Eplontersen Phase 3 Failure Shifts Ionis Pharmaceuticals Investment Focus

Pelacarsen, an experimental Lp(a)-lowering drug from Novartis AG and partner Ionis Pharmaceuticals, Inc., failed to reduce heart attacks, strokes and related cardiovascular events in the Phase III Lp(a)HORIZON trial, which enrolled more than 8,000 patients, Reuters reported on September 5, 2026. The drug did lower Lp(a) levels as expected, but that reduction did not translate into fewer real-world cardiac events. Novartis shares fell 5% and Ionis shares fell 12% in aftermarket trading. Novartis called the results a disappointment but said they still advance scientific understanding of the Lp(a) pathway. The failure removes a major potential growth driver for both companies and raises the burden of proof for other Lp(a) drugs, with Novartis now under greater pressure to replace revenue as Entresto and other products approach patent challenges. Ionis faces greater concentration risk because pelacarsen mattered more to the smaller company, though its broader RNA portfolio and newly approved Zanvastro for Alexander disease provide some diversification.

UnitedHealth has sold an interest in some of its Optum Health operations in Florida to private equity firm TPG, part of the health conglomerate's effort to recover from a collapse in profits last year. CFO Wayne DeVeydt told Bloomberg News that Optum Health margins will be around 2% this year, above prior expectations, and should rise to around 4% in 2027 and 6% the following year. Amgen fell more than 8%, its worst single-day decline since 2016, after Novartis announced a Phase 3 trial failure for the heart disease therapy pelacarsen, which it is developing with Ionis Pharmaceuticals; BMO Capital Markets downgraded Amgen to Market Perform from Market Outperform with a $450 price target. CooperCompanies dropped 13% after issuing fiscal 2026 guidance below consensus, with revenue of $4.229B-$4.252B versus the prior $4.285B-$4.321B and non-GAAP diluted EPS of $4.51-$4.55 versus $4.58-$4.66 previously, and said its board decided to keep CooperSurgical rather than sell it while raising its share buyback authorization to $3B from $2B. Novo Nordisk fell more than 1% premarket after Morgan Stanley downgraded the stock to Underweight from Equal-weight, citing the semaglutide patent cliff, and the S&P 500 Health Care Sector Index slipped more than 3.5% for the week.

Royalty Pharma plc disclosed that pelacarsen failed the Phase 3 Lp(a)HORIZON cardiovascular-outcomes trial run by Novartis AG, which enrolled 8,323 patients with elevated lipoprotein(a) and established cardiovascular disease. The drug lowered Lp(a) but did not meet the primary endpoint of reducing cardiovascular events versus placebo in the overall population, and complete results have not yet been presented. Royalty Pharma had provided Ionis Pharmaceuticals $500 million in January 2023, allocating $150 million to pelacarsen royalties and $350 million to Spinraza royalties, and it now expects to pay no pelacarsen milestone payments out of up to $625 million in potential regulatory and commercial milestones. The company holds 25% of Ionis's Spinraza royalties through 2027, rising to 45% in 2028 on Spinraza annual sales of up to $1.5 billion, with that interest reverting after aggregate payments reach $550 million, or 1.1 times the original funding. Management expects the structure to recover the entire investment and generate a modest positive return, and it maintained its 2030 target of at least $4.7 billion in company-defined Portfolio Receipts.