{"entity":{"id":"custirsen","kind":"drug","name":"Custirsen","aka":["OGX-011","TV-1011"],"tldr":"A drug designed to switch off a protein that helps cancer cells survive chemotherapy. Two large trials found it added nothing.","summary":"Clusterin is a chaperone protein that rises after apoptotic stress, including chemotherapy, and is associated with treatment resistance. Custirsen is a second-generation antisense oligonucleotide that blocks its production, and the hypothesis was that it would re-sensitise prostate cancer to taxanes.\n\nA randomised phase 2 trial (CUOG P-06c, 42 men) reported encouraging pain responses and a correlation between low serum clusterin during treatment and survival, which was enough to justify two phase 3 trials. Both failed. SYNERGY added custirsen to first-line docetaxel in 1,022 men and found median survival 23.4 against 22.0 months, hazard ratio 0.93 (95 percent confidence interval 0.79 to 1.10, p=0.415). AFFINITY added it to cabazitaxel after docetaxel in 635 men and found 14.1 against 13.4 months, hazard ratio 0.95 (0.80 to 1.12, p=0.53), with no benefit in the prespecified poor-prognosis subgroup either.\n\nOncoGenex, which developed it, is now Achieve Life Sciences and no longer works on cancer. The drug is a clean example of a biomarker association, serum clusterin and survival, that did not survive as a therapeutic target.","status":"withdrawn","asOf":"2026-09-25","links":[{"label":"SYNERGY (Lancet Oncology 2017)","url":"https://doi.org/10.1016/S1470-2045(17)30168-7"},{"label":"AFFINITY (Lancet Oncology 2017)","url":"https://doi.org/10.1016/S1470-2045(17)30605-8"}],"tags":[],"related":[],"cancers":["prostate","prostate-mcrpc"],"sections":[],"technologies":["antisense-sirna"],"targets":[],"drugs":[],"companies":["achieve-life-sciences"],"institutions":[],"pathways":[],"terms":["castration-resistance"],"trials":["synergy-custirsen","affinity-custirsen"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"code":"OGX-011","modality":"antisense oligonucleotide","mechanism":"Second-generation antisense oligonucleotide that inhibits production of the chaperone protein clusterin.","approvals":[],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[]},"route":"/drugs/custirsen/","neighbours":{"cancer":[{"id":"prostate-mcrpc","kind":"cancer","name":"Metastatic castration-resistant prostate cancer","route":"/cancers/prostate-mcrpc/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"}],"technology":[{"id":"antisense-sirna","kind":"technology","name":"Oligonucleotide therapeutics","route":"/technologies/antisense-sirna/"}],"company":[{"id":"achieve-life-sciences","kind":"company","name":"Achieve Life Sciences (formerly OncoGenex)","route":"/companies/achieve-life-sciences/"}],"term":[{"id":"castration-resistance","kind":"term","name":"Castration-resistant prostate cancer (CRPC)","route":"/terms/castration-resistance/"}],"trial":[{"id":"affinity-custirsen","kind":"trial","name":"AFFINITY","route":"/trials/affinity-custirsen/"},{"id":"synergy-custirsen","kind":"trial","name":"SYNERGY","route":"/trials/synergy-custirsen/"}]}}