Abstract Details

Title Evaluation of Patisiran With Concomitant or Prior Use of Transthyretin Stabilizers

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) Neuromuscular and Clinical Neurophysiology (EMG) Posters (7:00 AM-5:00 PM)

Poster/Presentation
Number 085

Objective To describe the safety, PD and efficacy of patisiran in patients receiving TTR stabilizers

Background Hereditary transthyretin-mediated (hATTR) amyloidosis is a life-threatening disease caused by deposition of transthyretin (TTR) protein in multiple organs and tissues. Current pharmacological treatments include TTR stabilizers (tafamidis, diflunisal), which stabilize the TTR tetramer, and TTR silencing therapies (patisiran, inotersen), which reduce production of mutant and wild-type TTR.

Design/Methods Safety and pharmacodynamics (PD) of patisiran alone or with a concomitant TTR stabilizer from the 24-month Phase 2 Open-Label Extension study (OLE; NCT01961921) and safety and efficacy of patisiran in patients with or without prior TTR stabilizer use from the 18-month Phase 3 APOLLO study (NCT01960348) were evaluated

Results In the Phase 2 OLE (N=27), 7 patients (25.9%) took patisiran alone and 13 (48.1%) and 7 (25.9%) patients took patisiran with concomitant tafamidis or diflunisal, respectively. Median exposure was: 736 days for patisiran alone, patisiran with tafamidis 736 days, and with diflunisal 421 days. Safety profiles across concomitant TTR stabilizer groups were consistent with safety profiles of the respective therapies alone. Mean (standard error [SE]) serum TTR reduction over 24 months was similar, regardless of concomitant stabilizer use (83.4% [3.5], 81.8% [1.4], 81.3% [3.0]). At APOLLO baseline (N=225), 74 patients (32.9%) reported prior tafamidis use, 45 (20.0%) prior diflunisal use. Safety profile was consistent, regardless of prior TTR stabilizer use. At 18 months, mean (SE) improvement in mNIS+7 was seen across all patisiran-treated patients, regardless of prior stabilizer use (patisiran alone -3.4 [2.69], prior tafamidis -6.3 [2.41], prior diflunisal -2.8 [2.68]), while placebo-treated patients progressed on average.

Conclusions Evaluation of safety and PD data from a small cohort suggests that the PD profile of patisiran is unaffected by concomitant TTR stabilizer use. Additionally, these data indicate that patients benefit from patisiran treatment regardless of concomitant or prior use of TTR stabilizers.

Authors/Disclosures
Madeline Merkel PRESENTER	Madeline Merkel has received personal compensation for serving as an employee of Alnylam Pharmaceuticals.
	No disclosure on file
	No disclosure on file
Jing Marantz	No disclosure on file

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Abstract Details