Assessing the clinical development of zerlasiran, a small-interfering RNA for elevated lipoprotein(a)

The GalNAc-conjugated siRNA zerlasiran reduces Lp(a) by targeting hepatic apo(a) synthesis and subsequent assembly of Lp(a), with comparable efficacy to other Lp(a)-lowering therapies in phase II development. Its long half-life, infrequent dosing, and potentially lower cost, together with its favorable safety and tolerability profile, make zerlasiran a promising candidate. However, long-term studies are needed to assess its impact on major adverse cardiovascular events and safety in diverse patient populations, and across different clinical settings. The phase III cardiovascular outcome study has not commenced.