Delving into the Latest Updates on Metyrapone with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Cormeto, Metirapona, Metycor

+ [8]

Target

CYP11B1

Mechanism

CYP11B1 inhibitors(Steroid 11-beta-hydroxylase inhibitors)

Therapeutic Areas

Nervous System DiseasesEndocrinology and Metabolic DiseaseOther Diseases

Active Indication

Adrenal InsufficiencyCushing SyndromePituitary ACTH Hypersecretion

Inactive Indication

Endogenous Cushing Syndrome

Originator Organization

Novartis SA

Active Organization

HRA Pharma Development SARL

Novartis AGHRA Pharma Rare Diseases SAS

+ [2]

Inactive Organization-

Drug Highest PhaseApproved

First Approval Date

US (04 Dec 1961),

Pituitary ACTH Hypersecretion

RegulationOrphan Drug (US)

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Structure/Sequence

Molecular FormulaC14H14N2O

InChIKeyFJLBFSROUSIWMA-UHFFFAOYSA-N

CAS Registry54-36-4

The purpose of this study is to determine the importance in the acute stress response induced by psilocybin (the primary component of "magic mushrooms") in facilitating positive outcomes. Participants in this study will be given psilocybin in combination with a placebo or metyrapone, a cortisol synthesis inhibitor medication, on four different occasions.

Start Date01 Feb 2025

Sponsor / Collaborator

University of Calgary

NCT06556277

/ RecruitingNot ApplicableIIT

Acute Consequences of Glucocorticoid Secretion in Overweight and Obese Individuals During Maximum Calorie Intake: a Double-blind, Randomized, Placebo-controlled, Cross-over Study

The investigator aim to understand whether food-induced glucocorticoids influence fat mass in overweight and obese people.
In a randomized, cross-over study, 23 overweight and obese volunteers will receive a block and replace therapy that mimics physiological glucocorticoid (GC) rhythm (metyrapone plus hydrocortisone) or placebo. Participants will undergo two identical overfeeding periods with each treatment. With the block and replace therapy food-induced GC peak will be suppressed. Metabolic and immunological parameters will be compared to reveal the effects of GCs during excessive overfeeding, particularly to understand changes in body fat.

Start Date01 Sep 2024

Sponsor / Collaborator-

NCT06106295

/ RecruitingPhase 2IIT

Metyrapone Intervention in Patients With Mild Autonomous Cortisol Secretion (MACS)

The purpose of this study is to find out whether the study drug, metyrapone, is safe and effective in treating participants with Mild Autonomous Cortisol Secretion (MACS).

Start Date19 Dec 2023

Sponsor / Collaborator

Mayo Clinic

100 Clinical Results associated with Metyrapone

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100 Translational Medicine associated with Metyrapone

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100 Patents (Medical) associated with Metyrapone

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4,724

Literatures (Medical) associated with Metyrapone

01 Feb 2025·Pituitary

Medical management pathways for Cushing’s disease in pituitary tumors centers of excellence (PTCOEs)

Article

Author: Laws, E ; Nachtigall, L B ; Haberbosch, L ; Casanueva, F F ; Chanson, P ; Barkan, A ; Popovic, V ; Lely, A J van der ; Lamberts, S ; Freda, P ; Biermasz, N R ; Frara, S ; Schilbach, K ; Melmed, S ; Uygur, M M ; Kaiser, U B ; Giustina, A ; Wass, J A H ; Gadelha, M

PURPOSE:

A recent update of consensus guidelines for the management of Cushing's disease (CD) included indications for medical therapy. However, there is limited evidence regarding their implementation in clinical practice. This study aimed to evaluate current medical therapy approaches by expert pituitary centers through an audit conducted to validate the criteria of Pituitary Tumors Centers of Excellence (PTCOEs) and provide an initial standard of medical care for CD.

METHODS:

Based on the activities of nine international PTCOEs between 2018 and 2020, we evaluated patients under medical treatment and their biochemical control rates.

RESULTS:

The median number of active patients with CD per center was 117 (35-279), with a median number of 10 new patients with CD managed annually in the endocrinology units of PTCOEs (4-42). The median percentage of patients with CD receiving medical treatment was 13.3% (4.8-82.9). Ketoconazole was the most frequently used drug, with a median rate of usage of 26.5% (5-66.7) of those receiving medical therapy. The median rates of metyrapone and pasireotide use were 17.2% (0-50) and 9.3% (0-51.7), respectively. For cabergoline and osilodrostat, therapy, the median rates of use were 2.8% (0-33.3), and 1.7% (0-25), respectively. Combination therapy was reported to be utilized in 13.6% (0-45.5) of medically treated patients. Mifepristone was used in a single center, representing 1.1% of its medically treated patients. Overall, the median control rate in patients with CD receiving medical treatment was 75% (10-100).

CONCLUSION:

Adrenal steroidogenesis inhibitors were the most commonly used medications amongst the centers. Despite the use of combination therapy, up to 25% of patients did not achieve disease control even in PTCOEs, highlighting the need for either more efficient combination therapies or novel therapeutic options.

01 Feb 2025·TOXICOLOGY

An ex vivo model of systemically-mediated effects of ozone inhalation on the brain

Article

Author: Thomson, Errol M ; Rose, Mercedes

Air pollution is associated with increased risk of neurodegenerative and neuropsychiatric conditions. While animal models have increased our understanding of how air pollution contributes to brain pathologies - including through oxidative stress, inflammatory, and stress hormone pathways - investigation of underlying mechanisms remains limited due to a lack of human-relevant models that incorporate systemic processes. Our objective was to establish an ex vivo approach that enables assessment of the roles of plasma mediators in pollutant-induced effects in the brain. As a proof-of-concept for application in the human context, we assessed whether such effects reproduced in vivo responses to pollutant exposure. Primary rat hippocampal neurons and microglia were each treated with plasma collected from rats immediately or 24 h after ozone inhalation (0 or 0.8 ppm) ± pre-treatment with the glucocorticoid synthesis inhibitor metyrapone. Microglia were further challenged with lipopolysaccharide to evaluate modification of inflammatory responses. Plasma from the ozone-exposed group produced transcriptional changes (inflammatory, antioxidant, glucocorticoid-responsive) in neurons, some of which were glucocorticoid-dependent. Ex vivo and hippocampal responses were strongly correlated, establishing the in vivo relevance of the model. Plasma from the ozone-exposed group modified inflammatory responses to lipopolysaccharide challenge in microglia, demonstrating the model's utility to assess functional changes resulting from pollutant exposure. This study establishes that an ex vivo approach can reproduce ozone-induced effects in the brain. The model was sensitive to specific plasma mediators and temporal effects, and enabled assessment of functional responses. This approach may serve to investigate mechanisms underlying effects of pollutants on the human brain.

01 Feb 2025·BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

Depression decreases immunity and PD-L1 inhibitor efficacy via the hypothalamic–pituitary–adrenal (HPA) axis in triple-negative breast cancer

Article

Author: Huang, Runze ; Gan, Chen ; Cai, Yinlian ; Cheng, Ling ; Xu, Jian ; Cheng, Huaidong ; Li, Wen ; Yu, Sheng ; Yao, Senbang ; Zhang, Qianqian

BACKGROUND:

Depression weakens antitumor immunity, yet the underlying mechanisms linking depression and tumor growth remain unclear. This study examines the influence of depression on the hypothalamic-pituitary-adrenal (HPA) axis, immunological function, and effectiveness of immunotherapy in triple-negative breast cancer (TNBC) patients.

METHODS:

A mouse model of comorbid TNBC and depression was established via chronic restraint stress (CRS) and 4T1 tumor transplantation. A programmed cell death ligand 1 (PD-L1) inhibitor was used to manage mice with TNBC, and the ability of metyrapone to reverse the immune system changes induced by HPA axis activation in depression was evaluated. Mouse peripheral blood was used to measure HPA axis activity, immune cell numbers and cytokine levels.

RESULTS:

Depression activates the HPA axis, leading to increased levels of glucocorticoids. Depression led to an increase in the B-cell number and a reduction in the CD4⁺ T-cell and CD8⁺ T-cell numbers, without a statistically significant difference in the regulatory T (Treg) cell number. Furthermore, depression increased the levels of the cytokines interferon-gamma (IFN-γ), interleukin (IL)-1β, IL-4, IL-6, IL-8, and tumor necrosis factor (TNF)-α while decreasing the levels of IL-2 and IL-10. Similar results were observed in the context of PD-L1 inhibitor therapy. The depressed mice presented an increased tumor burden and a poor response to the PD-L1 inhibitor. The application of metyrapone during PD-L1 inhibitor treatment resulted in partial restoration of these depression-related alterations.

CONCLUSIONS:

Depression reduces the effectiveness of PD-L1 inhibitors by altering the number of immune cells and the levels of cytokines through activation of the HPA axis.

TRANSLATIONAL RELEVANCE:

Depression is common in breast cancer patients and is associated with reduced antitumor immunity. There is limited knowledge regarding the specific mechanisms through which depression impairs antitumor immunity. Immunotherapy, which promotes the restoration of antitumor immunity, represents a promising treatment strategy for TNBC patients. However, the efficacy of immunotherapy can be compromised by depressive symptoms and the administration of glucocorticoids during treatment. It is still uncertain whether increasing glucocorticoid levels can reduce the efficacy of immunotherapy in patients with depression. The potential benefits of combining immunotherapy with glucocorticoid inhibitors compared with immunotherapy alone need to be evaluated for TNBC patients with concurrent depressive symptoms. Therefore, further clarification of the specific mechanisms by which depression impairs antitumor immunity is needed to inform future optimization of immunotherapy strategies.

5

News (Medical) associated with Metyrapone

10 Jul 2024

·www.esteve.com

ESTEVE ACQUIRES HRA PHARMA RARE DISEASES

ESTEVE has completed the acquisition of HRA Pharma Rare Diseases, a business specialized in rare diseases, from Perrigo Company plc. With this acquisition, ESTEVE expands its portfolio in rare and severe diseases adding, to the current existing offer, three new medications to treat Cushing's syndrome and adrenocortical carcinoma: Metopirone, Lysodren, and Ketoconazole HRA. HRA Pharma Rare Diseases has been a leading company for over 15 years in rare and severe diseases, providing the best care and services to individuals living with rare diseases, and is committed to supporting healthcare professionals worldwide. "This acquisition allows us to accelerate our international expansion, strengthening our global presence and ability to better address unmet needs, thus improving the lives of more people," highlights Staffan Schüberg, Chief Executive Officer of ESTEVE. With annual net revenues in 2023 of approximately 50 million euros, HRA Pharma Rare Diseases has a presence in numerous European countries and the United States with a team of 49 individuals. This agreement represents an investment of up to 275 million euros, structured with an initial fixed contribution and future variable payments tied to revenue. Share

Acquisition

26 Apr 2024

·firstwordpharma.com

Perrigo to divest rare diseases unit to Spain's Esteve for €275 million

Perrigo is offloading its HRA Pharma Rare Diseases business to Barcelona-based pharmaceutical company Esteve Healthcare for a total of up to €275 million ($294 million) and plans to use the proceeds to help pay down its debt.The transaction, which includes €190 million in cash upfront plus up to €85 million in potential earnouts if certain sales targets are reached, is expected to close in the third quarter.The unit's three-product portfolio includes the Cushing's syndrome treatments Metopirone (metyrapone) and ketoconazole, as well as Lysodren (mitotane), which is prescribed to treat adrenal cortical carcinoma. Staffan Schüberg, chief executive at Esteve, said the deal is "another step towards the company's vision of being an international and specialist pharma company."Meanwhile, Perrigo CEO Patrick Lockwood-Taylor said the divestment "further supports our position as a leading fast-moving consumer goods company," adding that the upfront cash proceeds would allow the company "to reduce net leverage to below 4.0x by the end of 2024."

AcquisitionDrug Approval

24 Apr 2024

·www.esteve.com

ESTEVE SIGNS A BINDING OFFER TO ACQUIRE HRA PHARMA RARE DISEASES, A PERRIGO COMPANY AFFILIATE

ESTEVE has signed a binding offer with Perrigo Company plc to acquire Perrigo's HRA Pharma Rare Diseases, a business specialized in rare and ultra-rare diseases, following the information and consultation process with HRA Pharma Works Council in France and subject to the satisfaction of customary closing conditions, including receipt of regulatory approvals. ESTEVE will increase its portfolio in the rare and severe diseases therapeutic area, adding to its current portfolio three new medicines that address Cushing's syndrome and Adrenocortical Carcinoma: Metopirone, Lysodren, and Ketoconazole HRA. HRA Pharma Rare Diseases has over 15 years' experience in rare and ultra-rare diseases and is dedicated to bringing the best care and services to people living with rare diseases and committed to supporting healthcare professionals all over the world. With annual Net Revenues in 2023 around €50M, the HRA Pharma Rare Diseases business has a presence in several European countries as well as in the US. "This transaction aims to advance ESTEVE on the path of covering the unmet patients' needs, in line with ESTEVE's purpose of improving people's lives and is another step towards the company's vision of being an international specialty pharma company", concludes Staffan Schüberg, Chief Executive Officer of ESTEVE. Patrick Lockwood-Taylor, Perrigo's President and Chief Executive Officer, states: "We are pleased that ESTEVE, with its track record of growth and international footprint, will look to increase global access to these effective treatment options for all those patients in need". The binding offer is for up to €275 million, consisting of an upfront payment and potential earnout payments. The closing of the transaction should take place during the third quarter of 2024, following the required works council consultation and subject to customary regulatory approvals. Perella Weinberg Partners and Clifford Chance served as ESTEVE's lead advisors on this transaction. Morgan Stanley & Co. LLC and Wachtell, Lipton, Rosen & Katz served as Perrigo's lead advisors on this transaction.

100 Deals associated with Metyrapone

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External Link

KEGG	Wiki	ATC	Drug Bank
D00410	Metyrapone	V04CD01	DB01011

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Adrenal Insufficiency	-	Novartis AG	30 May 2014
Cushing Syndrome	AU	CHIESI Farmaceutici SpA	02 Aug 1991
Pituitary ACTH Hypersecretion	US	HRA Pharma Rare Diseases SAS	04 Dec 1961

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Endogenous Cushing Syndrome	Phase 3	BE	HRA Pharma Development SARL	01 Apr 2015
Endogenous Cushing Syndrome	Phase 3	DE	HRA Pharma Development SARL	01 Apr 2015
Endogenous Cushing Syndrome	Phase 3	HU	HRA Pharma Development SARL	01 Apr 2015
Endogenous Cushing Syndrome	Phase 3	IT	HRA Pharma Development SARL	01 Apr 2015
Endogenous Cushing Syndrome	Phase 3	PL	HRA Pharma Development SARL	01 Apr 2015
Endogenous Cushing Syndrome	Phase 3	RO	HRA Pharma Development SARL	01 Apr 2015
Endogenous Cushing Syndrome	Phase 3	ES	HRA Pharma Development SARL	01 Apr 2015
Endogenous Cushing Syndrome	Phase 3	TR	HRA Pharma Development SARL	01 Apr 2015

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT06106295 (MACS, ENDO2024)	Phase 2	cortisol \| ACTH \| DHEAS	30	Metyrapone 250 mg	akojypdfox(amcwzscuit) = iqgdquarlz rmzytxutzx (kwxkmrcyzt, 25 - 34) View more	-	01 Jun 2024
MACS (ENDO2024)	Not Applicable	-	15	Metyrapone 250mg-500mg at 6pm and 250mg at 10pm	hmdskxicge(gvxnbrbbhs) = gzpwtpouvo gvirgtqkdz (ovwlachved, 5.5) View more	Positive	01 Jun 2024
LBSAT59 (ENDO2022)	Not Applicable	ACTH \| cortisol \| DHEAS	22	Metyrapone (Patients with OIAI)	zcausjrpya(dfexjncwcw) = uerilpmcic gytwargncl (rllosvskno, 8.1 - 51) View more	-	01 Nov 2022
LBSAT59 (ENDO2022)	Not Applicable	ACTH \| cortisol \| DHEAS	22	Metyrapone (Patients without OIAI)	zcausjrpya(dfexjncwcw) = rzjwuodnyq gytwargncl (rllosvskno, 5.9 - 55) View more	-	01 Nov 2022
ENDO2021	Not Applicable	Cushing Syndrome AM serum cortisol \| PM serum cortisol \| ACTH ... View more	-	Metyrapone	vqxffaftgb(vnrhsradwu) = wqadtxksfh rautziruez (ajjrvqqcqk ) View more	Positive	03 May 2021
NCT02297945 (PROMPT, ENDO2021)	Phase 3	Endogenous Cushing Syndrome 24 hours urine free cortisol (UFC)	50	Metyrapone	jjkxozceht(ankytfxwui) = ezdwhbvcia eycqfanucg (sxugywnsqe, 291 - 8476) View more	Positive	03 May 2021
SAT-446 (ENDO2019)	Not Applicable	Prader-Willi Syndrome	45	Metyrapone (Adults with Prader-Willi Syndrome)	azpjrpvzoz(wryipbxxbq) = pupwljvjno mbcsvyosog (qzbvgbqqec )	Positive	30 Apr 2019
SUN-LB068 (ENDO2019)	Not Applicable	Neuroendocrine Tumors \| Ectopic ACTH Syndrome	-	Metyrapone	syefsvfklq(vzbpxuqcvy) = vletdxbwyz nmzxzolbfv (pocqaeuomc ) View more	Positive	30 Apr 2019
ESPE2016	Not Applicable	Cushing Syndrome	-	Metyrapone	ualpnjdyhc(mvrqaqgnhv) = tqogxbfpfn iycmhsajsn (mknyccmkpo )	-	10 Sep 2016
Pubmed \| J Clin Endocrinol Metab	Not Applicable	Cushing Syndrome	195	Metyrapone	mzekqrrgup(kyhygopxpe) = zcnwsdsael cxsxwclgbw (vaydmakzbi ) View more	Positive	01 Nov 2015
NINDS PO1 NS37520 \| NINDS R01 NS27292 (SFN2005)	Not Applicable	Ischemia	-	Metyrapone 200 mg/kg (30 min before ischemia)	cgigilbarg(fqxwqvviik) = qlefbazqdz ufrkqehqdy (mdcdaxckfv )	Positive	14 Nov 2005
NINDS PO1 NS37520 \| NINDS R01 NS27292 (SFN2005)	Not Applicable	Ischemia	-	Metyrapone 200 mg/kg (2 h after ischemia)	qkkapvqnmb(wdpktgfhvf) = tiqddphvbd uubvtkwmei (rmvczvgrce ) View more	Positive	14 Nov 2005