Pelacarsen

Ionis Pharmaceuticals' shares rose 5% after FDA approved its RNA-targeted therapy, Tryngolza, for familial chylomicronemia syndrome (FCS), marking the first treatment for FCS in the U.S. The approval is supported by phase III BALANCE study results showing significant triglyceride-lowering and reduced acute pancreatitis attacks. Tryngolza is Ionis' first wholly-owned drug and independent commercial launch, expected by year-end. The company is also evaluating Tryngolza for severe hypertriglyceridemia and has collaborations with major drugmakers for various treatments.

Eli Lilly's muvalaplin, an oral cholesterol-lowering drug, significantly reduced Lp(a) levels in a 12-week phase II study, meeting primary and secondary endpoints. Muvalaplin disrupts apolipoprotein(a) and apolipoprotein(b) interaction, potentially reducing cardiovascular risk. Lilly's stock has risen 24.7% this year.

Zerlasiran, an siRNA, reduced time-averaged Lp(a) concentrations by over 80% in a 36-week trial, marking the first time such reduction has been reported for an siRNA therapy. The study suggests that each successive dose of zerlasiran extends the duration of Lp(a) reduction, informing future phase 3 trials and potentially optimal dosing strategies for other siRNA therapies.

Two new drugs, an siRNA and an oral agent, reduced Lp(a) by 80% in phase II studies. Zerlasiran, the siRNA, lowered Lp(a) by 85% over 36 weeks, while muvalaplin, the oral agent, reduced Lp(a) by 70% with a traditional assay and over 85% with an intact assay. Both therapies offer potential for treating cardiovascular disease, with muvalaplin providing an oral alternative to injectables.

Muvalaplin, an oral drug, significantly reduced lipoprotein(a) (Lp[a]) by 70% in a traditional blood test and 85.5% in a new test, according to a phase 2 study presented at the 2024 AHA Scientific Sessions. The drug, developed by Eli Lilly, targets Lp(a), a genetically driven variant of LDL cholesterol linked to cardiovascular disease, with no current treatments. Muvalaplin disrupts the bonding of apo(a) to apoB, preventing Lp(a) formation, and also reduced oxidized phospholipids. The study involved doses of 10 mg, 60 mg, and 240 mg over 12 weeks, with 97% of participants achieving Lp(a) levels below 125 nmol/L. Phase 3 trials and cardiovascular outcomes trials are next steps before market potential.

Ionis Pharmaceuticals (IONS) reported a narrower-than-expected Q3 2024 loss of 95 cents per share, with total revenues of $134 million, beating estimates. The company's shares have declined 22.9% YTD. Ionis receives royalties from Biogen for Spinraza and co-markets Qalsody with Biogen. Wainua, co-marketed with AstraZeneca, was approved in the U.S. and the UK, generating $30 million in milestone payments. Commercial revenues were $76 million, missing estimates. Ionis maintained its 2024 financial guidance, expecting total revenues over $575 million and an adjusted operating loss of less than $475 million.

AstraZeneca entered an exclusive licensing deal with CSPC Pharmaceutical Group to develop a preclinical lipid-lowering drug candidate, YS2302018, aiming to treat dyslipidemia and related cardiometabolic diseases. The deal includes $100 million upfront and up to $1.92 billion in milestones, with CSPC eligible for royalties. YS2302018 is an oral small molecule disruptor of Lp(a), a type of LDL cholesterol linked to higher heart attack and stroke risks. AstraZeneca joins Eli Lilly and others in the Lp(a) drug development arena.