Arrowhead drops heart disease drug, focuses on another amid rising pipeline costs

Arrowhead Pharmaceuticals has made a strategic decision regarding its cardiometabolic disease pipeline, choosing to focus on plozasiran while deprioritizing zodasiran. Arrowhead, known for its expertise in RNA interference (RNAi) technology, is addressing its financial management by concentrating its efforts on the most promising candidate.

Both plozasiran and zodasiran are RNAi molecules aimed at enhancing cardiovascular health. Plozasiran targets APOC3, while zodasiran targets ANGPTL3, and both are designed to reduce harmful molecules such as triglycerides and lipoproteins that contribute to cardiovascular disease. Despite the potential of both drugs, the company has decided to advance only plozasiran.

Vincent Anzalone, the head of investor relations at Arrowhead, emphasized that the choice was driven by the positive attributes of plozasiran rather than any shortcomings with zodasiran. Plozasiran has shown impressive results in three different settings, suggesting that it could successfully launch across progressively larger indications, thereby supporting Arrowhead's commercial expansion plans.

The decision was also influenced by the current landscape of cardiovascular disease treatments. Bruce Given, M.D., Arrowhead’s chief medical scientist, explained that when the company initially considered focusing on APOC3 and ANGPTL3 around 2016-2017, the market lacked alternatives like PCSK9 inhibitors, the Regeneron antibody against ANGPTL3, and bempedoic acid. Now, there are numerous LDL cholesterol-lowering drugs available, creating significant competition.

However, the market for high triglycerides remains relatively underserved. Given highlighted that plozasiran could meet unmet needs across a broad spectrum of patients, from those suffering from pancreatitis to asymptomatic individuals with mixed hyperlipidemia or severe hypertriglyceridemia.

While Arrowhead is investing its resources in plozasiran, it is seeking a partner to advance zodasiran. Given expressed the need for a partner with sufficient resources and a robust commercial presence to compete effectively in the LDL cholesterol space. He believes that zodasiran has the potential to make a significant impact in this area, but acknowledges that Arrowhead currently lacks the capacity to fully develop and market the drug.

By focusing on plozasiran, Arrowhead aims to make substantial progress in its development. The company is moving forward with several trials, including a significant phase 3 cardiovascular outcomes study. This trial will primarily involve participants who have experienced a previous cardiovascular event, with a smaller group of participants who are at risk but have yet to experience such an event.

The strategic shift allows Arrowhead to allocate its resources more effectively, betting on the most promising candidate in its pipeline. If successful, plozasiran could be ready for market launch by 2025, positioning Arrowhead to meet significant unmet needs in the treatment of high triglycerides. In the meantime, the search for a suitable partner for zodasiran continues, with the hope that this candidate can also eventually make a meaningful contribution to cardiovascular health.