{"entity":{"id":"orteronel","kind":"drug","name":"Orteronel","aka":["TAK-700"],"tldr":"A more selective version of abiraterone that was meant to avoid the need for steroids. It delayed the cancer on scans but did not help men live longer, and was abandoned.","summary":"Orteronel is a non-steroidal, partially selective inhibitor of CYP 17,20-lyase. The selectivity was the point: abiraterone inhibits both the 17-alpha-hydroxylase and the 17,20-lyase activities of CYP17, which is why it raises mineralocorticoids and has to be given with a corticosteroid. A lyase-selective inhibitor should avoid that.\n\nELM-PC 4 randomised 1,560 chemotherapy-naive men with metastatic castration-resistant prostate cancer at 324 centres in 43 countries to orteronel 400 mg with prednisone twice daily or placebo with prednisone. Median radiographic progression-free survival was 13.8 months against 8.7, hazard ratio 0.71 (95 percent confidence interval 0.63 to 0.80, p<0.0001), a large and unambiguous effect. Median overall survival was 31.4 against 29.5 months, hazard ratio 0.92 (0.79 to 1.08, p=0.31), which is nothing. The companion trial in men after docetaxel, ELM-PC 5, also missed overall survival.\n\nGrade 3 or worse increases in lipase (17 against 2 percent) and amylase (10 against 1 percent) were the characteristic toxicities, along with fatigue and pulmonary embolism. Millennium, a Takeda subsidiary, stopped developing the drug. Orteronel is the reason the field treats radiographic progression-free survival in prostate cancer with suspicion as a surrogate for survival.","status":"withdrawn","asOf":"2026-09-25","links":[{"label":"ELM-PC 4 (Lancet Oncology 2015)","url":"https://doi.org/10.1016/S1470-2045(15)70027-6"}],"tags":[],"related":[],"cancers":["prostate","prostate-mcrpc"],"sections":[],"technologies":[],"targets":["cyp17a1"],"drugs":[],"companies":["takeda"],"institutions":[],"pathways":[],"terms":["arpi","castration-resistance"],"trials":["elm-pc-4-orteronel"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"code":"TAK-700","modality":"small molecule","mechanism":"Non-steroidal, partially selective inhibitor of CYP 17,20-lyase, reducing extragonadal androgen synthesis.","approvals":[],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[]},"route":"/drugs/orteronel/","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/"}],"target":[{"id":"cyp17a1","kind":"target","name":"CYP17A1 (17-alpha-hydroxylase/17,20-lyase)","route":"/targets/cyp17a1/"}],"company":[{"id":"takeda","kind":"company","name":"Takeda","route":"/companies/takeda/"}],"term":[{"id":"arpi","kind":"term","name":"Androgen receptor pathway inhibitor (ARPI)","route":"/terms/arpi/"},{"id":"castration-resistance","kind":"term","name":"Castration-resistant prostate cancer (CRPC)","route":"/terms/castration-resistance/"}],"trial":[{"id":"elm-pc-4-orteronel","kind":"trial","name":"ELM-PC 4","route":"/trials/elm-pc-4-orteronel/"}]}}