Delving into the Latest Updates on Orteronel with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Orteronel (JAN/USAN)

Target

CYP17A1

Action

inhibitors

Mechanism

CYP17A1 inhibitors(Steroid 17-alpha-hydroxylase inhibitors)

Therapeutic Areas

NeoplasmsUrogenital Diseases

Active Indication

Hormone-dependent prostate cancerMetastatic Prostate Carcinoma

Inactive Indication

Adenocarcinoma of prostateBone metastasesGranulosa Cell Tumor of the Ovary+ [4]

Originator Organization

Takeda Pharmaceutical Co., Ltd.

Active Organization

Millennium Pharmaceuticals, Inc.

Inactive Organization

Excel Pharma Studies, Inc.

Takeda Pharmaceutical Co., Ltd.Almac Clinical Services Ltd.

License Organization-

Drug Highest PhasePhase 3

First Approval Date-

Regulation-

Login to view timeline

Structure/Sequence

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

The Johns Hopkins University

[+1]

100 Clinical Results associated with Orteronel

Login to view more data

100 Translational Medicine associated with Orteronel

Login to view more data

100 Patents (Medical) associated with Orteronel

Login to view more data

134

Literatures (Medical) associated with Orteronel

01 Apr 2025·The Lancet Oncology

First-line talazoparib plus enzalutamide versus placebo plus enzalutamide in men with metastatic castration-resistant prostate cancer and homologous recombination repair gene alterations: patient-reported outcomes from the randomised, double-blind, placebo-controlled, phase 3 TALAPRO-2 trial

Article

Author: Carles, Joan ; Chang, Jane ; Fong, Peter C C ; Shore, Neal D ; Healy, Cynthia G ; Fizazi, Karim ; Cislo, Paul ; Fay, Andre P ; Jones, Robert J ; Joung, Jae Young ; Matsubara, Nobuaki ; Oldenburg, Jan ; Azad, Arun A ; Agarwal, Neeraj ; Niyazov, Alexander ; Saad, Fred ; Zschäbitz, Stefanie ; Dunshee, Curtis ; De Giorgi, Ugo

BACKGROUNDIn the phase 3 TALAPRO-2 trial, talazoparib plus enzalutamide significantly improved radiographic progression-free survival compared with placebo plus enzalutamide in men with metastatic castration-resistant prostate cancer harbouring alterations in genes involved in homologous recombination repair (HRR). We aimed to assess patient-reported outcomes in patients with HRR-deficient metastatic castration-resistant prostate cancer in TALAPRO-2.METHODSTALAPRO-2 is a randomised, double-blind, placebo-controlled, phase 3 trial conducted at 223 hospitals, cancer centres, and medical centres in 26 countries worldwide. Eligible participants were male patients aged 18 years or older (≥20 years in Japan) who were receiving ongoing androgen deprivation therapy, had asymptomatic or mildly symptomatic metastatic castration-resistant prostate cancer, an Eastern Cooperative Oncology Group performance status of 0 or 1, and had not received previous life-prolonging systemic therapy for castration-resistant prostate cancer or metastatic castration-resistant prostate cancer. Patients with HRR gene alterations were randomly assigned (1:1) using a centralised interactive web response system and a permuted block size of 4 to oral talazoparib 0·5 mg once daily or placebo, plus oral enzalutamide 160 mg once daily, stratified by previous second-generation androgen receptor pathway inhibitor (abiraterone or orteronel) or docetaxel (yes vs no) in the castration-sensitive setting. The sponsor, patients, and investigators were masked to allocation of talazoparib or placebo; enzalutamide was open-label. The primary endpoint was radiographic progression-free survival by blinded independent central review and has been reported previously. Patient-reported outcomes were assessed as secondary outcomes in the patient-reported outcomes population, which comprised patients from the intention-to-treat population with a baseline patient-reported outcome assessment and at least one post-baseline patient-reported outcome assessment. Patient-reported outcomes included time to definitive deterioration in global health status/quality of life (GHS/QoL) per European Organisation for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30) and prostate cancer-specific urinary symptoms per EORTC Quality of Life Questionnaire-Prostate (QLQ-PR25), and time to deterioration in pain symptoms per Brief Pain Inventory-Short Form (BPI-SF). Mean change from baseline in GHS/QoL, overall cancer and prostate cancer-specific functioning and symptoms (per EORTC QLQ-C30 and QLQ-PR25), in pain symptoms per BPI-SF, and in general health status per EQ-5D-5L were also patient-reported secondary outcomes. This study is registered with ClinicalTrials.gov, NCT03395197, and is ongoing.FINDINGSBetween Dec 18, 2018, and Jan 20, 2022, 399 patients with HRR-deficient metastatic castration-resistant prostate cancer were enrolled and randomly assigned, of whom 197 assigned to talazoparib plus enzalutamide and 197 assigned to placebo plus enzalutamide were included in the patient-reported outcome population. Median follow-up was 22·2 months (IQR 13·8-27·7) in the talazoparib plus enzalutamide group and 20·2 months (13·5-26·6) for the placebo plus enzalutamide group. Median time to definitive deterioration of GHS/QoL was longer in the talazoparib plus enzalutamide group (27·1 months [95% CI 21·2-non-estimable]) than in the placebo plus enzalutamide group (19·3 months [16·6-23·0]; hazard ratio [HR] 0·69 [95% CI 0·49-0·97]; two-sided p=0·032). Median time to definitive deterioration in urinary symptoms was also longer in the talazoparib plus enzalutamide group (non-estimable [95% CI 32·2-non-estimable]) than in the placebo plus enzalutamide group (30·2 months [24·6-non-estimable; HR 0·56 [0·34-0·93]; two-sided p=0·022). Median time to deterioration in pain symptoms was non-estimable for both treatment groups (HR 0·58 [0·33-1·01]; two-sided p=0·051). Changes from baseline in worst pain in the past 24 h (BPI-SF, question three) and in general health status (EQ-5D-5L) also favoured talazoparib plus enzalutamide versus placebo plus enzalutamide, although the differences were not clinically meaningful. Between-group differences in mean changes from baseline in GHS/QoL, functioning, and symptoms per EORTC QLQ-C30 did not reach the clinically meaningful threshold of 10 or more points, although physical, emotional, and cognitive functioning and pain favoured talazoparib plus enzalutamide. Similarly, differences in mean changes from baseline for urinary and bowel symptoms per EORTC QLQ-PR25 favoured talazoparib plus enzalutamide, but were not clinically meaningful.INTERPRETATIONThe demonstrated delays in definitive deterioration in GHS/QoL, urinary symptoms, and other functioning and symptom scales with talazoparib plus enzalutamide compared with placebo plus enzalutamide in patients with HRR-deficient metastatic castration-resistant prostate cancer provide insight that might inform clinical decisions for these patients.FUNDINGPfizer.

01 Nov 2024·European Urology Oncology

Correlation of Body Mass Index with Overall Survival Among Patients with Metastatic Hormone-sensitive Prostate Cancer: Analysis of Patient-level Data from SWOG-1216

Article

Author: Lerner, Seth P ; Agarwal, Neeraj ; Swami, Umang ; Tangen, Catherine ; Myint, Zin ; Gebrael, Georges ; Dorff, Tanya B ; Hussain, Maha H.A. ; Gupta, Shilpa ; Narang, Arshit ; Plets, Melissa ; Thompson, Ian M. ; Jo, Yeonjung ; Lerner, Seth P. ; Dorff, Tanya B. ; Hage Chehade, Chadi ; Thompson, Ian M ; Hussain, Maha H A ; Lara, Primo N. ; Lara, Primo N

Although obesity has been associated with better overall survival (OS) among patients with metastatic castration-resistant prostate cancer, its association with OS has not been extensively explored in metastatic hormone-sensitive prostate cancer (mHSPC). We conducted a post hoc exploratory analysis of patient-level data from the SWOG-1216 trial to determine whether baseline body mass index (BMI) is associated with better OS among patients with mHSPC. SWOG-1216 was an open-label, phase 3 trial that randomized patients newly diagnosed with mHSPC 1:1 to either androgen deprivation therapy (ADT) with orteronel (experimental arm) or ADT with bicalutamide (control arm). Of 1279 patients included in the analysis, 12 (0.9%) were underweight, 252 (19.7%) had normal BMI, 958 (74.9%) were overweight, and 57 (4.5%) were obese. Age, Gleason score, extent of disease burden, the incidence of visceral metastases, and treatment allocation were similar among the groups (p > 0.05), while differences in baseline prostate-specific antigen and Zubrod performance status were observed (p < 0.05). Median OS was 2.4, 5.5, 6.6, and 6.8 yr in the underweight, normal, overweight, and obese groups, respectively. After adjusting for prognostic variables, high BMI was associated with better OS (HR for each increment in BMI category: 0.829, 5% CI 0.68-0.98; p = 0.029). These findings need to be validated in other phase 3 trials. PATIENT SUMMARY: We analyzed data from a clinical trial to evaluate the association between body mass index (BMI) and overall survival among patients with metastatic hormone-sensitive prostate cancer. We found that in this group of patients, the risk of death was lower for patients with higher BMI.

14 Oct 2024·Journal of Chemical Information and Modeling

Secondary Binding Site of CYP17A1 in Enhanced Sampling Simulations

Article

Author: Bartuzi, Damian ; Kaczor, Agnieszka A. ; Wróbel, Tomasz M.

Androgens like testosterone and dihydrotestosterone play a key role in prostate cancer progression, making the enzyme CYP17A1, essential for androgen synthesis, a crucial therapeutic target. Recent studies have revealed electron density at the substrate entry channel, suggesting the presence of a secondary binding site. In this study, we calculated the binding free energy landscape of known ligands at this site using Funnel Metadynamics. Our results characterize this binding site and indicate that nonheme-interacting ligands could effectively bind to CYP17A1, providing a novel approach to the design of CYP17A1 inhibitors.

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

Login to view more data

External Link

KEGG	Wiki	ATC	Drug Bank
D10146	Orteronel	-	DB12066

R&D Status

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Metastatic castration-resistant prostate cancer	Preclinical	United States	Millennium Pharmaceuticals, Inc.	01 Oct 2010
Metastatic castration-resistant prostate cancer	Preclinical	Colombia	Millennium Pharmaceuticals, Inc.	01 Oct 2010
Metastatic castration-resistant prostate cancer	Preclinical	Taiwan Province	Millennium Pharmaceuticals, Inc.	01 Oct 2010
Metastatic castration-resistant prostate cancer	Preclinical	Russia	Millennium Pharmaceuticals, Inc.	01 Oct 2010
Metastatic castration-resistant prostate cancer	Preclinical	Czechia	Millennium Pharmaceuticals, Inc.	01 Oct 2010
Metastatic castration-resistant prostate cancer	Preclinical	Belarus	Millennium Pharmaceuticals, Inc.	01 Oct 2010
Metastatic castration-resistant prostate cancer	Preclinical	Sweden	Millennium Pharmaceuticals, Inc.	01 Oct 2010
Metastatic castration-resistant prostate cancer	Preclinical	New Zealand	Millennium Pharmaceuticals, Inc.	01 Oct 2010
Metastatic castration-resistant prostate cancer	Preclinical	Romania	Millennium Pharmaceuticals, Inc.	01 Oct 2010
Metastatic castration-resistant prostate cancer	Preclinical	Hong Kong	Millennium Pharmaceuticals, Inc.	01 Oct 2010

Login to view more data

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02101684 (GETHI2013-01 \| Greko II, Pubmed \| Clin Transl Oncol) Manual	Phase 2	Granulosa Cell Tumor of the Ovary	10	Orteronel	(umkluisipg) = uedqmnjese sfrfuuatao (tillevhcqh, 9.6 - 70.4)	Positive	30 Dec 2024
NCT01809691 (SWOG-1216, ASCO2023) Manual	Phase 3	Hormone-dependent prostate cancer	1,279	ADT±orteronel (Black patients)	(djsuvfkxzu) = PSA responses (≤ 0.2 ng/mL) at month 7 were similar in both groups. raxwuipcfl (daiwsxmvcu ) View more	Positive	31 May 2023
				ADT±orteronel (White patients)
NCT01809691 (S1216 \| SWOG S1216, ASCO2023)	Phase 3	Metastatic castration-resistant prostate cancer	1,279	Orteroneleronel	trodtuyngy(nrpajclddu) = ubndlzsqto idiiotdhza (ykwnrtoirv ) View more	-	31 May 2023
				Bicalutamidetamide	trodtuyngy(nrpajclddu) = vgrsbgwfdk idiiotdhza (ykwnrtoirv ) View more
NCT01809691 (S1216 \| SWOG S1216, ASCO2023)	Phase 3	Castration-Resistant Prostatic Cancer	1,313	Androgen deprivation + Orteronel	vmstfdcnnf(ickzyvmcpz): 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)	yteodcfoig(nmaeytoaye) = qgxenoqcor ayratykfxc (rexkppwgmd, ogefikegop - phnzffvjqr) View more	-	18 Apr 2023
				Radiation therapy+TAK-700 (TAK-700 + ADT + RT)	yteodcfoig(nmaeytoaye) = qefskgircm ayratykfxc (rexkppwgmd, hfomkijlqp - qkqlbrgbaw) View more
SWOG-1216 (Pubmed \| J Clin Oncol)	Phase 3	Hormone-dependent prostate cancer	-	Orteronel + ADT	(pwyonltbee) = tmhexfgwjm jkytrgxoxe (hisydnqhns ) View more	Negative	01 Oct 2022
				Bicalutamide + ADT	(pwyonltbee) = shebhujlbe jkytrgxoxe (hisydnqhns ) View more
NCT01809691 (S1216 \| SWOG S1216 \| SWOG-1216 \| SWOG 1216, CTgov)	Phase 3	Hormone-dependent prostate cancer \| Metastatic Prostate Carcinoma	1,313	TAK-700 LHRH agonist+TAK-700+Leuprolide (LHRHa + TAK-700)	(kjgljqmizx) = synblkdlls hbobipcqzq (fkeuwimzus, xgdclhjexp - knjjxexkse) View more	-	08 Sep 2022
				Bicalutamide (LHRHa + Bicalutamide)	(kjgljqmizx) = dujzhtmgtt hbobipcqzq (fkeuwimzus, yvlgorxmze - zsqwnlyzna) 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)	(zvdzgvypxn) = uplczmsbqo punqixmktl (xpbojpcdjl, bxierwbelv - mkckxufuhv) View more	-	30 Jul 2019
				TAK-700+Prednisone+Docetaxel (Phase 1: Orteronel 400 mg BID + Docetaxel + Prednisone)	(zvdzgvypxn) = ciizxefyvv punqixmktl (xpbojpcdjl, ofnhaqqrdb - zyxvwkbzwv) View more
NCT01193257 (ELM-PC 5, CTgov)	Phase 3	Metastatic castration-resistant prostate cancer	1,099	Orteronel Placebo+Prednisone (Placebo + Prednisone)	(ugiiozwrkc) = xxmztmmpme qcyrcmxnuo (darjivchid, jncfshypsk - kodyscaivd) View more	-	19 Dec 2018
				Orteronel+Prednisone (Orteronel + Prednisone)	(ugiiozwrkc) = utilzctqjq qcyrcmxnuo (darjivchid, cxyhsaykkq - estjwmuwco) View more
NCT01809691 (S1216 \| SWOG S1216, ESMO2018)	Phase 3	Castration-Resistant Prostatic Cancer	1,313	Orteroneleronel	hyidpdockr(qmyoxpqnjs) = agnvqcbwxu qnwmzazfym (fqretbuhfe ) View more	-	22 Oct 2018