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Final 24-Month Results from Phase 2 OLE Study of Patisiran, in Development for hATTR Amyloidosis

We reported final 24-month results from our Phase 2 open-label extension (OLE) study of patisiran, an investigational RNAi therapeutic targeting transthyretin (TTR) for the treatment of hereditary ATTR (hATTR) amyloidosis. These data were presented at the American Academy of Neurology (AAN) 2017 Annual Meeting in Boston, Massachusetts.



Final results (N=26) from the Phase 2 OLE study showed a mean decrease in the modified neuropathy impairment score (mNIS+7) of 7.0 points at 24 months, providing continued evidence that patisiran has the potential to halt or improve neuropathy progression in patients with hATTR amyloidosis. In a new post-hoc analysis exploring the relationship between baseline neuropathy severity and change in mNIS+7, the potential effect of patisiran was observed across the full range of disease severity, including patients with a high degree of neurologic impairment at baseline (N=9 with baseline NIS of 46-93 points). Moreover, in the first post-hoc exploratory analysis of its kind, patisiran administration was found to be associated with statistically significant decreases in TTR amyloid deposition as measured from blinded analysis of skin biopsy samples from the distal thigh and distal leg. This decrease in mean dermal amyloid content is consistent with the statistically significant mean increase in sweat gland nerve fiber density observed in the same skin biopsy samples over 24 months. Taken together, these exploratory analyses support the therapeutic hypothesis that reduction of mutant and wild-type TTR can potentially lead to reduction of TTR amyloid deposition and increased nerve regeneration.

Patisiran administration was found to be generally well tolerated in patients with hATTR amyloidosis out to 25 months, with no drug-related serious adverse events (SAEs) reported. Drug-related or possibly drug-related adverse events (AEs) in four or more patients were flushing (22.2%) and infusion-related reactions (22.2%), all of which were mild in severity and did not result in any discontinuations. There were ten reports of serious adverse events (SAEs) in seven patients, all of which were unrelated to study drug, including two previously reported deaths. There were no clinically significant changes in liver function tests, renal function, or hematologic parameters, including platelets.

We believe patisiran has the potential to halt or improve neuropathy progression and provide an important treatment option for the management of hATTR amyloidosis, a devastating disease with enormous unmet medical need. We are committed to serving the hATTR amyloidosis community, and we look forward to the continued advancement of patisiran as we strive to improve the lives of patients, their families, and caregivers.