Novartis Cholesterol Drug Failure Clouds Lp(a) Treatment Race

Shares in Novartis (NVS) fell more than three per cent after its experimental cholesterol-lowering drug pelacarsen failed in a closely watched late-stage study, erasing what analysts had expected to be a blockbuster revenue stream and heaping pressure on upcoming data from a muscle-wasting therapy the Swiss drugmaker acquired through its $12bn purchase of Avidity.

The failure of pelacarsen — which had been forecast to generate peak annual sales of between $3bn and $6bn — deals a significant blow to broader industry efforts to treat lipoprotein(a), or Lp(a), an inherited cardiovascular risk factor for which no approved therapy yet exists. Novartis announced late on Friday that the drug had not reduced the risk of heart attack and stroke in a large trial of patients with elevated Lp(a) levels.

The setback raises the burden of proof for rival programs from Amgen (AMGN) and Eli Lilly (LLY), which are running late-stage trials of their own experimental Lp(a)-lowering medicines, olpasiran and lepodisiran respectively. Both trials are structured similarly to pelacarsen's — dependent on confirmed cardiovascular events and without a fixed end date — though some analysts argued the rivals could yet succeed where Novartis failed. Amgen and Lilly's drugs have demonstrated stronger Lp(a) reductions in earlier-stage studies, and their trials are enrolling patients with particularly elevated levels of the protein, a distinction analysts suggested could prove consequential.

Barclays analysts said Novartis' second Lp(a)-targeting drug, DII235, now appears "unlikely to provide any meaningful benefit," further narrowing the company's options in the space.

Investor attention will now shift to fourth-quarter results from del-desiran, an RNA therapy for a rare muscle disease that Novartis acquired alongside Avidity. Barclays said success in that trial "is needed to justify" the acquisition price. Data from a study of remibrutinib, Novartis's anti-inflammatory drug, in patients with the skin condition hidradenitis suppurativa is also expected before year-end. The drug recorded a win in multiple sclerosis last week, which Jefferies analysts said should make the pelacarsen disappointment "more palatable" for investors.

Elsewhere in the Lp(a) field, Netherlands-based NewAmsterdam Pharma (NAMS) — whose drug obicetrapib targets standard LDL cholesterol rather than Lp(a) — is seen as less directly exposed to the trial failure. Biotechs CRISPR Therapeutics (CRSP) and Silence Therapeutics are also developing Lp(a) treatments; CRISPR's approach uses gene editing rather than temporarily blocking the protein. For Silence, which is seeking a partner to fund larger trials, William Blair analysts cautioned that the setback could complicate dealmaking until the full pelacarsen data is better understood. Novartis has said it plans to present complete results at a medical conference later this year.