Delving into the Latest Updates on Orteronel with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Orteronel (JAN/USAN), TAK-700

Target

CYP17A1

Mechanism

CYP17A1 inhibitors(Steroid 17-alpha-hydroxylase inhibitors)

Therapeutic Areas

NeoplasmsUrogenital Diseases

Active Indication

Castration-sensitive prostate cancerProstatic cancer metastaticProstatic Cancer

Inactive Indication

Adenocarcinoma of prostateBone metastasesCastration-Resistant Prostatic Cancer+ [4]

Originator Organization

Takeda Pharmaceutical Co., Ltd.

Active Organization

Radiation Therapy Oncology Group

National Cancer Institute

Millennium Pharmaceuticals, Inc.

Inactive Organization

Takeda Pharmaceutical Co., Ltd.

Excel Pharma Studies, Inc.Swiss Group for Clinical Cancer Research

+ [2]

Drug Highest PhasePhase 3

First Approval Date-

Regulation-

Structure

Molecular FormulaC18H17N3O2

InChIKeyOZPFIJIOIVJZMN-SFHVURJKSA-N

CAS Registry566939-85-3

The main object of this multicenter, randomized, double-blind, placebo-controlled phase III trial is to assess impact of maintenance of orteronel on disease progression and hence on quality of life of patients with metastatic castration resistant prostate cancer pretreated with novel hormonal agents who have non-progressive disease after chemotherapy with a taxane.

Start Date19 Aug 2014

Sponsor / Collaborator

Swiss Group for Clinical Cancer Research

NCT02101684 / TerminatedPhase 2IIT

Open Label Phase II Clinical Trial of Orteronel (TAK-700) in Metastatic or Advanced Non-resectable Granulosa Cell Ovarian Tumors. The Greko II Study.

Granulosa Cell ovarian carcinoma is an infrequent subtype of neoplasia well differentiated from epithelial tumors. They account for 5% of all ovarian malignancies and, with an incidence of 0.4-1.2 cases per 100000 habitants, is considered as a rare disease.
Though most cases are identified at initial stages and can be cured through surgical resection, distant recurrences have been documented even 10 years after resecting the primary tumor. At advanced stage it is a lethal disease.
Unfortunately because of the low incidence of this disease randomized clinical trials are lacking. In fact current evidence for treatment is provided by case reports, retrospective studies and phase II clinical trials performed one decade ago.
Orteronel, a novel, orally active, selective inhibitor of 17,20-lyase, is being developed as an endocrine therapy for relevant hormone-sensitive cancers such as prostate cancer and breast cancer. Orteronel is expected to suppress sex hormone levels in both circulation and relevant hormone-dependent malignant tissue. Since sex hormone overproduction has been demonstrated in granulosa cell ovarian tumors and seems to play a major role in this disease, this study will assess the efficacy or orteronel treating such tumors.

Start Date01 Jun 2014

Sponsor / Collaborator

Takeda Pharmaceutical Co., Ltd.

NCT02054793 / WithdrawnPhase 1/2IIT

Phase Ib/II Study Evaluating Orteronel (Without Prednisone) Combined With Itraconazole In Men With Castration-Resistant Prostate Cancer (CRPC)

This research is being done to test the safety and anti-cancer activity of the combination of an investigational drug called orteronel, with a drug called itraconazole in the treatment of castration-resistant prostate cancer.
Orteronel is an investigational drug known as a 17,20-lyase enzyme inhibitor, meaning that it blocks the formation of male sex hormones.
Itraconazole is approved by the Food and Drug Administration (FDA) for the treatment of various fungal infections such as fingernail/toenail infections and other more serious fungal infections. While it has shown evidence of activity against prostate cancer in prior studies, it is not approved for use in cancer. The FDA is allowing the use of orteronel and itraconazole in this research study. In addition to its antifungal properties, itraconazole was discovered to function to block angiogenesis (blood vessel formation to tumors) to block a cellular pathway thought to be important in prostate cancer known as the Hedgehog pathway.
Investigators hypothesize that blocking male sex hormone production with orteronel will increase reliance on the Hedgehog pathway in prostate cancer cells which can then be blocked with itraconazole and that the combination of these two drugs will be more effective than either alone.

Start Date01 Jun 2014

Sponsor / Collaborator

Millennium Pharmaceuticals, Inc.

100 Clinical Results associated with Orteronel

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100 Translational Medicine associated with Orteronel

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100 Patents (Medical) associated with Orteronel

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81

Literatures (Medical) associated with Orteronel

01 Feb 2024·European urology

Bone Biomarkers and Subsequent Survival in Men with Hormone-sensitive Prostate Cancer: Results from the SWOG S1216 Phase 3 Trial of Androgen Deprivation Therapy with or Without Orteronel

Article

Author: Goldkorn, Amir ; Gertz, Erik ; Twardowski, Przemyslaw ; Mayerson, Edward ; Lara, Primo N. Jr ; Agarwal, Neeraj ; Vogelzang, Nicholas J. ; Parikh, Mamta ; Tangen, Catherine ; van Loan, Marta ; Thompson, Ian ; Hussain, Maha ; Zhang, Jingsong ; Quinn, David I. ; Gupta, Shilpa ; LeBlanc, Michael

BACKGROUND:

Bone biomarkers are strongly prognostic for overall survival (OS) in men with castration-resistant prostate cancer but not fully established for hormone-sensitive prostate cancer (HSPC).

OBJECTIVE:

Bone biomarkers in HSPC were prospectively evaluated as part of a phase 3 study of androgen deprivation therapy ± the CYP17 inhibitor orteronel.

DESIGN, SETTING, AND PARTICIPANTS:

Patients were randomly divided into training (n = 316) and validation (n = 633) sets. Recursive partitioning and Cox proportional hazard models were employed.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:

Bone resorption (C-telopeptide and pyridinoline) and bone formation markers (C-terminal collagen propeptide and bone alkaline phosphatase) were assessed from patient sera.

RESULTS AND LIMITATIONS:

Of 1279 men, 949 had evaluable baseline bone biomarkers. Optimal cutoffs were identified to define elevated levels of each of the four biomarkers (all p < 0.05) that were associated with worse OS. After adjusting for clinical risk factors in the validation set, elevated bone biomarkers were statistically significantly associated with an increased risk of death (hazard ratios ranging from 1.37 to 1.92). Recursive partitioning algorithms applied to the training set identified three risk groups (low, intermediate, and poor) with differential OS outcomes (median OS: 8.2, 5.1, and 2.1 yr, respectively) based on combinations of bone biomarkers. These results were confirmed in the validation set.

CONCLUSIONS:

In men with HSPC initiating androgen deprivation therapy, bone biomarkers are strongly and independently prognostic for OS. Bone biomarker levels alone or in combination with clinical covariates identify unique subsets of men with differential OS outcomes. These results validate the clinical value of bone biomarker assessment in the HSPC state, extending bone biomarker utility beyond the castration-resistant state.

PATIENT SUMMARY:

In men with newly diagnosed metastatic prostate cancer, high levels of bone turnover biomarkers are associated with a shorter lifespan.

01 Sep 2023·Prostate international

Oral chemotherapeutic agents in metastatic hormone-sensitive prostate cancer: A network meta-analysis of randomized controlled trials.

Article

Author: Kim, Seong Hwan ; Chang, In Ho ; Kim, Myoungsuk ; Choi, Joongwon ; Myung, Soon Chul ; Kim, Tae-Hyoung ; Choi, Se Young ; Kim, Jung Hoon ; Kim, Jin Wook ; Lee, Yong Seong ; Tae, Jong Hyun ; Nguyen, Tuan Thanh

Background:

Multiple oral chemotherapeutic agents for metastatic hormone-sensitive prostate cancer (mHSPC) have been developed for conjugated use with conventional androgen deprivation therapy (ADT). Several randomized controlled trials (RCTs) report significant benefits in mHSPC patients. Therefore, we compared overall survival (OS) and progression-free survival (PFS) benefits among considerable mHSPC oral chemotherapeutic agents.

Materials and methods:

We investigated mHSPC treatment efficacy through a systematic RCT-trial literature review (PubMed, Embase, Web of Science, the Cochrane Library, and Scopus). Two reviewers independently screened, extracted data, and assessed bias risk in duplicate.

Results:

We identified 18 RCTs (n = 13,509). Concerning OS, ADT + abiraterone, ADT + abiraterone + docetaxel, ADT + apalutamide, ADT + bicalutamide, ADT + darolutamide + docetaxel, ADT + enzalutamide, ADT + orteronel, and ADT + rezvilutamide were more effective than the standard of care (SOC). Comparing PFS, most treatments were more effective than SOC, excluding ADT + bicalutamide, nilutamide, flutamide, ADT + bicalutamide + palbociclib, and ADT + nilutamide. ADT + docetaxel with androgen receptor targeted agent (ARTA) triplet therapy was not among the top three treatments determined through ranking analysis.

Conclusions:

Novel oral chemotherapeutic agent combination therapies must replace current ADT monotherapy and ADT + docetaxel SOC. Even so, ADT + docetaxel with ARTA triplet therapy still is not the best mHSPC treatment and requires further study.

01 Aug 2023·JAMA network open

Race and Treatment Outcomes in Patients With Metastatic Castration-Sensitive Prostate Cancer: A Secondary Analysis of the SWOG 1216 Phase 3 Trial.

Article

Author: Jo, Yeonjung ; Hussain, Maha H A ; Plets, Melissa ; Sayegh, Nicolas ; Thompson, Ian M ; Gebrael, Georges ; Haaland, Benjamin ; Gupta, Shilpa ; Quinn, David I ; Agarwal, Neeraj ; Lara, Primo N ; Swami, Umang

Importance:

Black patients present with more aggressive disease and experience higher mortality than White patients with prostate cancer. Race and social determinants of health influence prostate cancer-specific mortality and overall survival (OS); however, in a previous trial, Black patients did not have inferior outcomes compared with White patients, possibly because of equitable access to care available in a clinical trial setting.

Objective:

To compare differences in survival outcomes of patients with metastatic castration-sensitive prostate cancer (mCSPC) by race in a phase 3 trial with a large proportion of Black patients.

Design, Setting, and Participants:

This secondary analysis of patient-level data of a prospective phase 3 randomized clinical trial included patients with newly diagnosed mCSPC enrolled between March 1, 2013, and July 15, 2017. Analysis was conducted between December 2022 and February 2023.

Interventions:

Patients receiving androgen deprivation therapy were randomized (1:1) to receive either orteronel 300 mg orally twice daily (experimental group) or bicalutamide 50 mg orally daily (control group).

Main Outcomes and Measures:

OS, with progression-free survival (PFS) as a secondary end point.

Results:

Among 1313 participants, 135 (10%) identified as Black and 1077 (82%) as White, with an equal racial distribution between groups. Black patients were younger (median [IQR] age, 65.8 [60-70] vs 68.4 [62.5-74.1] years; P = .001) and had a higher median (IQR) baseline prostate-specific antigen response rate than White patients (54.7 [19.8-222.0] vs 26.7 [9.2-96.0] ng/mL; P < .001). At a median follow-up of 4.9 years, Black and White patients had similar median PFS (2.3 years; 95% CI, 1.8-1.4 years vs 2.9 years; 95% CI, 2.5-3.3 years; P = .71) and OS (5.5 years; 95% CI, 4.8-NR vs 6.3 years; 95% CI, 5.7-NR; P = .65). The multivariable analysis confirmed similar PFS and OS after adjusting for known prognostic factors. No interaction between race and treatment was observed.

Conclusions and Relevance:

In this secondary analysis of a randomized clinical trial studying androgen deprivation therapy with first- or second-generation androgen receptor pathway inhibitors, both Black and White patients demonstrated similar OS and PFS. Equitable access to care may reduce historical differences in outcomes between Black and White patients with advanced prostate cancer.

Trial Registration:

ClinicalTrials.gov Identifier: NCT01809691.

1

News (Medical) associated with Orteronel

04 Aug 2023

·www.drugs.com

FRIDAY, Aug. 4, 2023 -- For metastatic castration-sensitive prostate cancer (mCSPC), overall survival and progression-free survival are similar for Black and White patients receiving first- or second-generation androgen receptor pathway inhibitors within a clinical trial, according to a study published online Aug. 1 in JAMA Network Open . Nicolas Sayegh, M.D., from the University of Utah in Salt Lake City, and colleagues conducted a secondary analysis of patient-level data of a prospective phase 3 randomized clinical trial including patients with newly diagnosed mCSPC to compare survival outcomes by race. Patients receiving androgen deprivation therapy were randomly assigned to receive orteronel 300 mg orally twice daily (experimental group) or bicalutamide 50 mg orally daily (control group). Data were included for 1,313 participants: 10 and 82 percent identified as Black and White, respectively, with an equal racial distribution between the treatment groups. The researchers found that Black and White patients had similar median progression-free survival (2.3 years versus 2.9 years) and overall survival (5.5 years versus 6.3 years) at a median follow-up of 4.9 years. After adjustment for known prognostic factors, the multivariable analysis confirmed similar progression-free and overall survival. There was no interaction observed between race and treatment. "These results support the hypothesis that equitable access to care as available in a clinical trial setting negates disparities in outcomes previously associated with Black patient populations," the authors write. Several authors disclosed ties to the biopharmaceutical industry. Abstract/Full Text Posted August 2023

Phase 3Clinical Result

100 Deals associated with Orteronel

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External Link

KEGG	Wiki	ATC	Drug Bank
D10146	Orteronel	-	DB12066

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Castration-sensitive prostate cancer	Phase 3	US	Millennium Pharmaceuticals, Inc.	08 Mar 2013
Prostatic cancer metastatic	Phase 3	US	Millennium Pharmaceuticals, Inc.	08 Mar 2013
Prostatic Cancer	Phase 3	US	Radiation Therapy Oncology Group	01 May 2012
Prostatic Cancer	Phase 3	US	National Cancer Institute	01 May 2012
Prostatic Cancer	Phase 3	CA	National Cancer Institute	01 May 2012
Prostatic Cancer	Phase 3	CA	Radiation Therapy Oncology Group	01 May 2012
Metastatic castration-resistant prostate cancer	Phase 3	US	Excel Pharma Studies, Inc.	15 Nov 2010
Metastatic castration-resistant prostate cancer	Phase 3	US	Takeda Pharmaceutical Co., Ltd.	15 Nov 2010
Metastatic castration-resistant prostate cancer	Phase 3	JP	Takeda Pharmaceutical Co., Ltd.	15 Nov 2010
Metastatic castration-resistant prostate cancer	Phase 3	JP	Excel Pharma Studies, Inc.	15 Nov 2010

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


SWOG-1216 (ASCO2023) Manual	Phase 3	Prostatic Cancer	1,279	ADT±orteronel (Black patients)	svvljsfila(qssetalxbi) = PSA responses (≤ 0.2 ng/mL) at month 7 were similar in both groups. juvfilwnsr (pilitfvwhn ) View more	Positive	31 May 2023
				ADT±orteronel (White patients)
NCT01809691 (S1216 \| SWOG S1216, ASCO2023)	Phase 3	Metastatic castration-resistant prostate cancer	1,279	ADT + Orteronel	tvbsxvsslb(bqrwukipyj) = yhbfqbmqlx orstceabke (qpthdkmuuz ) View more	-	31 May 2023
				ADT + Bicalutamide	tvbsxvsslb(bqrwukipyj) = lgmkislfyw orstceabke (qpthdkmuuz ) View more
NCT01809691 (S1216 \| SWOG S1216, ASCO2023)	Phase 3	Castration-Resistant Prostatic Cancer	1,313	Androgen deprivation + Orteronel	xuavbtokqd(ffwwpshdeq): HR = 1.58 (95% CI, 1.09 - 2.29) View more	-	31 May 2023
				Androgen deprivation
NCT01546987 (CTgov)	Phase 3	Prostatic Cancer	239	Radiation therapy (ADT + RT)	geiunrpzol(kinopklihp) = wbpqjfnpzr omwjijyoyh (emcbijdflx, fskoifdjha - jlyuooevxz) View more	-	18 Apr 2023
				Radiation therapy+TAK-700 (TAK-700 + ADT + RT)	geiunrpzol(kinopklihp) = gtzpzkdxes omwjijyoyh (emcbijdflx, oxdpqmpnea - clzhsiqksy) View more
NCT01809691 (S1216, CTgov)	Phase 3	Castration-sensitive prostate cancer \| Prostatic cancer metastatic	1,313	TAK-700 LHRH agonist+TAK-700+Leuprolide (LHRHa + TAK-700)	amlgraxrou(ymfswzjkvz) = ztxcjzswlp aetjhbdsxk (bzgcbvhsgx, obxnppukaf - mwjkbhfmuj) View more	-	08 Sep 2022
				Bicalutamide (LHRHa + Bicalutamide)	amlgraxrou(ymfswzjkvz) = blbmyxywec aetjhbdsxk (bzgcbvhsgx, hkasjteyrw - xsmaafivyr) View more
NCT01809691 (S1216 \| SWOG 1216, Pubmed \| J Urol)	Phase 3	Prostatic Cancer	1,313	Orteronel + ADT	eujyjdjxhv(xkoivllibt) = hayepciyem gqnnpmdzbx (yguakurvac ) View more	Negative	21 Apr 2022
				Bicalutamide + ADT	eujyjdjxhv(xkoivllibt) = eqwaqgtozt gqnnpmdzbx (yguakurvac ) View more
NCT01084655 (CTgov)	Phase 1/2	Metastatic castration-resistant prostate cancer	38	TAK-700+Prednisone+Docetaxel (Phase 1: Orteronel 200 mg BID + Docetaxel + Prednisone)	dbmdosgqok(kgacajsfcr) = aqtqnqvbrb ngruqfxfqz (exsgjmkndj, litypoyvzs - pnafpnvity) View more	-	30 Jul 2019
				TAK-700+Prednisone+Docetaxel (Phase 1: Orteronel 400 mg BID + Docetaxel + Prednisone)	dbmdosgqok(kgacajsfcr) = rpvfwsiglr ngruqfxfqz (exsgjmkndj, rhpnnkrvla - vnurcckjcu) View more
NCT01193257 (ELM-PC 5, CTgov)	Phase 3	Metastatic castration-resistant prostate cancer	1,099	Orteronel Placebo+Prednisone (Placebo + Prednisone)	yqslbtoqzy(oucqtdmtsl) = ckbyaeqfle youiazgdfm (jdcuzueobs, bsaorxrpvc - fxpolgsobq) View more	-	19 Dec 2018
				Orteronel+Prednisone (Orteronel + Prednisone)	yqslbtoqzy(oucqtdmtsl) = jcpwkjdoye youiazgdfm (jdcuzueobs, zsnohshcdi - grxtcurten) View more
NCT01809691 (S1216 \| SWOG S1216, ESMO2018)	Phase 3	Castration-Resistant Prostatic Cancer	1,313	ADT + Orteronel	nrznvwwgmj(jrqvfyxuxn) = wifoadxpzx ncmfmsuspf (cidnitxuhp ) View more	-	22 Oct 2018
NCT01666314 (CTgov)	Phase 1/2	Prostatic Cancer \| Castration-Resistant Prostatic Cancer	137	Orteronel+prednisone (Orteronel 300 mg (Japan))	mhfrovamfc(hfhhdwakyy) = nkiprtdcso yyqnzqnola (kyoscfaidb, wrlsfrhqct - jmukxwqamb) View more	-	20 Mar 2018
				Orteronel+prednisone (Orteronel 400 mg (Ex-Japan))	brawfhvtlb(vswkixnjjn) = qydgbbxzqg laqlueysmh (uwfajsqqzp, fuqsxhqjgj - dimgftlwln) View more