Arrowhead prioritizes lead RNAi heart drug, deprioritizes others

Arrowhead Pharmaceuticals is streamlining its cardiometabolic pipeline, shifting its focus to the development of plozasiran and seeking a partner for zodasiran. This strategy comes as Arrowhead readies plozasiran for a Phase III cardiovascular outcomes trial. Plozasiran, an RNA interference (RNAi) therapeutic, aims to reduce apolipoprotein-CIII (ApoC3) levels and has displayed promising outcomes in clinical studies involving three patient groups: familial chylomicronaemia syndrome (FCS), severe hypertriglyceridaemia, and mixed hyperlipidaemia.

Recently, Arrowhead shared positive top-line results from the Phase III PALISADE study, which assessed plozasiran in FCS patients. The trial achieved its primary goal of lowering triglycerides (TG) and met all key secondary objectives, including decreasing the incidence of acute pancreatitis compared to a placebo.

At its recent R&D day, Arrowhead presented additional data from PALISADE. The study revealed significant placebo-adjusted median TG reductions of -80% and -78% at month 10 with quarterly dosages of 25 mg and 50 mg, respectively. Arrowhead demonstrated that plozasiran, administered every three months, maintained consistent median and mean triglyceride levels throughout the study period with minimal variability. Chief Medical Scientist Bruce Given highlighted that this consistency underscores the therapeutic's potential.

Arrowhead also shared detailed safety data, showing comparable incidences of treatment-emergent adverse events (AEs) between the placebo and active groups. Notably, the placebo group experienced a slightly higher rate of serious and severe AEs. Analysts at Morgan Stanley found these updates encouraging and Arrowhead plans to present the full dataset at an upcoming scientific conference.

In tandem with these promising results, Arrowhead is gearing up for a Phase III cardiovascular outcomes trial named CAPITAN, which will further investigate plozasiran in a broader patient population. This study will include patients with mixed hyperlipidaemia and residual risk of atherosclerotic cardiovascular disease.

Regarding zodasiran, which targets ANGPTL3, Arrowhead acknowledged that although the data to date has been "highly encouraging" and merits further Phase III investigation, advancing this candidate will necessitate collaboration. Bruce Given explained that, based on comprehensive evaluations and resource considerations, Arrowhead has decided to advance plozasiran independently. Further development of zodasiran will only proceed if a suitable partner for development and commercialization is identified.