• Changes in familial amyloid polyneuropathy and polyneuropathy disability were significant
• Earlier indirect comparison of patisiran vs rival indicated patisiran superiority

Alnylam Pharmaceuticals, Inc.  presented new analyses from the APOLLO Phase 3 study of patisiran, an investigational RNAi therapeutic for the treatment of hereditary ATTR (hATTR) amyloidosis, in six presentations at the 2018 Peripheral Nerve Society (PNS) Annual Meeting being held July 22-25, in Baltimore, MD.

“We are pleased to continue to share new analyses from the APOLLO Phase 3 study with six presentations at the PNS annual meeting. We believe the new data presented underscore the potential clinical benefit of patisiran for patients with hATTR amyloidosis. First, the results of the exploratory EQ-5D-5L and EQ-VAS assessments show that patisiran treatment, relative to placebo, may help patients maintain or improve mobility and independence, reduce anxiety and depression, and favorably impact overall health status,” said Eric Green, Vice President and General Manager, TTR Program at Alnylam. “Further, we believe the results of an indirect analysis between patisiran and tafamidis highlight the therapeutic potential of patisiran, if approved. Finally, with patients on placebo experiencing substantial worsening in neuropathy in as little as nine months and irrespective of baseline disease severity, our new analyses show a clear need to intervene early in the course of this disease.”

Overall health status was an exploratory endpoint assessed in APOLLO using EuroQOL-5-dimension 5-level (EQ-5D-5L), a standardized measure of health status based on five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression, and the EuroQOL visual analogue scale (EQ-VAS), a measure of a patient’s global impression of their overall health as evaluated on a scale of zero (worst possible health) to 100 (best possible health). At 18 months, a larger proportion of patients on patisiran than placebo, respectively, showed preservation (defined as no change in score) or improvement relative to baseline in each EQ-5D-5L domain: mobility, 70 versus 22 percent; self-care, 66 versus 21 percent; usual activities, 72 versus 25 percent; pain/discomfort, 73 versus 31 percent; anxiety/depression, 81 versus 45 percent. Overall health, as measured by EQ-VAS, improved by an average of 2.4 points in patients on patisiran, while declining by an average of 7.1 points in placebo patients, indicating a 9.5 point difference (nominal p value less than 0.001).

FAP (familial amyloid polyneuropathy) Stage and PND score are commonly used to indicate neuropathy severity in hATTR amyloidosis and are based largely on ambulatory ability (e.g. whether, and how many, walking aids are required). It was shown that following 18 months of treatment, a greater proportion of patisiran patients compared to placebo showed stable or improved FAP Stage (79 versus 44 percent) and PND score (73 versus 30 percent). Improvements in FAP Stage and PND score were only seen with patisiran, and worsening occurred twice as frequently with placebo compared to patisiran. The observed changes in FAP Stage and PND score were statistically significant (p=9.5 x 10-8 and p=1.3 x 10-10, respectively), and further support the clinical benefit of patisiran compared to placebo in improving or preserving ambulation.

In articles published earlier in July of this year, patisiran results seemed to dominate those of a rival drug, inotersen. The comparison was not apples-to-apples, however.