Novartis, Ionis' experimental heart drug misses key goal in closely watched trial

Sept 4 — Novartis said on Friday its experimental drug pelacarsen did not cut the risk of major heart attacks and ​strokes in patients with a genetic risk factor in a late-stage trial, marking a setback to the Swiss drugmaker's efforts to revive its drug pipeline.

The study results are among several tests for Novartis' late-stage drug pipeline ‌this year, as it navigates one of its steepest patent expiries and the loss of revenue from its blockbuster heart drug Entresto.

U.S.-listed shares of Novartis declined 5%, ⁠while partner Ionis stock Pharmaceuticals fell 12% in aftermarket ​trading.

"These are not the results we hoped for, but they ⁠provide important evidence that advances scientific understanding of the relationship between Lp(a) lowering and cardiovascular outcomes," said Novartis chief medical ‌officer Shreeram Aradhye.

Investors are focused on ‌pelacarsen, anti-inflammatory drug remibrutinib, and gene therapy del-desiran, as key drivers of the company's long-term growth as ⁠they could together generate more than $10 billion in peak annual sales, if ⁠approved. Earlier this week, remibrutinib succeeded in a late-stage study of patients with a form of multiple sclerosis and analysts expect it alone could bring in up to $9 billion in peak annual sales.

Pelacarsen is a subcutaneous injection given once a month that lowers lipoprotein (a) or Lp(a)– a type of genetically inherited cholesterol that has been linked to higher heart risk.

The trial was the first late-stage study to test whether the drug can prevent heart attacks and ‌strokes in patients with already well-controlled "bad cholesterol" that is not inherited. It ran for ​more than six years and tested over 8,000 patients with high levels of Lp (a).

Consistent with previous studies, pelacarsen lowered levels of the cholesterol-carrying particle lipoprotein(a) or Lp (a) in patients, the companies said.

Citi analyst Geoff Meacham said full trial data are needed to determine whether the miss reflects pelacarsen's mechanism of action, inadequate Lp(a) reduction, trial design, or doubts that lowering Lp(a) reduces heart disease risk.

There are currently no approved treatments specifically designed to lower Lp(a), which affects 20% of people worldwide.

"The first dedicated outcomes failure lowers confidence across the class and places greater pressure on later studies ​to demonstrate that deeper lowering of Lp(a) can produce a clinically meaningful reduction of major cardiovascular events", said Meacham.

Other experimental Lp(a)-lowering drugs in development include ‌Amgen's olpasiran and ‌Eli Lilly's lepodisiran, both ⁠of which are in late-stage development. Amgen shares also fell 5% in aftermarket trading.

Modern cholesterol drugs, such as high dose statins and weight-loss drugs like GLP-1s are already effective at keeping patients healthy that fewer heart strokes and emergencies occur during clinical studies, such as pelacarsen's study. This makes it much harder for new, experimental drugs to prove they can offer any extra ‌protection.

Ionis discovered and conducted the early ​development of pelacarsen. In 2019, Novartis exercised an option to license the ‌rights to develop and commercialize pelacarsen ⁠for cardiovascular therapy.

The companies ​said full trial data will be presented at an upcoming medical congress.

(Reporting by Christy Santhosh in Bengaluru and Bhanvi Satija in London; Editing ​by Shailesh Kuber)

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