Key result
Optimized muvalaplin synthesis boosts yield ~41% over the original discovery route.
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The development of a scalable, optimized synthesis process for muvalaplin ensures clinical supply and lays the foundation for commercial production.
Herein, we describe the development of steps 5–7 for a large-scale process to synthesize muvalaplin, a small-molecule lipoprotein(a) inhibitor for the potential reduction of major adverse cardiovascular events in participants with established cardiovascular disease or at risk for a first cardiovascular event. Each step was optimized, leading to improvements in safety, robustness, and cost of goods that ultimately resulted in a 41% yield increase over three steps and a 60% reduction in PMI compared to the original discovery synthesis. The process was safely scaled to >100 kg, thus ensuring clinical supply and laying the foundation for a commercial route.
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Walker et al. (2026) studied Cardiovascular disease (target indication). Optimized synthesis process (steps 5-7) for muvalaplin vs. Original discovery synthesis was evaluated on Yield increase and process mass intensity (PMI) reduction. Optimization of the synthesis process for muvalaplin resulted in a 41% yield increase over three steps and a 60% reduction in process mass intensity compared to the original discovery synthesis.
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