Case Report: Arterial Wall Inflammation in Atherosclerotic Cardiovascular Disease is Reduced by Olamkicept (sgp130Fc)

Dominik M Schulte; Georg H Waetzig; Harald Schuett; Marlies Marx; Berenice Schulte; Christoph Garbers; Juliane Lokau; Ann-Kathrin Vlacil; Juliane Schulz; Anna K Seoudy; Bernhard Schieffer; Philip Rosenstiel; Marcus Seeger; Matthias Laudes; Stefan Rose-John; Ulf Lützen; Karsten Grote; Stefan Schreiber

doi:10.3389/fphar.2022.758233

Case Report: Arterial Wall Inflammation in Atherosclerotic Cardiovascular Disease is Reduced by Olamkicept (sgp130Fc)

Front Pharmacol. 2022 Jun 9:13:758233. doi: 10.3389/fphar.2022.758233. eCollection 2022.

Authors

Dominik M Schulte^{1

2}, Georg H Waetzig^{3

4}, Harald Schuett⁵, Marlies Marx⁶, Berenice Schulte¹, Christoph Garbers⁷, Juliane Lokau⁷, Ann-Kathrin Vlacil⁵, Juliane Schulz¹, Anna K Seoudy¹, Bernhard Schieffer⁵, Philip Rosenstiel³, Marcus Seeger¹, Matthias Laudes^{1

2}, Stefan Rose-John⁸, Ulf Lützen⁶, Karsten Grote⁵, Stefan Schreiber^{1

3}

Affiliations

¹ Department of Internal Medicine I, University Medical Center Schleswig-Holstein (UKSH), Kiel, Germany.
² Institute of Diabetes and Clinical Metabolic Research, Kiel University and UKSH, Kiel, Germany.
³ Institute of Clinical Molecular Biology, Kiel University and UKSH, Kiel, Germany.
⁴ CONARIS Research Institute AG, Kiel, Germany.
⁵ Department of Cardiology and Angiology, Philipps-University, Marburg, Germany.
⁶ Department of Nuclear Medicine, Molecular Imaging Diagnostics and Therapy, UKSH, Kiel, Germany.
⁷ Department of Pathology, Otto-von-Guericke-University, Magdeburg, Germany.
⁸ Biochemical Institute, Kiel University, Kiel, Germany.

Abstract

Inflammation is a strong driver of atherosclerotic cardiovascular disease (ASCVD). There is a large unmet need for therapies that prevent or reduce excessive inflammation while avoiding systemic immunosuppression. We showed previously that selective inhibition of pro-inflammatory interleukin-6 (IL-6) trans-signalling by the fusion protein olamkicept (sgp130Fc) prevented and reduced experimental murine atherosclerosis in low-density lipoprotein receptor-deficient (Ldlr ^-/-) mice on a high-fat, high-cholesterol diet independently of low-density lipoprotein (LDL) cholesterol metabolism. Therefore, we allowed compassionate use of olamkicept (600 mg intravenously biweekly for 10 weeks) in a patient with very-high-risk ASCVD. Despite optimal LDL cholesterol under maximum tolerated lipid-lowering treatment, the patient had a remaining very high risk for future cardiovascular events related to significant arterial wall inflammation with lipoprotein (a) [Lp(a)]-cholesterol as the main contributor. ¹⁸Fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸FDG PET/CT) measurements were performed before and after the treatment period. Olamkicept reduced arterial wall inflammation in this patient without interfering with lipoprotein metabolism. No clinical or laboratory side effects were observed during or after treatment with olamkicept. Our findings in this patient matched the results from our mechanistic study in Ldlr ^-/- mice, which were extended by additional analyses on vascular inflammation. Olamkicept may be a promising option for treating ASCVD independently of LDL cholesterol metabolism. A Phase II trial of olamkicept in ASCVD is currently being prepared.

Keywords: atherosclerosis; case report; interleukin-6; olamkicept; sgp130Fc.

Publication types

Case Reports