AstraZeneca Invests $100M in Oral Lp(a) Drug for Cardiovascular Disease

AstraZeneca has made a significant move in the cardiovascular drug market by licensing YS2302018, a preclinical drug from CSPC Pharmaceutical Group, based in Hong Kong. The agreement includes an upfront payment of $100 million, with the potential for CSPC to receive up to $1.92 billion if the drug reaches development and commercialization milestones. Additionally, CSPC will earn royalties from the sales of the commercialized product.

YS2302018 is being developed to treat dyslipidemia, a condition characterized by abnormally high cholesterol levels in the blood. One key indicator of this condition is elevated levels of lipoprotein (a), or Lp(a), a protein that transports cholesterol through the bloodstream. Elevated Lp(a) levels are associated with an increased risk of cardiovascular diseases, such as coronary artery disease and stroke, due to the buildup of cholesterol in blood vessel walls.

Currently, there are therapies available that lower Lp(a) levels indirectly by targeting PCSK9, a liver protein that regulates cholesterol. Drugs like Amgen's Repatha and Regeneron Pharmaceuticals' Praluent, both approved PCSK9 inhibitors, have been shown to reduce Lp(a) levels. Additionally, Novartis’s siRNA therapy, Leqvio, also reduces Lp(a) by silencing the gene responsible for producing PCSK9. However, these therapies are administered via injections and do not target Lp(a) directly.

AstraZeneca’s YS2302018 stands out because it is an oral Lp(a) disruptor, offering the convenience of once-daily oral dosing compared to injectable alternatives. This formulation positions AstraZeneca to compete more effectively in the dyslipidemia treatment market, particularly against Eli Lilly. Lilly's muvalaplin, an oral small molecule disruptor of Lp(a), is currently in Phase 2 trials.

Besides Lilly, other companies are also developing siRNA therapies aimed at reducing Lp(a) levels. Lilly's lepodisiran is in a Phase 3 clinical trial for atherosclerotic cardiovascular disease. Amgen’s olpasiran is in Phase 3 testing for the same indication, while Silence Therapeutics is preparing for pivotal trials with its candidate, zerlasiran. Ionis Pharmaceuticals’ antisense oligonucleotide, pelacarsen, intended to reduce Lp(a) production, is in Phase 3 testing through a partnership with Novartis.

AstraZeneca's portfolio of cardiovascular, renal, and metabolism drugs includes blockbuster products like Farxiga, used for type 2 diabetes, heart failure, and chronic kidney disease, and Brilinta, for acute coronary syndromes. The company believes that YS2302018 could have applications across a broad range of cardiovascular diseases. It could be used as a standalone treatment or in combination with other therapies.

One such combination could involve AstraZeneca’s own PCSK9 inhibitor, AZD0780. In May, AstraZeneca reported promising Phase 1 results for AZD0780, which showed a 52% reduction in LDL cholesterol levels when taken once daily alongside statin therapy. The drug was well tolerated, with no serious adverse events reported. AZD0780 is currently undergoing Phase 2 trials, with a targeted enrollment of 428 participants.

Sharon Barr, AstraZeneca's executive vice president and head of biopharmaceuticals R&D, emphasized the importance of developing novel therapies for cardiovascular disease, a leading global cause of death. She noted that advancing treatments that can effectively address known risk factors either alone or in combination with other therapies is a crucial part of AstraZeneca's strategy to improve patient care.