, which cause TTR to fold incorrectly and accumulate into amyloid deposits in multiple organs and tissues (somatic and autonomous nerves, heart, etc.).
patients developed a mixture of multiple neuropathy and cardiomyopathy and showed rapid progress after clinical onset.
the medium survival of untreated patients was 4.7 years after diagnosis, while that of patients with cardiomyopathy was 3.4 years.
risk factors for poor prognosis for the disease include advanced multiple neuropathy, non-Val30Met (also known as p.Val50Met) genotype delayed disease (50 years of age) and heart damage.
such as in-place liver transplantation and TTR stabilizers may slow the natural progression of the disease in the early stages, but the deterioration of neurologic function and quality of life (QOL) in patients is often observed.
study focused on assessing the safety and effectiveness of Patisiran( an RNA interference therapy that inhibits TTR production) for long-term treatment of patients with multiple neuropathy mediated by hereditary thyroxine delivery proteins.
the multi-center, Open Label Extension (OLE) trial recruited patients to 43 hospitals or clinical centres in 19 countries.
patient is eligible if he or she has completed the APOLLO Phase 3 or OLE Phase 2 study and is resistant to the study drug.
eligible patients from the APOLLO (Patisiran and placebo groups) and Phase 2 OLE (Patisiran group) study participated in the global OLE trial.
of the 212 eligible patients, 211 were selected: 137 patients in the APOLLO-Patisiran group, 49 patients in the APOLLO-placebo group and 25 patients in the OLE-Patisiran Phase 2 group were intravenously injected with Patisiran 0.3 mg/kg or placebo every 3 weeks and are scheduled to last for 5 years.
Its efficacy assessment includes measurements of multiple neuropathy (improved neuropathic damage score of 7 (mNIS)), quality of life, autoigenic symptoms, nutritional status, disability, walking condition, motor function, and heart pressure.
current findings are based on an interim analysis of patients who had completed a 12-month efficacy assessment by the data cut-off date.
as of September 24, 2018, 126 (92%) of the 137 patients in the APOLLO-Patisiran group had completed the 12-month assessment, 38 (78%) of the 49 patients in the APOLLO-placebo group (78%) had completed the assessment, and 25 (100%) of the 25 patients in the OLE-Patisiran 2 group had completed the assessment.
At 12 months, the improvement in patients with mNIS-7 continued from the study baseline to global OLE treatment (average change in patients in the APOLLO-Patisiran group -4.0, 95 % CI -7.7 to 0.3; OLE-Patisiran Phase 2 - 4.7, 95 % CI - 11.9 to 2.4).
total, 204 (97%) of the 211 patients reported adverse events, 82 (39%) reported serious adverse events and 23 (11%) died.
the rate of serious adverse events in the APOLLO-placebo group (28 out of 49 (57%) was higher than in the APOLLO-Patisiran group (48 out of 137 (35%) or OLE-Patisiran 2 (6 out of 25 ( 24%)).
summary, the overall results of the 12-month mid-term data analysis of the global OLE study showed that Patisiran had ongoing benefits for patients with multiple neuropathic amyloid changes mediated by hereditary thyroxine delivery proteins.
the current data also highlight the importance of Patisiran's early treatment in the course of the disease to prevent or reverse the progression of multiple neuropathy, autoigenic neurological disorders, disability, malnutrition and QOL.
Adams, DavidVita, Giuseppe et al. Long-term safety and efficacy of patisiran for hereditary transthyretin-mediated amyloidosis with polyneuropathy: 12-month results of an open-label extension study. The Lancet Neurology, Volume 20, Issue 1, 49 - 59 Network Source: Web Copyright Notice: All text, images and audio and video materials on this website that indicate "Source: Met Medical" or "Source: MedSci Original" are owned by Mets Medicine and are not authorized to be reproduced by any media, website or individual, and are authorized to be reproduced with the words "Source: Mets Medicine".
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