Pelacarsen significantly lowered lipoprotein(a) in Novartis’ Phase 3 HORIZON trial but did not significantly reduce major cardiovascular events. Citi says the result could prompt CRISPR to favor CTX321 over CTX320 and sees under 5% immediate downside for Ionis shares.
Citi says HORIZON makes it more likely CRISPR will prioritize CTX321 over CTX320, but CRISPR has not announced such a change. CTX321 uses an updated guide RNA that showed about twice CTX320’s potency in preclinical testing; CTX320 has reduced Lp(a) by as much as 73% during dose escalation. Those results do not establish cardiovascular benefit in people, and CTX321 remains earlier in development. CRISPR expects to update the program in 2026.
Ionis discovered pelacarsen and licensed it to Novartis in 2019 for worldwide development and commercialization. Citi cited modest investor expectations in estimating limited immediate downside and, after speaking with Ionis management, said it did not expect the result to affect fiscal 2026 guidance. The trial failure nevertheless removes momentum from the partnered program and weakens a potential validation of Ionis’ antisense technology in Lp(a)-related cardiovascular disease.
