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MDCO-216 Does Not Induce Adverse Immunostimulation, in Contrast to Its Predecessor ETC-216
Joannes A A Reijers1,2, D G Kallend3, K E Malone4,5
1Centre for Human Drug Research, Zernikedreef 8, 2333CL, Leiden, The Netherlands. jreijers@chdr.nl.
Purpose:
Aim of this study was to demonstrate that MDCO-216 (human recombinant Apolipoprotein A-I Milano) does not induce adverse immunostimulation, in contrast to its predecessor, ETC-216, which was thought to contain host cell proteins (HCPs) that elicited an inflammatory reaction.
Methods:
Data were taken from a clinical trial in which 24 healthy volunteers (HV) and 24 patients with proven stable coronary artery disease (sCAD) received a single intravenous dose of MDCO-216, ranging 5-40 mg/kg. Additionally, whole blood from 35 HV, 35 sCAD patients and 35 patients requiring acute coronary intervention (aCAD group) was stimulated ex vivo with MDCO-216 and ETC-216.
Results:
No inflammatory reaction was observed in HV and sCAD patients following MDCO-216 treatment, judging by body temperature, white cell counts, neutrophil counts, C-reactive protein, circulating cytokines (IL-6, TNF-α), and adverse events. In the ex vivo experiment, the geometric means (SD) of the ratio of MDCO-216 stimulated IL-6 over background levels were 0.8 (1.9), 0.7 (1.5), 1.0 (2.0) for respectively HV, sCAD, aCAD. The corresponding ETC-216 stimulated values were 15.8 (2.9), 9.5 (3.6), 3.8 (4.0). TNF-α results were comparable. Because many ETC-216 stimulated samples had cytokine concentrations >ULOQ, ratios were categorised and marginal homogeneity of the contingency table (MDCO-216 versus ETC-216) was assessed with the Stuart-Maxwell test. P-values were ≤0.0005 for all populations.
Conclusions:
MDCO-216 did not induce adverse immunostimulation in HV and sCAD patients, in contrast to ETC-216. Results from the ex vivo stimulation suggests the same holds true for aCAD patients.
Insights
MDCO-216, a novel ApoA-I Milano, showed no adverse immunostimulation in patients with coronary artery disease. This contrasts with ETC-216, indicating MDCO-216
Area of Science:
- Cardiovascular Medicine
- Immunology
- Pharmacology
Background:
- The predecessor drug, ETC-216, was associated with inflammatory reactions.
- This reaction was potentially due to host cell proteins (HCPs) in ETC-216.
- MDCO-216 is a human recombinant Apolipoprotein A-I Milano designed to avoid these issues.
Purpose of the Study:
- To evaluate if MDCO-216 induces adverse immunostimulation.
- To compare the immunostimulatory potential of MDCO-216 with ETC-216.
Main Methods:
- A clinical trial involving 24 healthy volunteers and 24 stable coronary artery disease (sCAD) patients receiving single intravenous doses of MDCO-216 (5-40 mg/kg).
- Ex vivo whole blood stimulation assays using MDCO-216 and ETC-216 in healthy volunteers (HV), sCAD patients, and acute coronary intervention (aCAD) patients.
Main Results:
- No inflammatory markers (temperature, white blood cell counts, CRP, IL-6, TNF-α) were elevated in patients treated with MDCO-216.
- Ex vivo, MDCO-216 showed minimal IL-6 and TNF-α induction compared to background levels across all groups.
- ETC-216 induced significant elevations in IL-6 and TNF-α (p≤0.0005) compared to MDCO-216.
Conclusions:
- MDCO-216 does not induce adverse immunostimulation in healthy volunteers and sCAD patients.
- Ex vivo data suggest MDCO-216 is also safe for aCAD patients regarding immunostimulation.
- MDCO-216 represents a safer alternative to ETC-216, lacking the immunostimulatory effects.
