Muvalaplin

iStock, Robert Way For an exclusive license to the preclinical Lp(a) disruptor, AstraZeneca is paying CSPC Pharmaceutical Group $100 million upfront and offering up to $1.92 billion in regulatory and commercial milestones. AstraZeneca on Monday entered into an exclusive licensing deal with China-based CSPC Pharmaceutical Group to develop a preclinical lipid-lowering drug candidate, aiming to provide additional therapeutic benefits to patients with dyslipidemia. Under the terms of the agreement, AstraZeneca will pay $100 million upfront and pledge up to $1.92 billion in development and commercialization milestones. CSPC will also be entitled to tiered royalties if the molecule reaches the market. In return, AstraZeneca gains the right to advance YS2302018, an investigational oral small molecule disruptor of lipoprotein (a) (Lp(a)) that has been shown to effectively prevent its formulation, according to Monday’s press announcement. The pharma aims to develop the drug candidate, either alone or with its own experimental PCSK9 blocker AZD0780, for a variety of cardiovascular diseases. Sharon Barr, head of BioPharmaceuticals R&D at AstraZeneca, in a statement called CSPC’s Lp(a) blocker an “important addition” to the company’s cardiovascular pipeline, adding that YS2302018 can potentially “help patients to more effectively manage their dyslipidemia and related cardiometabolic diseases.” Lp(a) is a type of low-density lipoprotein (LDL) cholesterol characterized by an apolipoprotein(a) covalently bound to an apolipoprotein(B) molecule. High Lp(a) levels are associated with higher risks of heart attack and stroke, especially in patients with relevant medical histories, according to the Centers for Disease Control and Prevention (CDC). Currently, treatment levels for high Lp(a) are “limited,” as per the CDC, which lists apheresis as the only FDA-approved intervention. Exercise and a healthy lifestyle cannot directly lower Lp(a), but they are effective in controlling LDL-cholesterol concentrations, which in turn could help prevent cardiovascular diseases. With Monday’s CSPC deal, AstraZeneca joins Eli Lilly in the Lp(a) arena. In August 2023, the Indiana-based pharma released Phase I data for muvalaplin —which, like YS2302018, is an investigational oral Lp(a) inhibitor—demonstrating 63% to 65% maximum placebo-adjusted reductions in Lp(a). More than 90% of muvalaplin-treated participants reached Lp(a) levels lower than 50 mg/dL. Lilly has moved muvalaplin into Phase II development for cardiovascular diseases. Aside from muvalaplin, Lilly is also working on lepodisiran, an investigational siRNA therapeutic designed to silence the LPA gene, which encodes for Lp(a). According to the pharma’s pipeline webpage, lepodisiran is being developed for atherosclerotic cardiovascular disease. Also in the Lp(a) arena, Novartis and Ionis have partnered to advance the potentially first-in-class antisense therapy pelacarsen, which lowers circulating Lp(a) levels by suppressing the production of apolipoprotein(a) in the liver. Pelacarsen is currently in late-stage development for the secondary prevention of cardiovascular events in patients with high Lp(a).

While drugs are available that reduce levels of a lipoprotein (a), a protein associated with cardiovascular disease, no currently available therapies target this protein directly. Several companies are in various stages of clinical development with drugs that could tackle this protein, and AstraZeneca is paying $100 million to license a preclinical drug gives it a contender in the chase. AstraZeneca’s new cardiovascular asset comes from Hong Kong-based CSPC Pharmaceutical Group. Beyond the upfront payment, the pharmaceutical giant could pay out up to $1.92 billion if the drug achieves development and commercialization milestones, according to deal terms announced Monday. CSPC will also receive royalties from sales of a commercialized product. The CSPC drug, named YS2302018, is in development for dyslipidemia, which is abnormally high levels of cholesterol in the blood. One biological indicator of this condition is high levels of lipoprotein (a), or Lp(a), a type of protein that transports cholesterol through the blood. High Lp(a) levels increase the likelihood of cholesterol buildup in the walls of blood vessels and they are a known risk factor for cardiovascular disease, including coronary artery disease and stroke. presented by Sponsored Post The Promise of Value-Based Care and MedTech Innovation Monica Vajani, Executive Director for mHUB’s MedTech Accelerator, discusses how mHUB is helping innovators transition healthcare towards value-based care. By Monica Vajani - mHUB Lp(a) levels can already be reduced by therapies addressing PCSK9, a liver protein that regulates cholesterol. Studies of the approved PCSK9 inhibitors Repatha from Amgen, and Praluent from Regeneron Pharmaceuticals, showed reductions in Lp(a) levels. Novartis’s approved small interfering RNA (siRNA) therapy Leqvio takes a different approach by silencing the gene that produces PCSK9. That drug also reduces Lp(a). But these therapies do not address Lp(a) directly and they are all administered as injections. AstraZeneca describes CSPC’s YS2302018 as an oral Lp(a) disruptor. Compared to the available injectable therapies addressing PCSK9, the CSPC drug offers the convenience of once-daily oral dosing. That formulation gives AstraZeneca a way to catch up to and potentially compete with Eli Lilly in the treatment of dyslipidemia. Lilly’s muvalaplin is an oral small molecule disrupter of Lp(a) currently in Phase 2 testing. Lilly is also part of a group of companies developing siRNA therapies that reduce Lp(a) levels. The Indianapolis-based pharma giant’s lepodisiran earlier this year began a Phase 3 clinical trial in atherosclerotic cardiovascular disease. Amgen’s olpasiran is in Phase 3 testing in the same indication while Silence Therapeutics’ is preparing to enter pivotal testing with its Lp(a)-reducing drug candidate, zerlasiran. Pelacarsen, an Ionis Pharmaceuticals antisense oligonucleotide intended to reduce Lp(a) production, is in Phase 3 testing under a partnership with Novartis. AstraZeneca’s cardiovascular, renal, and metabolism drug lineup is anchored by the blockbuster products Farxiga (approved for type 2 diabetes, heart failure, and chronic kidney disease) and Brilinta (approved for coronary acute syndromes). The company says the CSPC drug has potential uses in a range of cardiovascular disease indications as a standalone treatment or in combination with other therapies. presented by Health Tech What’s Keeping Healthcare CIOs Up at Night: How to Improve Patient Satisfaction by Handling Calls More Efficiently Health systems have spent billions on portals while investments in modernizing the voice channel — the dominant preference of healthcare consumers — have taken a backseat. By Stephanie Baum One potential combination could pair the CSPC drug with AstraZeneca’s own PCSK9 inhibitor, AZD0780. In May, the pharma giant reported Phase 1 results showing once-daily oral doses of AZD0780 on top of statin therapy led to a statistically significant 52% reduction in levels of LDL cholesterol. The drug was well tolerated and no serious adverse events were reported. AstraZeneca is currently testing the pill in a Phase 2 clinical trial with a targeted enrollment of 428 participants. “Given the scale of unmet need, with cardiovascular disease being a leading cause of death globally, advancing novel therapies that can be used alone or in combination to effectively address known risk factors and advance patient care is particularly important and a key part of our strategy,” Sharon Barr, AstraZeneca executive vice president and head of biopharmaceuticals R&D, said in a prepared statement.