Davide Adams (France)
Université Paris-Saclay, U1195, INSERM Department of NeurologyAuthor Of 2 Presentations
GLOBAL OPEN-LABEL EXTENSION: 24-MONTH DATA OF PATISIRAN IN PATIENTS WITH HATTR AMYLOIDOSIS
- Marco Luigetti (Italy)
Abstract
Background and Aims:
Hereditary transthyretin-mediated (hATTR) amyloidosis, is a progressive, life-threatening disease. Patisiran’s efficacy/safety have been demonstrated in Phase 2 and 3 studies in patients with hATTR amyloidosis with polyneuropathy. Interim 24-month efficacy/safety analyses of the ongoing Global OLE study are described.
Methods:
Multicenter, international, OLE, safety/efficacy study (NCT02510261) in patients who completed parent studies, including patients in the Phase 3 APOLLO randomized to placebo (n=49) or patisiran (n=137) over 18 months and patients in the Phase 2 OLE (n=25) receiving patisiran over 24 months.
Results:
178/211 patients enrolled in the Global OLE had at least 24 months of exposure as of October 7, 2019. Safety profile remained consistent with previous studies. After 24 months of additional patisiran treatment, durable improvement was seen for mNIS+7 (mean change [SEM]) in APOLLO/patisiran (-4.9 [2.1]) and Phase 2 OLE (-5.9 [2.1]) groups compared to their parent study baselines. Norfolk QOL-DN continued to show durable improvement in APOLLO/patisiran patients (-2.4 [2.4]). APOLLO/placebo patients experienced halting of disease progression and QOL improvement compared to Global OLE baseline after 24 months of patisiran (mNIS+7: +0.1 [3.3], Norfolk QOL-DN: -4.1 [3.3]), although they had progressed relative to APOLLO baseline (mNIS+7: +26.3 [5.0], Norfolk QOL-DN: +15.8 [4.5]) given the progression while on placebo.
Conclusions:
In the Global OLE, patisiran continue to demonstrate long-term durable efficacy. Despite marked progression on placebo during APOLLO, previously untreated patients continue to exhibit halting of disease progression and QOL improvement following 24 months of patisiran. Patisiran continues to demonstrate a positive benefit:risk profile.
HELIOS-A: 9-MONTH RESULTS FROM THE PHASE 3 STUDY OF VUTRISIRAN IN PATIENTS WITH HEREDITARY TRANSTHYRETIN-MEDIATED AMYLOIDOSIS WITH POLYNEUROPATHY
- Laura P. Obici (Italy)
Abstract
Background and Aims:
Hereditary transthyretin-mediated (hATTR) amyloidosis, also known as ATTRv amyloidosis, is a progressive disease caused by misfolded transthyretin (TTR) that accumulates as amyloid fibrils in multiple tissues and organs. Vutrisiran, an investigational RNAi therapeutic for the treatment of ATTR amyloidosis, targets variant and wild-type TTR.
Methods:
HELIOS-A (NCT03759379) is a Phase 3, global, open-label study of vutrisiran 25 mg SC every 3 months in patients with ATTRv amyloidosis with polyneuropathy,randomized (3:1) to vutrisiran or patisiran, a reference comparator RNAi therapeutic approved for hATTR amyloidosis with polyneuropathy. Randomization was stratified by TTR genotype (V30M vs. non-V30M) and baseline NIS score (<50 vs ≥50). The APOLLO placebo arm (N=77) serves as external control for the primary and most secondary endpoints. Month 9 efficacy analyses include change from baseline in mNIS+7 (primary endpoint), Norfolk QOL-DN (secondary), and 10-meter walk test (10-MWT) (secondary), compared to APOLLO placebo arm.
Results:
HELIOS-A enrolled 164 patients (122 [74.4%] vutrisiran, 42 [25.6%] patisiran). Vutrisiran met the primary endpoint (p<0.001) and achieved statistical significance (p<0.001) for all planned secondary endpoints. The majority of patients showed improvement in neurologic impairment and quality of life relative to baseline. Vutrisiran demonstrated an acceptable safety profile; most common adverse events in vutrisiran-treated patients occurred at similar or lower rate versus the APOLLO placebo arm.
Conclusions:
The 9-month primary analysis demonstrates that vutrisiran improves neuropathy and QOL in patients with ATTRv amyloidosis with polyneuropathy. HELIOS-A will continue to investigate the efficacy and safety of vutrisiran through the 18-month treatment and extension periods.