Key Takeaways
- Shares of Novartis declined more than 3% Monday following negative results from the pelacarsen cardiovascular outcomes trial
- The Lp(a)HORIZON study enrolled over 8,000 participants but failed to demonstrate reduction in major cardiovascular events
- While pelacarsen successfully reduced lipoprotein(a) levels, this biomarker improvement didn’t result in clinical benefit
- The disappointing outcome casts doubt on similar Lp(a)-lowering therapies being developed by Amgen and Eli Lilly
- Novartis shares have gained 14% year-to-date following Monday’s decline
Shares of Novartis tumbled over 3% during European trading hours Monday following the announcement that pelacarsen, its investigational cardiovascular therapy, missed the primary endpoint in a pivotal late-stage clinical study. The decline trimmed the pharmaceutical company’s year-to-date advance to approximately 14%.
The clinical study at the center of the disappointment is Lp(a)HORIZON, a comprehensive trial that recruited over 8,000 individuals with high levels of lipoprotein(a), a cholesterol-containing particle associated with increased cardiovascular risk.
While pelacarsen demonstrated efficacy in reducing Lp(a) concentrations, this biochemical change failed to produce meaningful reductions in cardiovascular events such as myocardial infarction, stroke, or cardiovascular mortality.
This disconnect between biomarker reduction and clinical outcomes represents a significant challenge that few drugs can overcome.
Shreeram Aradhye, Chief Medical Officer at Novartis, expressed disappointment with the findings, stating the outcome was “not what we hoped for.” However, he emphasized that the data still contributes valuable insights into understanding the complex relationship between Lp(a) reduction and cardiovascular protection.
Implications for Competing Therapies
The setback extends beyond Novartis alone. Both Amgen and Eli Lilly have active programs developing Lp(a)-targeting medications, albeit using alternative mechanisms of action. The pelacarsen results prompt important questions about whether simply lowering Lp(a) concentrations is sufficient to deliver cardiovascular protection.
To date, no therapy specifically designed to lower lipoprotein(a) has received regulatory approval, despite elevated Lp(a) levels affecting approximately 20% of the global population.
Novartis obtained rights to pelacarsen through a licensing agreement with Ionis Pharmaceuticals. The compound is classified as an antisense oligonucleotide, which works by inhibiting Lp(a) production at the genetic level.
Additional Pipeline Challenges
Jefferies analysts observed that the increasing effectiveness of current cardiovascular medications, coupled with the emergence of GLP-1 receptor agonists for obesity management, has elevated expectations for new cardiac therapies to demonstrate meaningful clinical benefits in outcome studies.
This trial setback arrives just days after Novartis suspended eight clinical studies of an investigational cell-based therapy for autoimmune and neurological conditions following three patient fatalities.
According to Jefferies, encouraging data from a recent multiple sclerosis study should provide some reassurance to the investment community.
Nevertheless, the firm highlighted that Novartis faces mounting pressure to generate successful results from therapies obtained through its $12 billion acquisition of Avidity Biosciences to validate that substantial investment.
Complete findings from the Lp(a)HORIZON study are scheduled to be shared at an upcoming medical conference.
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