Ionis Pharmaceuticals Inc. (IONS): SHTG approval, as expected; ARWR data in 3Q remains the focus

研报英文原文证据摘录

Ionis Pharmaceuticals Inc. (IONS): SHTG approval, as expected; ARWR data in 3Q remains the focus

Goldman Sachs Ionis Pharmaceuticals Inc. (IONS)

reduction. If serious hepatic injury with clinical symptoms and/or hyperbilirubinemia

or jaundice occurs, promptly discontinue TRYNGOLZA.

This section of the label also states that Tryngolza can cause increases in liver enzymes

and hepatic fat. On the latter, the label states: The clinical meaningfulness of these

findings remains uncertain. Management noted that the liver monitoring is not required

- the guidance to consider liver enzyme values at baseline and prior to dose escalation is

typical, in their view.

In the Ph3 studies, there was a statistically significant placebo-adjusted mean reduction

in fasting TGs of up to 72% (primary endpoint) as well as a statistically significant

reduction in acute pancreatitis (AP) events of 85% (p=0.0002), per the prespecified

analysis of pooled Tryngolza groups compared to pooled placebo groups across both

studies at 12 months. Specifically, the 80mg doses achieved a placebo-adjusted TG

reduction of 72% in CORE and 55% in CORE2, and the 50mg doses reached 63% and

49% at six months. On the AP data, the 85% reduction was based on a total of 22 events

in 17 patients in the placebo arm vs. seven events in five patients in the treated group.

IONS noted that the 85% reduction was from the pooled data, split 91%/76% from the

50mg/80mg doses.

On safety, hepatic fat fraction (HFF) has emerged as a key debate, where an increase was

observed at 12 months with Tryngolza (2.28 percentage points for Tryngolza 50mg; 4.18

percentage points for Tryngolza 80mg group; 0.14 percentage points in the placebo

group) - we see IONS’ presentation at NLA as supportive of a transient effect, as there