Zerlasiran—A Small-Interfering RNA Targeting Lipoprotein(a)): A Phase 2 Randomized Clinical Trial
Authors' conclusion
Zerlasiran was well-tolerated and reduced time-averaged lipoprotein(a) concentration by more than 80% during 36 weeks of treatment in patients with ASCVD.
Study context
- Population
- Patients with stable atherosclerotic cardiovascular disease (ASCVD) and serum lipoprotein(a) ≥125 nmol/L172 completed
- Participants
- 178 patients
- Comparison
- Zerlasiran vs placebo
- 450 mg every 24 weeksn = 45
- 300 mg every 16 weeksn = 42
- 300 mg every 24 weeksn = 44
- Primary endpoint
- Time-averaged percent change in lipoprotein(a) concentration from baseline
- Follow-up
- 36 weeks
Methodological detailsmulticentre, placebo-controlled, 26 sites in Europe and South Africa
- Multicentre
- Placebo-controlled
- 26 sites in Europe and South Africa
Primary result
As reported in the abstract
Time-averaged % change in lipoprotein(a) vs pooled placebo (least-squares mean) · week 36
Each group vs placeboLeast-squares mean difference, % (95% CI)
450 mg every 24 weeks
−85.6(−90.9% to −80.3%)
300 mg every 16 weeks
−82.8(−88.2% to −77.4%)
300 mg every 24 weeks
−81.3(−86.7% to −76.0%)
Further findings
Median, %
| Outcome | Placebo | 450 mg every 24 weeks | 300 mg every 16 weeks | 300 mg every 24 weeks | |
|---|---|---|---|---|---|
| Percent change in lipoprotein(a) · week 36 | Not reported in the abstract | −94.5 (IQR −97.3%–-84.2%) | −96.4 (IQR −97.7%–-92.3%) | −90.0 (IQR −93.7%–-81.3%) | Placebo: not reported in the abstract |
Safety
Injection site reactions (mild pain, first day after dosing)
- Mild pain at injection site, range across zerlasiran groups
- 2.3% to 7.1%
- Most common treatment-related adverse effects
Serious adverse events
- Serious adverse events
- 20 in 17 patients
- Serious adverse events considered related to study drug
- 0
Original publication
Zerlasiran—A Small-Interfering RNA Targeting Lipoprotein(a)): A Phase 2 Randomized Clinical Trial. JAMA. Published 17 December 2024. doi:10.
Summarised from the published abstract; every number is checked against it