Visible Alpha consensus shows Novartis pipeline reset after trial failures

Swiss pharma giant Novartis AG (SIX: NOVN) has suffered two late-stage clinical setbacks in September, raising the stakes for its pipeline as it seeks to build growth beyond the current generation of medicines.

Pelacarsen, which Novartis is developing with Ionis Pharmaceuticals, Inc. (NASDAQ: IONS) for patients with elevated lipoprotein(a), or Lp(a), and established cardiovascular disease, failed to meet the primary endpoint of the Phase III Lp(a)HORIZON trial. Although the drug substantially lowered Lp(a) levels, this did not translate into a reduction in cardiovascular events, raising questions about whether lowering the inherited cardiovascular risk factor is sufficient to prevent heart attacks, strokes and other major events.

Just days later, del-desiran, the lead asset acquired through Novartis’ $12 billion purchase of Avidity Biosciences Inc., also missed its primary endpoint in the Phase III HARBOR study in myotonic dystrophy type 1.

Visible Alpha consensus reflects the deterioration in expectations. Analysts now assign del-desiran a 44% probability of success, while the probability for pelacarsen has fallen to 37.5%, from 58.75% before the Phase III readout. Risk-adjusted sales expectations for both drugs have also been cut, reducing the contribution investors had been assigning to the pipeline.

Pelacarsen and del-desiran were among three major late-stage programs expected to contribute to the next phase of growth, alongside remibrutinib, which delivered positive Phase III results in multiple sclerosis earlier in September.

Pelacarsen’s failure also has implications beyond Novartis. The drug lowered Lp(a), but the absence of a cardiovascular benefit leaves an important question for the broader class: whether reducing Lp(a) is sufficient to prevent cardiovascular events.

That makes the outcome a significant read-through for Amgen Inc. (NASDAQ: AMGN) and its olpasiran program, another Lp(a)-lowering therapy in Phase III development. Visible Alpha consensus shows risk-adjusted sales have also moved lower for olpasiran following the pelacarsen result.

This article was published by Visible Alpha, part of S&P Global Market Intelligence and not by S&P Global Ratings, which is a separately managed division of S&P Global.