First drug to treat Alexander disease approved by the FDA after three decades of research at UW–Madison

Ionis Pharmaceuticals (IONS) shares have fallen over 40% this year, despite analysts maintaining an average price target of $83.82. The company has six approved therapies, primarily for rare diseases, and is developing eight more in late-stage trials. Ionis reported a 40.7% revenue decline and a net loss in Q2, but analysts highlight its antisense oligonucleotide technology and potential for future growth.

Ionis Pharmaceuticals is focusing on growing TRYNGOLZA, a treatment for severe hypertriglyceridemia, while facing setbacks in its cardiovascular pipeline. The company is expanding TRYNGOLZA's market through disease awareness and physician education. Ionis is also advancing ION775, a follow-on candidate for sHTG, with phase II trials underway. However, the CARDIO-TTRansform study of eplontersen did not meet its primary endpoint, and the pelacarsen trial in Lp(a) cardiomyopathy was disappointing.

The FDA approved Zanvastro, the first drug to treat Alexander disease, a rare neurological disorder. Developed by Ionis Pharmaceuticals, it targets the GFAP protein. Clinical trials showed motor function stabilization and improvement. The drug will be available in the U.S. soon, with global distribution via Recordati.

Novartis and Ionis Pharmaceuticals' pelacarsen failed to reduce cardiovascular events in a Phase 3 trial, despite lowering lipoprotein(a) levels. This setback removes a potential revenue stream for Ionis, increasing pressure on its other late-stage RNA medicines. Analysts project $2.3B revenue and $222.2M earnings for Ionis by 2029, but the outcome raises execution risks and may extend the company's loss-making period.

Novartis (NVS) and Ionis (IONS) reported that their experimental cholesterol drug, pelacarsen, failed to reduce heart attacks and strokes in a late-stage trial, despite lowering Lp(a) levels. Shares of both companies fell in aftermarket trading. Novartis and Ionis acknowledged the setback but highlighted other pipeline opportunities. The failure removes a potential growth driver for both companies, with Novartis facing greater pressure to replace revenue as older drugs face patent challenges.

Novartis' pelacarsen failed to meet its primary endpoint in a late-stage study, impacting the cardiovascular drug market. Analysts expected peak sales of $4B-$5B. Eli Lilly's (LLY) stock declined only 3%, as its lepodisiran drug uses a different approach and Lilly has strong diabetes/obesity markets. Novartis (NVS) and Amgen (AMGN) are also developing Lp(a)-lowering drugs.