PCSK9 proprotein convertase subtilisin/kexin type 9
ENSG00000169174 · protein coding · Open Targets profile
Crucial player in the regulation of plasma cholesterol homeostasis. Binds to low-density lipid receptor family members: low density lipoprotein receptor (LDLR), very low density lipoprotein receptor (VLDLR), apolipoprotein E receptor (LRP1/APOER) and apolipoprotein receptor 2 (LRP8/APOER2), and promotes their degradation in intracellular acidic compartments (PubMed:18039658). Acts via a non- proteolytic mechanism to enhance the degradation of the hepatic LDLR through a clathrin LDLRAP1/ARH-mediated pathway. May prevent the recycling of LDLR from endosomes to the cell surface or direct it to lysosomes for degradation. Can induce ubiquitination of LDLR leading to its subsequent degradation (PubMed:17461796, PubMed:18197702, PubMed:18799458, PubMed:22074827). Inhibits intracellular degradation of APOB via the autophagosome/lysosome pathway in a LDLR-independent manner. Involved in the disposal of non-acetylated intermediates of BACE1 in the early secretory pathway (PubMed:18660751). Inhibits epithelial Na(+) channel (ENaC)-mediated Na(+) absorption by reducing ENaC surface expression primarily by increasing its proteasomal degradation. Regulates neuronal apoptosis via modulation of LRP8/APOER2 levels and related anti-apoptotic signaling pathways. {ECO:0000269|PubMed:17461796, ECO:0000269|PubMed:18039658, ECO:0000269|PubMed:18197702, ECO:0000269|PubMed:18660751, ECO:0000269|PubMed:18799458, ECO:0000269|PubMed:22074827, ECO:0000269|PubMed:22493497, ECO:0000269|PubMed:22580899}.
Each band is a group of drugs. It runs from the kind of drug on the left to the furthest stage that drug has reached in any disease on the right. Thicker bands mean more drugs.
Approved bands are highlighted. Withdrawn means the drug was pulled from the market or from development. A combined phase counts as the later one (Phase 1/2 is shown as Phase 2). Hover a band for the drug names. Source: Open Targets Platform, fetched live.
Each row is a cancer, strongest overall evidence first. The two dots show how strong the inherited (germline) and tumour-mutation (somatic) evidence is; the line between them is the gap.
Scores run from 0 (no evidence) to 1 (strongest). A missing dot at 0 means Open Targets holds no evidence of that kind. Source: Open Targets Platform, fetched live.
Tractability
- Small molecule
- Structure with Ligand, High-Quality Ligand, High-Quality Pocket
- Antibody
- Approved Drug, GO CC high conf, UniProt loc med conf, UniProt SigP or TMHMM
- PROTAC
- Database Ubiquitination, Small Molecule Binder
- Other modalities
- Advanced Clinical
gnomAD loss of function constraint: o/e 0.917639970779419 (upper bound 1.1440999507904053). Low values mean loss of function is poorly tolerated, a safety flag for inhibition.
Who runs trials of these drugs
Principal investigators and study chairs on 142 registry trials, updated in the last three years, of the most advanced drugs against PCSK9 (inclisiran, alirocumab, evolocumab, bococizumab, lerodalcibep, ongericimab, tafolecimab, frovocimab), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- David KallendLIB Therapeutics · 3 of 3 trials Phase 2+
- Evan A SteinLIB Therapeutics · 3 of 3 trials Phase 2+
- Yong HuoPeking University First Hospital · 2 of 2 trials Phase 2+
- Zhijian WangBeijing Anzhen Hospital · 2 of 2 trials Phase 2+
- Alexandra ErshovaNational Medical Research Centre for Therapy and Preventive Medicine Ministry of Health of Russia · 1 of 2 trials Phase 2+
- Yong HeWest China Hospital · 1 of 2 trials Phase 2+
- Yongjun WangBeijing Tiantan Hospital · 1 of 2 trials Phase 2+
- Anil K ChandrakerBrigham and Women's Hospital · 1 of 1 trials Phase 2+
- Antoinette BirsUniversity of California, San Diego · 1 of 1 trials Phase 2+
- Bo HuUnion Hospital, Tongji Medical College, Huahzong University of Science and Technology · 1 of 1 trials Phase 2+
- Candong HongUnion Hospital, Tongji Medical College, Huahzong University of Science and Technology · 1 of 1 trials Phase 2+
- China JiangsuNanjin First Hospital,Nanjing Medical University · 1 of 1 trials Phase 2+
- Daniel S. BermanCedars-Sinai Medical Center · 1 of 1 trials Phase 2+
- David MazerUnity Health Toronto · 1 of 1 trials Phase 2+
- David PreissUniversity of Oxford · 1 of 1 trials Phase 2+
Registry trials of inclisiran, alirocumab, evolocumab, bococizumab, lerodalcibep, ongericimab, tafolecimab, frovocimab updated in the last three years, counted by the country group of their listed sites. A trial with sites in several groups counts in each; 100 of 133 have all sites in one country.
Site counts are not patients per country, and trials registered only outside ClinicalTrials.gov are not covered. Where sites are is a fact about the record, not a judgement of its quality. Europe is the EU and EEA, the UK and Switzerland. 9 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
28 trials of drugs against PCSK9 were stopped early; 1 give no reason
Terminated, withdrawn and suspended interventional trials of inclisiran, alirocumab, evolocumab, bococizumab, lerodalcibep, ongericimab, tafolecimab, frovocimab, ralpancizumab, newest update first, live from ClinicalTrials.gov. Each reason is quoted exactly as the registry gives it; we do not sort reasons into safety, efficacy or business. Dates are the last registry update. Showing the 25 most recent of 28.
- terminated · 2026-09-23 · Beijing Inno Medicine Co., Ltd. · Evolocumab“The study was terminated at the request of the Sponsor.”
- terminated · 2026-05-22 · Henan Institute of Cardiovascular Epidemiology · Evolocumab 140 mg/1 ml Subcutaneous Solution [REPATHA]“Slow patient enrollment and lack of financial support”
- terminated · 2026-05-12 · Hoffmann-La Roche · Evolocumab“Study was closed early as the sponsor decided not to continue development of certain treatment combinations.”
- terminated · 2026-05-05 · Eziafa Oduah, MD, PhD, MPH · Evolocumab“Slow enrollment.”
- withdrawn · 2025-03-17 · University of Louisville · matched by the registry's drug synonyms“study withdrawn, no participants enrolled, changes in the study design planned”
- terminated · 2025-01-27 · Monash University · matched by the registry's drug synonyms“Loss of strategic interest by the funding party. The participants' recruitment rate failed to meet the target within the pre-specified recruitment windows.”
- withdrawn · 2024-11-21 · Fondazione IRCCS Policlinico San Matteo di Pavia · Evolocumab“The sponsor required early termination of the economic agreement due to a supposed extension of the enrollment period for bureaucracy reasons and for the concomitant Covid -19 Pandemic”
- terminated · 2024-08-06 · Imperial College London · Evolocumab“Funding withdrawn”
- terminated · 2024-05-29 · Amgen · Evolocumab“Amgen business decision to close study early”
- terminated · 2024-05-16 · University Hospital Tuebingen · matched by the registry's drug synonyms“poor recruitment”
- terminated · 2023-03-27 · Amgen · evolocumab“Prematurely Discontinued Amgen decision”
- terminated · 2023-03-15 · University of California, Los Angeles · matched by the registry's drug synonyms“Funding Discontinued”
- terminated · 2023-01-19 · Inova Health Care Services · Evolocumab“Low enrollment”
- terminated · 2022-08-19 · Gloria Vega · Alirocumab, Alirocumab placebo“Difficult recruitment”
- withdrawn · 2022-07-28 · NYU Langone Health · Evolocumab“loss of funding”
- terminated · 2021-09-16 · Minneapolis Heart Institute Foundation · Alirocumab 150 MG/ML subcutaneous injection“Withdrawal of medication and funding support by Sponsor”
- terminated · 2021-06-15 · Regeneron Pharmaceuticals · matched by the registry's drug synonyms“The primary objective (to evaluate the long-term safety of Praluent) was adequately evaluated in other studies.”
- terminated · 2021-04-01 · Columbia University · Evolocumab“Terminated Prematurely due to COVID-19”
- withdrawn · 2020-10-14 · Copenhagen University Hospital, Rigshospitalet · Evolocumab or Alirocumab“Logistic reasons”
- terminated · 2020-04-24 · Medical University of Graz · matched by the registry's drug synonyms“COVID-19 Pandemic Measures”
- terminated · 2020-04-21 · University of Utah · Alirocumab“Funding withdrawn”
- withdrawn · 2019-12-06 · ECRI bv · Evolocumab“Admisnitrative issues”
- terminated · 2019-06-19 · University of California, San Francisco · Bococizumab“Industry won't be moving forward with production of bococizumab”
- withdrawn · 2019-06-13 · Imperial College London · Alirocumab“Changes in funding decision”
- terminated · 2019-05-01 · Pfizer · bococizumab (PF-04950615)“See Detailed Description”
Paediatric incentives and obligations for PCSK9's drugs
For inclisiran, alirocumab, evolocumab, bococizumab, lerodalcibep, ongericimab, tafolecimab, frovocimab, ralpancizumab: what EMA and FDA publish about paediatric plans, orphan status and pediatric approvals, and how many registered studies take children. Each line is a yes, no or not published fact from the record linked under it; none of it is a forecast.
- FDA pediatric target list: no · PCSK9 is not on the listRule: Target is on FDA's Pediatric Molecular Target List (relevant targets). Source: FDA Pediatric Molecular Target List (Listed as February 2026 on the FDA Pediatric Oncology page; the file served is 9.7.22_the_relevant_molecular_target_list.xlsx, whose Summary of Changes sheet is headed 'SEPTEMBER 2022 UPDATE' (footnote date 2022-09-01)), 2026-11-11
- EU paediatric investigation plan: yes · EMA/PE/0000242923 (Lerodalcibep, Treatment of hypercholesterolaemia): PM: decision on the application for modification of an agreed PIP, 5 May 2025; EMEA-001169-PIP01-11-M05 (alirocumab, Treatment of elevated cholesterol): PM: decision on the application for modification of an agreed PIP, 31 Dec 2021; compliance positive 24 Feb 2023; EMEA-002214-PIP01-17-M02 (Inclisiran sodium, Treatment of elevated cholesterol): PM: decision on the application for modification of an agreed PIP, 11 Aug 2023; EMEA-001268-PIP01-12-M05 (Evolocumab, Treatment of elevated cholesterol;Treatment of mixed dyslipidaemia): PM: decision on the application for modification of an agreed PIP, 11 Apr 2018; compliance positive 24 Jun 2022; +1 moreRule: An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name. Source: EMA data download (dated snapshot), 2026-11-11
- EU orphan designation: no · No EU orphan designation names inclisiran, alirocumab, evolocumab, bococizumab, lerodalcibep, ongericimab, tafolecimab, frovocimab, ralpancizumabRule: An EU orphan designation lists the drug as its active substance (exact name) or belongs to a medicine that does; withdrawn and expired designations are listed with their status. Source: EMA data download (dated snapshot), 2026-11-11
- Authorised in the EU: yes · Leqvio: authorised since 9 Dec 2020; Repatha: authorised since 17 Jul 2015; Lyrokaul: opinion; Praluent: authorised since 23 Sept 2015Rule: An EMA medicine record lists the drug as its active substance or INN, exact name; national-only authorisations are not in this file. Source: EMA data download (dated snapshot), 2026-11-11
- FDA orphan designation: not published · FDA's orphan designation database turns away automated requests, so this app does not read it; search it by hand at the linkRule: Would be: an FDA orphan designation names the drug. Source: FDA orphan designations search
- FDA pediatric oncology approval: no · FDA's table lists no pediatric approval of inclisiran, alirocumab, evolocumab, bococizumab, lerodalcibep, ongericimab, tafolecimab, frovocimab, ralpancizumabRule: FDA's Pediatric Oncology Drug Approvals table names the drug. Source: FDA Pediatric Oncology Drug Approvals (content current as of 2026-03-03), 2026-11-12
- Registered studies open to children: yes · 21 interventional studies of inclisiran, alirocumab, evolocumab, bococizumab, lerodalcibep, ongericimab, tafolecimab, frovocimab, ralpancizumab include patients under 18; 5 are recruiting, not yet recruiting or activeRule: The registry's age group includes Child (birth to 17 years), which also counts studies that set no minimum age. Source: ClinicalTrials.gov search, 2026-11-12
Rare pediatric disease voucher. FDA, content current as of 29 Apr 2026: “As of February 3, 2026, enactment of the Consolidated Appropriations Act, 2026, the rare pediatric disease PRV program will sunset after September 30, 2029. FDA may not award any PRVs under this program after September 30, 2029.” Voucher sale prices are not shown here; they appear only as company-reported news. FDA: Rare Pediatric Disease Designation and Priority Review Voucher Programs
All 10 drugs and clinical candidates as a table
Each drug, stage and indication links to its Open Targets record, where the trials and approvals behind it are listed. Salt forms (for example a mesylate) are listed as Open Targets records them, as separate entries.