Zerlasiran (formerly SLN360), a gene-silencing therapy, has shown sustained reductions in lipoprotein(a) [Lp(a)] levels through 60 weeks, according to data from the ALPACAR-360 trial presented at the American Heart Association (AHA) Scientific Sessions 2024. This offers a potential treatment for individuals with elevated Lp(a), a genetic risk factor affecting approximately 20% of the global population and a significant contributor to cardiovascular disease.
ALPACAR-360 Trial Results
The Phase 2 trial, initiated in 2023, involved 178 patients with baseline Lp(a) levels exceeding 125 nmol/L and a high cardiovascular risk profile. Participants were randomized to receive one of three dosing regimens of zerlasiran or a placebo. At 36 weeks, zerlasiran demonstrated a least-squares mean time-averaged Lp(a) reduction ranging from -81.3% to -85.6%.
Stephen J. Nicholls, MD, PhD, Victorian Heart Institute, Monash University, commented on the efficacy and durability of zerlasiran, stating, "Our ability to show more and more durability, more Lp(a) lowering 6-, 12-months after injections, has implications for potentially less frequent dosing."
Dosage and Tolerability
The study evaluated zerlasiran at 450 mg every 24 weeks (-85.6%; 95% CI, -90.9% to -80.3%), 300 mg every 16 weeks (-82.8%; 95% CI, -88.2% to -77.4%), and 300 mg every 24 weeks (-81.3%; 95% CI, -86.7 to -76.0). These reductions were consistently maintained through the 60-week mark. Zerlasiran was generally well-tolerated, with the most common treatment-related adverse events being mild injection site reactions. Twenty serious adverse events were reported in 17 patients, but none were attributed to the study drug.
Future Directions
Nicholls highlighted the competitive profile of zerlasiran, suggesting its potential as a long-term therapy with infrequent dosing. The drug is poised to advance into Phase 3 trials as a promising treatment option for patients with elevated Lp(a). Nicholls also noted the importance of monitoring and managing adverse events, emphasizing the need for open communication with patients regarding potential side effects to ensure long-term treatment adherence.
