# John J.P. Kastelein
**John J.P. Kastelein** is a Dutch vascular medicine specialist and lipidologist, Emeritus Professor of Medicine at the Department of Vascular Medicine of Amsterdam UMC (formerly the Academic Medical Center) of the [University of Amsterdam](https://www.edgepedia.org/university-of-amsterdam), where he held the Strategic Chair of Genetics of Cardiovascular Disease.[1](https://esc365.escardio.org/person/24778) He is known for genetic studies of familial hypercholesterolemia and for serving on the steering committees of major lipid-lowering trials, including the ORION program of inclisiran trials.[2](https://www.matinasbiopharma.com/about-us/leadership/member/2147/john-j-p-kastelein-m-d-ph-d-fesc) Amsterdam UMC lists him as Prof. MD PhD, Full Professor of Vascular Medicine, with research expertise in the pathogenesis of atherosclerosis and treatment of increased cardiovascular risk.[3](https://pure.amsterdamumc.nl/en/persons/john-kastelein/)
| Key facts | |
|---|---|
| Field | Vascular medicine, lipidology, genetics of cardiovascular disease[3](https://pure.amsterdamumc.nl/en/persons/john-kastelein/) |
| Position | Emeritus Professor of Medicine, Department of Vascular Medicine, Amsterdam UMC, University of Amsterdam[1](https://esc365.escardio.org/person/24778) |
| Training | [4](https://www.termedia.pl/pobierz/06728726ca8fe83939ddad0b8229e022) |
| FH program | Co-founded the Dutch StoeH screening program, which has produced over 18,000 molecular familial hypercholesterolemia diagnoses[5](https://eas-society.org/page/anitschkow-prize-recipient-2014/) |
| Inclisiran | Led the ORION program: at day 510, LDL cholesterol reductions from baseline of 39.7% in heterozygous FH (ORION-9), with a between-group difference of −47.9 percentage points versus placebo, and of 52.3% and 49.9% in ORION-10 and ORION-11 |[6](https://www.nejm.org/doi/full/10.1056/NEJMoa1913805) • [7](https://pubmed.ncbi.nlm.nih.gov/32187462/)
| Signature work | "Two Phase 3 Trials of Inclisiran in Patients with Elevated LDL Cholesterol" and "Inclisiran for the Treatment of Heterozygous Familial Hypercholesterolemia", both in the New England Journal of Medicine, 2020[7](https://pubmed.ncbi.nlm.nih.gov/32187462/) • [6](https://www.nejm.org/doi/full/10.1056/NEJMoa1913805); ["Association of LDL Cholesterol, Non–HDL Cholesterol, and Apolipoprotein B Levels With Risk of Cardiovascular Events Among Patients Treated W"](https://doi.org/10.1001/jama.2012.366), *JAMA*, 2012 |
| Industry roles | Co-founder of Xenon Pharma, UniQure, Dezima, and NewAmsterdam Pharma, where he became Chief Scientific Officer[8](https://forbion.com/team/john-jp-kastelein-md-phd-fesc/) |
| Honors | EAS Anitschkow Prize 2014; Dutch Heart Association prize of EUR 1 million, 2010; ZonMw Parel, 2011; Fellow of the European Society of Cardiology[5](https://eas-society.org/page/anitschkow-prize-recipient-2014/) • [8](https://forbion.com/team/john-jp-kastelein-md-phd-fesc/) |
## Training and career
Between 1986 and 1988 he trained in medical genetics, lipidology, and molecular biology at the [University of British Columbia](https://www.edgepedia.org/university-of-british-columbia) in Vancouver. He received his doctorate from the University of Amsterdam in 1991 cum laude for the thesis *The Molecular Basis of Inherited Disorders of Lipoprotein Metabolism*.[4](https://www.termedia.pl/pobierz/06728726ca8fe83939ddad0b8229e022)
In 1989 he founded the Lipid Research Clinic at the Academic Medical Centre in Amsterdam.[2](https://www.matinasbiopharma.com/about-us/leadership/member/2147/john-j-p-kastelein-m-d-ph-d-fesc) He became co-chairman of the Vascular Medicine subdepartment of AMC-UvA in 1999[9](https://www.uva.nl/content/nieuws/hoogleraarsbenoemingen/2002/12/dhr-dr-j-j-p-kastelein.html) and was appointed professor of internal medicine at the University of Amsterdam effective 1 January 2003.[9](https://www.uva.nl/content/nieuws/hoogleraarsbenoemingen/2002/12/dhr-dr-j-j-p-kastelein.html) He later became Emeritus Professor of Medicine at the same department.[1](https://esc365.escardio.org/person/24778)
## Familial hypercholesterolemia and the Amsterdam lipid clinic
According to the European Atherosclerosis Society, in 1995 Kastelein helped set up the Dutch StoeH foundation for identifying FH patients, now supervised by the RIVM; since its inception the program has found over 18,000 individuals with a molecular diagnosis of FH.[5](https://eas-society.org/page/anitschkow-prize-recipient-2014/) The "extreme genetics" approach he developed with Dr. Hayden holds that rare disorders with premature coronary disease point to therapeutic targets valid for all patients; the EAS credits it with supporting the discovery of ABCA1 and gene therapy for lipoprotein lipase deficiency.[5](https://eas-society.org/page/anitschkow-prize-recipient-2014/)
The Lipid Research Clinic he founded in 1989 serves as a tertiary referral center for over 5,000 patients each year and became part of the Department of Vascular Medicine.[2](https://www.matinasbiopharma.com/about-us/leadership/member/2147/john-j-p-kastelein-m-d-ph-d-fesc) His Amsterdam clinic is described as the largest pediatric lipid clinic in the world, and his group has seen over 2,000 children with heterozygous FH.[10](https://peterattiamd.com/johnkastelein/)
## Representative work
Two 2020 reports in the *New England Journal of Medicine* stand for his trial leadership. ["Two Phase 3 Trials of Inclisiran in Patients with Elevated LDL Cholesterol"](https://doi.org/10.1056/nejmoa1912387) reported the ORION-10 and ORION-11 trials, which randomized 1,561 and 1,617 patients with elevated LDL cholesterol despite maximum tolerated statin therapy; at day 510, inclisiran reduced LDL cholesterol by 52.3% and 49.9% respectively versus placebo (both P<0.001).[7](https://pubmed.ncbi.nlm.nih.gov/32187462/) According to the *Two Phase 3 Trials of Inclisiran in Patients with Elevated LDL Cholesterol* (N Engl J Med, 2020), inclisiran 284 mg was given by subcutaneous injection on day 1, day 90, and every 6 months thereafter; injection-site reactions were more frequent with the drug (about 2.6% versus roughly 1% in ORION-10; nearly 5% versus 0.5% in ORION-11) and none were severe or persistent.[7](https://pubmed.ncbi.nlm.nih.gov/32187462/) [[Inclisiran](https://www.edgepedia.org/inclisiran) for the Treatment of Heterozygous Familial Hypercholesterolemia reported ORION-9, a phase 3 trial of about 400 participants funded by the Medicines Company; at day 510 the LDL cholesterol change was a reduction of 39.7% with inclisiran versus an 8.2% increase with placebo, a between-group difference of −47.9 percentage points.[6](https://www.nejm.org/doi/full/10.1056/NEJMoa1913805) • [11](https://clinicaltrials.gov/study/NCT03397121) Inclisiran itself is a chemically synthesized siRNA molecule that produces sustained, hepatocyte-specific silencing of PCSK9 RNA.[12](https://www.nejm.org/doi/full/10.1056/NEJMoa1615758)
His steering-committee record spans the SPIRE, ORION, GLAGOV, REALIZE, IDEAL, TNT, CAPTIVATE, ENHANCE, ILLUMINATE, JUPITER, and RADIANCE trials.[2](https://www.matinasbiopharma.com/about-us/leadership/member/2147/john-j-p-kastelein-m-d-ph-d-fesc) Among his widely cited reviews are [a 2012 JAMA analysis](https://doi.org/10.1001/jama.2012.366) of LDL cholesterol, non-HDL cholesterol, and apolipoprotein B as predictors of cardiovascular events in statin-treated patients, and [a 2014 review](https://doi.org/10.1016/j.jacc.2014.02.615) in the *Journal of the American College of Cardiology* on very low levels of atherogenic lipoproteins and cardiovascular risk.
## Industry ties and honors
Kastelein co-founded Xenon Pharma, UniQure, Dezima, and [NewAmsterdam Pharma](https://www.edgepedia.org/newamsterdam-pharma), where he became Chief Scientific Officer.[8](https://forbion.com/team/john-jp-kastelein-md-phd-fesc/) He is an Operating Partner at Forbion, advising on cardiovascular and metabolic disease investment opportunities.[8](https://forbion.com/team/john-jp-kastelein-md-phd-fesc/) He became acting Chief Medical Officer of Statin Biotechnology Inc., developing an antibody against apolipoprotein C-III, and CEO of the Vascular Research Network, a site organization of over 50 Dutch hospitals.[13](https://northseatherapeutics.com/en/about_us/our_team/238/prof_john_kastelein/) Dezima developed the CETP inhibitor TA-8995.[5](https://eas-society.org/page/anitschkow-prize-recipient-2014/)
He received the EAS Anitschkow Prize in 2014,[5](https://eas-society.org/page/anitschkow-prize-recipient-2014/) the Dutch Heart Association prize of EUR 1 million in 2010, and the ZonMw Parel in 2011 for gene therapy research; he is a Fellow of the [European Society of Cardiology](https://www.edgepedia.org/european-society-of-cardiology).[8](https://forbion.com/team/john-jp-kastelein-md-phd-fesc/) He was president of the Dutch Atherosclerosis Society, chaired the National Scientific Committee on Familial Hypercholesterolemia, and was appointed to the Executive Board of the International Atherosclerosis Society.[5](https://eas-society.org/page/anitschkow-prize-recipient-2014/)
## Recent work
Kastelein remains active in CETP inhibition through NewAmsterdam Pharma, whose drug obicetrapib is a highly selective CETP inhibitor that reduces LDL cholesterol. The obicetrapib phase 3 trial in patients with heterozygous FH or atherosclerotic cardiovascular disease on maximum tolerated statin therapy was published in the *New England Journal of Medicine* in 2025, supported by NewAmsterdam Pharma with Kastelein among the authors.[14](https://doi.org/10.1056/nejmoa2415820) A pooled analysis of obicetrapib's effect on major adverse cardiovascular events followed in the *Journal of the American College of Cardiology* (86(14):1046–1056, 2025); its disclosure statement lists Kastelein as an employee of NewAmsterdam Pharma holding stocks or options.[15](https://pure.amsterdamumc.nl/ws/files/157362172/Impact-of-obicetrapib-on-major-adverse-cardiovascular-events-in-high-risk-patients.pdf) At ESC Congress 2024, on 30 August 2024, he presented on CETP inhibition genetics and biology in a session on CETP as a therapeutic target for LDL-cholesterol management.[16](https://esc365.escardio.org/presentation/289171) According to the European Atherosclerosis Society's AtheroTalk page, in 2026 the society featured him in its AtheroTalk series discussing the evolution of lipid-lowering therapy from the early statin era to today's treatments.[17](https://eas-society.org/2026/atherotalk-john-j-p-kastelein/)
## References
1. ESC 365, Professor John Kastelein (biography), https://esc365.escardio.org/person/24778
2. John J.P. Kastelein, Matinas BioPharma leadership page, https://www.matinasbiopharma.com/about-us/leadership/member/2147/john-j-p-kastelein-m-d-ph-d-fesc
3. John Kastelein, Amsterdam UMC Pure profile, https://pure.amsterdamumc.nl/en/persons/john-kastelein/
4. Johannes J.P. Kastelein (CV), https://www.termedia.pl/pobierz/06728726ca8fe83939ddad0b8229e022
5. Anitschkow Prize Recipient 2014, European Atherosclerosis Society, https://eas-society.org/page/anitschkow-prize-recipient-2014/
6. Inclisiran for the Treatment of Heterozygous Familial Hypercholesterolemia (NEJM), https://www.nejm.org/doi/full/10.1056/NEJMoa1913805
7. Two Phase 3 Trials of Inclisiran in Patients with Elevated LDL Cholesterol (PubMed), https://pubmed.ncbi.nlm.nih.gov/32187462/
8. John J.P. Kastelein, MD PhD FESC, Operating Partner, Forbion, https://forbion.com/team/john-jp-kastelein-md-phd-fesc/
9. Dhr. dr. J.J.P. Kastelein, Universiteit van Amsterdam, https://www.uva.nl/content/nieuws/hoogleraarsbenoemingen/2002/12/dhr-dr-j-j-p-kastelein.html
10. John Kastelein on the Peter Attia MD podcast, https://peterattiamd.com/johnkastelein/
11. ORION-9 (NCT03397121), ClinicalTrials.gov, https://clinicaltrials.gov/study/NCT03397121
12. Inclisiran in Patients at High Cardiovascular Risk with Elevated LDL Cholesterol (NEJM), https://www.nejm.org/doi/full/10.1056/NEJMoa1615758
13. Prof. John Kastelein, NorthSea Therapeutics, https://northseatherapeutics.com/en/about_us/our_team/238/prof_john_kastelein/
14. Safety and Efficacy of Obicetrapib in Patients at High Cardiovascular Risk (NEJM, 2025), https://doi.org/10.1056/nejmoa2415820
15. Impact of Obicetrapib on Major Adverse Cardiovascular Events in High-Risk Patients: A Pooled Analysis (JACC, 2025), https://pure.amsterdamumc.nl/ws/files/157362172/Impact-of-obicetrapib-on-major-adverse-cardiovascular-events-in-high-risk-patients.pdf
16. ESC Congress 2024, CETP as a therapeutic target, https://esc365.escardio.org/presentation/289171
17. AtheroTalk: John J.P. Kastelein, EAS, 2026, https://eas-society.org/2026/atherotalk-john-j-p-kastelein/
---
*Topic: Encyclopedia › Life and health › Life and health scientists › Medical and health researchers › Researchers in cardiovascular, metabolic, and endocrine research › Lipid metabolism and hyperlipidemia*
*Initially written Sep 20, 2026 · Reviewed: Sep 25, 2026; Sep 30, 2026 · Edited: Sep 25, 2026; Sep 30, 2026; Oct 15, 2026; Oct 21, 2026 · Last review: Sep 30, 2026*
*Copyright 2026 EdgeChat AI, a subsidiary of Biostate AI.*
License: Edgepedia Community License 1.0, https://www.edgepedia.org/edgepedia/license