Single Shot of Kylo-11 Slashes Lp(a) by Up to 97% for Nearly a Year
A phase 1 trial of Kylo-11, a novel siRNA, achieved near-complete Lp(a) reduction lasting 48 weeks from one subcutaneous injection.
Summary
Elevated lipoprotein(a) — a cholesterol-like particle strongly linked to heart attack and stroke — has been nearly impossible to treat until recently. Kylo-11 is a new type of long-acting small interfering RNA (siRNA) designed to silence the gene that makes Lp(a). In this phase 1 trial, 57 adults with high Lp(a) received a single subcutaneous injection at one of seven doses. The drug was well tolerated with no serious drug-related adverse events. At the highest doses (225 mg and above), Lp(a) was reduced by 96–97% and this effect persisted for the full 48-week follow-up. Even the lowest dose tested (9 mg) cut Lp(a) by a median of 53%. These results suggest a single annual injection could potentially manage elevated Lp(a) — a cardiovascular risk factor affecting roughly one in five people worldwide.
Detailed Summary
Lipoprotein(a) — or Lp(a) — is a genetically determined lipid particle that dramatically raises the risk of atherosclerosis, heart attack, aortic stenosis, and stroke. Unlike LDL cholesterol, Lp(a) is largely resistant to statins and lifestyle changes, leaving hundreds of millions of high-risk people without an effective treatment option. Kylo-11 represents a potential breakthrough: a non-canonical small interfering RNA (siRNA) engineered for unusually long duration of action, designed to suppress hepatic production of Lp(a) with a single dose.
This randomised, double-blind, placebo-controlled phase 1 trial enrolled 71 adults in China aged 18–55 with elevated Lp(a). Participants were assigned across seven dose cohorts (9 to 600 mg) or placebo in an 8:2 ratio and received a single subcutaneous injection. Follow-up extended to 337 days for active recipients, with pharmacodynamic measurements tracked through 48 weeks.
Safety results were reassuring. While 53% of participants experienced some adverse event, the vast majority were mild (grade 1–2) and deemed unrelated to the drug. There were no injection-site reactions, no serious drug-related adverse events, and no deaths. Two grade 3 events in the 225 mg cohort were also adjudicated as unrelated.
The efficacy results were striking. At the 9 mg dose, median Lp(a) fell by 53% at 48 weeks. At 600 mg, reduction reached 97%. In cohort 7 — patients with very high baseline Lp(a) above 200 nmol/L given 225 mg — the median absolute reduction was 208 nmol/L, a 96% decrease. These reductions were durable across the entire follow-up period, suggesting Kylo-11's novel chemistry enables genuinely long-acting gene silencing.
Caveats include the early-phase design, a young and otherwise healthy study population (median age 27.5 years), single-site conduct in China, and industry funding. Full data are needed to confirm findings in older, higher-risk populations. Nonetheless, Kylo-11 joins a wave of RNA-targeted Lp(a) therapies that may soon offer once-yearly cardiovascular risk reduction.
Key Findings
- Single subcutaneous injection of Kylo-11 at 600 mg reduced Lp(a) by a median of 97% sustained through 48 weeks.
- Even the lowest dose tested (9 mg) cut Lp(a) by a median of 53% at 48 weeks from a single shot.
- Patients with very high baseline Lp(a) (>200 nmol/L) receiving 225 mg saw a median absolute drop of 208 nmol/L (-96%).
- No serious adverse events, no drug-related adverse events, no injection-site reactions, and no deaths were reported.
- Reductions were durable across the full 48-week follow-up, consistent with the drug's design as a very long-acting siRNA.
Methodology
Randomised, double-blind, placebo-controlled phase 1 trial with 71 participants across 7 dose cohorts (9–600 mg) conducted at a single site in China. Participants were followed for up to 337 days; the primary endpoint was adverse event incidence within 24 weeks. The trial is registered on ClinicalTrials.gov (NCT06363851) and is complete.
Study Limitations
Summary is based on the abstract only, as full-text is not open access. The trial enrolled a young, otherwise healthy cohort (median age 27.5 years) at a single site in China, limiting generalisability to older, higher-risk Western populations. Industry funding (Kylonova Biopharma) and multiple authors with financial conflicts of interest warrant independent replication.
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