Patisiran and Inotersen Continue to Show Efficacy and Safety in Open-Label and Expanded-Access Trials for Patients With Hereditary Transthyretin-Mediated Amyloidosis


Results from an open-label extension of the multi-center, randomized, double-blind phase 3 APOLLO study (NCT01960348) of patisiran (Onpattro; Alnylam, Cambridge, MA) and from the NEURO-TTR study (NCT01737398) of inotersen (Tegsedi; Akcea Therapeutics, Boston, MA) for treatment of patients with hereditary transthyretin-mediated (hATTR) amyloidosis were presented at the American Association of Neuromuscular and Electrodiagnostic Medicine (AANEM) in Washington, DC Oct 10-12. 

Patisiran and inotersen are RNA-interference therapies approved for the treatment of patients with hATTR with neuropathy. Inotersen is administered subcutaneously and patisiran is administered intravenously. 

In the NEURO-TTR study, 172 patients with hATTR amyloidosis with neuropathy were randomly assigned to receive inotersen (n = 112) or placebo (n = 60). Patients treated with inotersen had significant improvements in neuropathy and quality of life measures (New Engl J Med. 2018;379:22-39). In the open-label extension study, patients were followed for up to 66 months and 47% of patients improved or stabilized their neurologic function (P= .0005), muscle weakness (< .001), reflexes (= .04), sensory component (< .001), heat conduction (P = .025), and heat-pain (= .001). In the open-label extension trial, the key safety findings of 

thrombocytopenia and renal events were consistent with that seen in the placebo-controlled study and were monitorable and manageable.

In the APOLLO study, 225 patients with hATTR amyloidosis with neuropathy were randomly assigned to receive 0.3 mg/kg of patisiran (n = 148) or placebo (n = 77). Patients treated with patisiran had significant improvements in neuropathy, gait speed, and modified body-mass index compared to those treated with placebo (New Engl J Med.2018;379:11-21).

At 18 months, patients’ activities of daily living were measured with the Rasch-Built Overall Disability Scale (R-ODS) consisting of 24 items that are scored from 0-2 with higher scores corresponding to more impairment. Patients treated with patisiran had least-squares mean R-ODS scores that were 9 points lower than the mean score of patients given placebo (P = 4.07x10-16). Patients treated with patisiran had less difficulty reading a newspaper or book (31%) or standing for a long period of time (54%) compared to those given placebo (53% and 80%, respectively). 

In an open-label extension study, patients from this trial were evaluated regularly and interim results support the long-term safety and efficacy of treatment for up to 5 years. 

In the expanded access protocol (EAP), an open-label multicenter study (NCT02939820),  93 patients with genotype-confirmed hATTR amyloidosis and symptomatic polyneuropathy received patisiran 0.3 mg/kg IV every 3 weeks and had safety and efficacy similar to that seen in the randomized, double-blind APOLLO trial.


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