AstraZeneca Bets $2B on Preclinical Heart Disease Drug

AstraZeneca has struck an exclusive licensing agreement with CSPC Pharmaceutical Group, a Chinese company, to advance a preclinical lipid-lowering drug aimed at addressing dyslipidemia-related conditions. The deal, announced on Monday, involves AstraZeneca paying $100 million upfront and up to $1.92 billion in regulatory and commercial milestones. CSPC will also receive tiered royalties if the drug reaches the market.

The partnership allows AstraZeneca to develop YS2302018, an investigational oral small molecule disruptor of lipoprotein (a) (Lp(a)). Lp(a) is a type of LDL cholesterol linked to higher risks of heart attack and stroke, particularly in patients with a history of cardiovascular issues. According to the Centers for Disease Control and Prevention (CDC), current treatments for high Lp(a) levels are limited, with apheresis being the only FDA-approved intervention. While exercise and a healthy lifestyle can help manage LDL cholesterol, they do not directly lower Lp(a).

Sharon Barr, head of BioPharmaceuticals R&D at AstraZeneca, emphasized the significance of CSPC’s Lp(a) blocker, calling it an "important addition" to AstraZeneca’s cardiovascular pipeline. She highlighted the drug's potential to help patients better manage dyslipidemia and related cardiometabolic diseases. The pharmaceutical giant plans to explore the development of YS2302018 either independently or in combination with its experimental PCSK9 blocker, AZD0780, for various cardiovascular conditions.

AstraZeneca is not alone in the Lp(a) drug development field. Eli Lilly, for instance, has made considerable strides with its investigational oral Lp(a) inhibitor, muvalaplin. In August 2023, Lilly released Phase I data showing that muvalaplin achieved maximum placebo-adjusted reductions in Lp(a) levels by 63% to 65%, with over 90% of treated participants reaching Lp(a) levels below 50 mg/dL. Muvalaplin has now advanced to Phase II development focused on cardiovascular diseases.

Besides muvalaplin, Lilly is also developing lepodisiran, an experimental siRNA therapeutic designed to target the LPA gene responsible for Lp(a) production. This drug is being investigated for its potential in treating atherosclerotic cardiovascular disease.

Novartis and Ionis Pharmaceuticals have also entered the Lp(a) therapeutic space with their antisense therapy pelacarsen. Pelacarsen works by lowering circulating Lp(a) levels through the suppression of apolipoprotein(a) production in the liver. The drug is currently in the late stages of development, aimed at preventing cardiovascular events in patients with high Lp(a) levels.

With the CSPC deal, AstraZeneca aims to enhance its portfolio of cardiovascular treatments. The collaboration is part of a wider trend in the pharmaceutical industry, where companies are increasingly focusing on innovative therapies to address unmet medical needs in cardiovascular health.