Results for Patisiran in TTR-Mediated Amyloidosis

Alnylam Pharmaceuticals announced new clinical data for patisiran (ALN-TTR02), an RNAi therapeutic targeting transthyretin (TTR) being developed for the treatment of TTR-mediated amyloidosis (ATTR). Updated results from its Phase 2 study in 29 patients with Familial Amyloidotic Polyneuropathy (FAP) confirmed the robust TTR knockdown of up to 96%, with a mean knockdown of approximately 80% with the use of patisiran.

Patients included in the Phase 2 study were then randomized to an open-label extension (OLE) study, evaluating the long-term safety and tolerability of patisiran. The OLE study measured a number of clinical endpoints every six months, including the modified composite Neuropathy Impairment Score (mNIS+7); this score is also the primary endpoint of the Phase 3 APOLLO trial of patisiran in FAP. Serum TTR levels were measured following the first dose and then pre-dose every 6–12 weeks. Preliminary results from the OLE study demonstrated that multiple doses of patisiran achieved sustained knockdown of serum TTR protein levels at the 80% target level through 168 days.

RELATED: Phase 2 Stem Cell Study for ALS Approved

Alnylam also presented results from a natural history, cross-sectional analysis study of 283 FAP patients aimed at measuring the rate of neuropathy progression and its correlation with disease severity. The analysis showed a change in the NIS rate of 14.3 points per year. Results demonstrated that NIS is highly correlated with Polyneuropathy Disability (PND) Score (p<0.0001 by ANOVA) and FAP Stage (p<0.0001 by ANOVA). NIS was also shown to be associated with TTR genotype, with the early-onset V30M population exhibiting a significantly lower median NIS compared to late-onset V30M or non-V30M patients (p<0.001).

The results of the natural history study provide a foundation for the conduct of the ongoing Phase 3 APOLLO trial of patisiran, designed to establish the efficacy and safety of patisiran in ATTR patients with FAP.

For more information call (617) 551-8200 or visit