Trial results for a Phase 2 study (NCT04992065) investigating the efficacy of NNC0385-0434 tablets and comparing them to evolocumab 140 mg (Repatha®) for lowering blood cholesterol in people with heart disease or high risk of heart disease were posted on ClinicalTrials.gov on 2025-06-08. The study showed that evolocumab 140 mg achieved a mean low-density lipoprotein (LDL)-cholesterol reduction of -59% (Standard Deviation: 22).
Background
The study aimed to evaluate how well a new medicine, NNC0385-0434, works to lower blood cholesterol levels. Evolocumab (Repatha®) was included as an active comparator, being a medicine that doctors can already prescribe for cholesterol management in patients with conditions such as Atherosclerotic Cardiovascular Disease.
Trial design
The study (NCT04992065) was a Phase 2, randomized trial that enrolled 267 participants. The trial investigated treatments for individuals with Atherosclerotic Cardiovascular Disease or a high risk of heart disease. Participants were randomized to receive one of several interventions: NNC0385-0434 at doses of 15 mg, 40 mg, or 100 mg as a tablet, a placebo tablet, or evolocumab 140 mg/ml as an injection. The study primarily focused on the percentage change in low-density lipoprotein (LDL)-cholesterol and total cholesterol.
Key results
The trial results demonstrated significant changes in cholesterol levels across the treatment groups. For the outcome of "Percentage Change in Low-density Lipoprotein (LDL)-Cholesterol":
- Participants receiving NNC0385-0434 15 mg achieved a mean reduction of -27% (Standard Deviation: 19).
- Participants receiving NNC0385-0434 40 mg achieved a mean reduction of -41% (Standard Deviation: 37).
- Participants receiving NNC0385-0434 100 mg achieved a mean reduction of -55% (Standard Deviation: 20).
- Participants receiving Placebo showed a mean increase of 6% (Standard Deviation: 41).
- Participants receiving Evolocumab 140 mg achieved a mean reduction of -59% (Standard Deviation: 22).
Analyses of covariance (ANCOVA) for LDL-C percentage change at week 12 from baseline showed:
- The treatment difference for NNC0385-0434 15 mg compared to placebo was -31.95 (95.0% CI: -43.02 to -20.87), with a p-value of 0.0001.
- The treatment difference for NNC0385-0434 40 mg compared to placebo was -44.91 (95.0% CI: -56.04 to -33.79), with a p-value of 0.0001.
- The treatment difference for NNC0385-0434 100 mg compared to placebo was -61.83 (95.0% CI: -72.94 to -50.72), with a p-value of 0.0001.
- The treatment difference for Evolocumab 140 mg compared to NNC0385-0434 100 mg was 3.43 (95.0% CI: -7.81 to 14.68).
For "Percentage Change in Total Cholesterol":
- NNC0385-0434 15 mg: mean reduction of -14% (Standard Deviation: 13).
- NNC0385-0434 40 mg: mean reduction of -25% (Standard Deviation: 27).
- NNC0385-0434 100 mg: mean reduction of -33% (Standard Deviation: 11).
- Placebo: mean increase of 4% (Standard Deviation: 23).
- Evolocumab 140 mg: mean reduction of -38% (Standard Deviation: 14).
For "Percentage Change in High Density Lipoprotein (HDL)-Cholesterol":
- NNC0385-0434 15 mg: mean increase of 4% (Standard Deviation: 13).
- NNC0385-0434 40 mg: mean increase of 5% (Standard Deviation: 16).
What this means
The results from this Phase 2 trial indicate that evolocumab 140 mg significantly reduced LDL-C levels in patients with Atherosclerotic Cardiovascular Disease, demonstrating a strong lipid-lowering effect. The data also suggest that the investigational drug NNC0385-0434 100 mg achieved a comparable LDL-C reduction to evolocumab 140 mg, with a treatment difference of 3.43 (95.0% CI: -7.81 to 14.68) between the two. These findings provide important insights into the potential of NNC0385-0434 as an oral therapeutic option for cholesterol management, while reaffirming the efficacy of evolocumab.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT04992065, titled "A Research Study Looking at How NNC0385-0434 Tablets Work to Lower Blood Cholesterol in People With Heart Disease or a High Risk of Heart Disease," were posted on 2025-06-08 on clinicaltrials.gov.