Phase 1 study: single dose of Kylo-11 sharply lowers Lp(a) for up to 48 weeks

A first-in-human study published in The Lancet found that a single dose of the experimental RNA drug Kylo-11 was well tolerated and, at doses of 225 mg or higher, produced durable reductions in lipoprotein(a), or Lp(a), for up to 48 weeks.

The early result matters because Lp(a) is a common inherited cardiovascular risk factor that has long lacked a targeted treatment. Roughly 1 in 5 people worldwide are estimated to have elevated Lp(a), a cholesterol-like particle linked to atherosclerotic cardiovascular disease and calcific aortic valve disease. As of mid-2026, no Lp(a)-specific drug had won regulatory approval.

The trial, registered as NCT06363851 on ClinicalTrials.gov, was a randomized, double-blind, placebo-controlled phase 1 study in healthy volunteers designed to test safety, tolerability and effects on the biomarker. The single-ascending-dose study enrolled about 60 participants across planned dose groups of 9 mg, 30 mg, 75 mg, 225 mg, 450 mg and 600 mg, plus an additional 225 mg cohort for people with higher baseline Lp(a).

While The Lancet summary reported the topline finding, more detailed numbers come from sponsor-presented data previously shown at the American Heart Association Scientific Sessions in 2025 and from company materials. In those presentations, Hygieia Pharmaceuticals said median Lp(a) reductions at 24 weeks ranged from about 83.5% to 98.4% across cohorts. The company also reported durable effects deep into follow-up, including a median 77.6% reduction at week 48 in the 30 mg cohort, 88.8% at week 44 in the 75 mg cohort and 96.7% at week 40 in the 225 mg cohort. In a separate 225 mg cohort enrolling participants with baseline Lp(a) above 200 nmol/L, the reported median reduction was 98.4% at week 28. Hygieia has also said that serum Lp(a) stayed below 75 nmol/L in all participants receiving 30 mg or more starting four weeks after dosing during follow-up.

On safety, Hygieia said in its interim summary that Kylo-11 was safe and well tolerated across all study groups. Most treatment-emergent adverse events were grade 1 or 2 and judged unrelated to the drug, according to the company. It reported no serious treatment-emergent adverse events, no discontinuations and no injection-site reactions in the interim readout. In a company press release tied to the AHA presentation, principal investigator Professor Xiaolan Yong said, “Lp(a) is an independent risk factor for cardiovascular events, but we still don’t have an effective therapy to reduce Lp(a) level in clinical practice. The emergence of Kylo-11, an siRNA medicine specifically designed to lowering serum Lp(a) in human, is highly promising.”

Kylo-11 is part of a broader wave of RNA-based medicines aimed at Lp(a), including pelacarsen and olpasiran, that are trying to answer one of preventive cardiology’s biggest open questions. Hygieia describes Kylo-11 as an LPA-targeting small interfering RNA with the potential for once-yearly dosing, though that remains a company claim at this stage. A phase 2 randomized, double-blind, placebo-controlled study in China and the United States, registered as NCT07327840, is listed with an estimated enrollment of about 204 participants. The registry shows a start date of Oct. 29, 2025, with primary completion expected in February 2027.

Even so, the key limitation is unchanged: This was a small phase 1 study in healthy volunteers measuring a blood biomarker, not a trial showing fewer heart attacks, strokes or other cardiovascular events. For Kylo-11 — and for the Lp(a) field more broadly — the central question is not whether the drug can sharply lower Lp(a), but whether doing so will improve patients’ outcomes.