Shares of Novartis, Amgen and Ionis tumbled on Tuesday morning
Novartis' disclosure that a Lp(a)-lowering drug failed to reduce the risk of cardiovascular events like heart attacks and stroke in a Phase 3 study rippled across biopharma stocks on Tuesday.
A major clinical-trial failure last week is rippling across biopharma stocks on Tuesday morning, showing yet again how risky it is to invest in drug development.
Novartis announced late Friday that its Phase 3 study evaluating pelacarsen showed the drug designed to lower lipoprotein (a), or Lp(a), didn't reduce the risk of serious cardiovascular events, including heart attacks and stroke. The Swiss drugmaker is expected to share data from the trial at a later date.
Along with several other drugmakers, Novartis has bet that lowering Lp(a) will cut the risk of these sometimes fatal events. Pelacarsen did lower Lp(a), a cholesterol-carrying particle that raises the risk of those events, but it didn't lessen those risks.
The failure raises questions about whether lowering Lp(a) is a viable way to lower the risk of cardiovascular events, though analysts and industry insiders are still debating what's possible. "Historically, we've been mixed on Lp(a) as a therapeutic target," Jefferies analyst Akash Tewari told investors over the weekend.
"A different outcome remains plausible with an asset that delivers deeper, more consistent and more durable Lp(a) lowering," BMO Capital Markets analyst David Lebowitz wrote in a note on Monday.
Novartis licensed pelacarsen from biotech Ionis Pharmaceuticals for $60 million upfront in 2023. Switzerland-listed shares of Novartis (CH:NOVN) tumbled 10.2% in trading on Tuesday, while Ionis's stock $(IONS)$ fell about 7.2% at market open on Tuesday.
In a note on Sunday, Leerink Partners analyst David Risinger described the trial's failure "as negative for biopharma-sector perception." By Monday morning, several biopharma stocks, including Amgen $(AMGN)$ and Sarepta Therapeutics (SRPT), were trading lower in reaction to the failed trial and broader concerns about lowering Lp(a) as a therapeutic tool for these patients.
About one in five people in the U.S. have high Lp(a), according to the Family Heart Foundation. High Lp(a) is hereditary, and interventions like diet or taking a statin rarely help lower Lp(a) levels in these patients. That's why drugmakers are working on new therapies to see whether a different mechanism of action will improve outcomes for these patients.
Pelacarsen is an antisense oligonucleotide, while Eli Lilly and Amgen are each working on siRNA therapies that aim to lower Lp(a). A small interfering RNA drug, or siRNA, "turns off" specific genes.
Amgen, which has a Phase 3 trial under way for its own Lp(a) drug candidate, saw its shares fall 8.2%. Its stock decline dragged down the Dow on Tuesday morning. Lilly's shares (LLY) were down about 2.7% - it has two Lp(a) drugs in Phase 3 trials.
The impact of the Novartis failure extended to biotechs working on adjacent therapies.
NewAmsterdam $(NAMS)$ is developing an LDL-C-lowering therapy, though analysts noted that lowering Lp(a) in this study is an add-on benefit rather than the main focus. Its shares were down 6.7%.
Separately, Novartis on Monday disclosed another Phase 3 failure of an experimental treatment for people with myotonic dystrophy type 1, which came from its $12 billion acquisition of Avidity Biosciences last year. Sarepta Therapeutics (SRPT), which is working on siRNA therapies to treat people with two types of muscular dystrophy, saw its stock tumble 11.5%.
-Jaimy Lee