Safety and antihypertensive effect of switching from eplerenone to esaxerenone in hypertensive patients. - Safety and antihypertensive effect of switching from eplerenone to esaxerenone in hypertensive patients.

Start Date15 May 2024

Sponsor / Collaborator

Tokyo Women's Medical University Educational Association

JPRN-UMIN000037721 / Recruiting

Effects of adding esaxerenone to calcium channel blocker in patients with essential hypertension. - Effects of adding esaxerenone to calcium channel blocker in patients with essential hypertension.

Start Date15 May 2024

Sponsor / Collaborator

Tokyo Women's Medical University Educational Association

JPRN-jRCT1061230053 / RecruitingPhase 2

The Efficacy of Esaxerenone for Chronic Kidney Disease Patients with Uncontrolled Hypertension

Start Date28 Aug 2023

Sponsor / Collaborator-

100 Clinical Results associated with Esaxerenone

100 Translational Medicine associated with Esaxerenone

100 Patents (Medical) associated with Esaxerenone

106

Literatures (Medical) associated with Esaxerenone

01 Apr 2024·Drug metabolism and pharmacokinetics

Exposure-response analysis of the efficacy and safety of esaxerenone, a novel nonsteroidal mineralocorticoid receptor blocker, in hypertensive patients with or without diabetic kidney disease

Article

Author: Yoshihara, Kazutaka ; Wada, Russell ; Kastrissios, Helen ; Fukae, Masato ; Shimizu, Takako

BACKGROUND:

Esaxerenone is a novel non-steroidal mineralocorticoid receptor blocker. Here, we assessed efficacy and safety exposure-response relationships of esaxerenone and its covariates and thereby justified the recommended dosage regimens, focusing on the safety benefits of up-titration regimen in patients at higher risk for increased serum potassium (sK⁺).

METHODS:

The relationships between model-derived individual esaxerenone exposure and efficacy (blood pressure [BP]) and safety (increased sK⁺) were evaluated using multivariate linear regression and Cox regression analyses, respectively, using data from 1453 hypertensive patients with or without diabetic kidney disease in five clinical studies.

RESULTS:

Exposure-efficacy analyses demonstrated that higher exposure was linearly associated with greater BP reduction over the investigated dose range. Exposure-safety analyses showed that higher exposure was associated with a higher risk of increased sK⁺ under a fixed-dosing regimen; higher baseline sK⁺ and lower baseline estimated glomerular filtration rate (eGFR) were influential covariates. Model-based simulations suggested that fewer occurrences of increased sK⁺ are expected under the up-titration regimen (from 1.25 to 5 mg) relative to the fixed-dosing regimen (5 mg) in patients with different combinations of these covariates.

CONCLUSIONS:

The exposure-response analyses supported the esaxerenone recommended doses and the safety benefits of using the up-titration regimen.

01 Feb 2024·Diabetes, obesity & metabolism

Non‐steroidal mineralocorticoid receptor antagonists in patients with chronic kidney disease and type 2 diabetes

Review

Author: Solis-Herrera, Carolina ; Triplitt, Curtis

Abstract:

Chronic kidney disease (CKD) in patients with type 2 diabetes (T2D) is a major health challenge associated with a disproportionately high burden of end‐stage renal disease, cardiovascular disease and death. This review summarizes the rationale, clinical evidence and practical implementation for non‐steroidal mineralocorticoid receptor antagonists (nsMRAs), a drug class now approved and recommended for patients with T2D and CKD at risk of cardiorenal disease progression. Three nsMRAs (finerenone, esaxerenone and apararenone) have been evaluated but finerenone is currently the only approved nsMRA for this indication. Two large‐scale, placebo‐controlled, Phase 3 studies evaluated finerenone added to a maximally tolerated dose of an angiotensin‐converting enzyme inhibitor or an angiotensin II receptor blocker. Over >2 years of treatment, finerenone was associated with a significant reduction in composite endpoints of renal and cardiovascular outcomes versus placebo. Esaxerenone or apararenone have both shown significant improvements in albuminuria versus placebo. In general, nsMRAs were well tolerated. Hyperkalaemia was the most notable treatment‐related adverse event and could generally be managed through serum potassium monitoring and dose adjustments. The nsMRAs are now an important component of recommended treatment for CKD associated with T2D, providing a significant reduction in the risk of cardiorenal progression beyond what can be achieved with glucose and blood pressure control.

01 Jan 2024·Hypertension research : official journal of the Japanese Society of Hypertension

Effects of esaxerenone on blood pressure, urinary albumin excretion, serum levels of NT-proBNP, and quality of life in patients with primary aldosteronism

Article

Author: Shibata, Hirotaka ; Masaki, Takayuki ; Kinoshita, Mizuki ; Iwamoto, Miyuki ; Yoshida, Yuichi ; Noguchi, Takaaki ; Fujiwara, Mio ; Ozeki, Yoshinori ; Sada, Kentaro ; Okamoto, Mitsuhiro ; Mori, Yumi ; Gotoh, Koro ; Nagai, Satoshi ; Miyamoto, Shotaro ; Matsuda, Naoki

Primary aldosteronism (PA) is typically managed with mineralocorticoid receptor antagonists (MRAs) barring adrenalectomy. The efficacy of esaxerenone, a nonsteroidal MRA, were explored in patients with PA. Various parameters such as the urinary albumin to creatinine ratio (UACR) and serum levels of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) were evaluated in 25 PA patients before and 3 and 6 months after esaxerenone treatment. Systolic and diastolic blood pressure (BP), and the estimated glomerular filtration rate decreased after treatment, while serum levels of potassium and active renin increased. Significant reductions were observed in UACR 3 and 6 months after treatment. A significant decrease in NT-proBNP was evident at 6 months but not 3 months after treatment. Correlation analysis indicated that the reductions in BP and UACR at 3 months were independent of estimated daily salt intake. Furthermore, the effect of esaxerenone treatment on lowering UACR and NT-proBNP levels was independent of BP reduction. Responders whose systolic BP decreased 6 months after esaxerenone treatment by more than 10 mmHg compared to pretreatment had higher pretreatment NT-proBNP and similar UACR before and after treatment when compared with nonresponders. Esaxerenone improved mental, physical, and social quality of life (QOL) 6 months after treatment compared to healthy controls and increased over time. No patients discontinued treatment due to severe hyperkalemia or renal dysfunction. In conclusion, esaxerenone is a safe and effective MRA for PA treatment, offering significant benefits in terms of hypertension, albuminuria, NT-proBNP levels, and QOL improvement. Esaxerenone effectively lowers BP, UACR, and serum levels of NT-proBNP independent of dietary salt intake in mild PA patients. ARC active renin concentration, DBP diastolic blood pressure, MR mineralocorticoid receptor, MRA mineralocorticoid receptor antagonist, NT-proBNP N-terminal pro-brain natriuretic peptide, PA primary aldosteronism, QOL quality of life, SBP systolic blood pressure, SF-36 Medical Outcomes Study 36-Item Short-Form Health Survey, UACR urinary albumin to creatinine ratio.

News (Medical) associated with Esaxerenone

18 Apr 2023

·www.prnewswire.com

Ocedurenone: A Novel Therapy for Uncontrolled Hypertension in Advanced Chronic Kidney Disease

PRINCETON, N.J., April 17, 2023 /PRNewswire/ -- EMJ Nephrology interviewed two World-renowned experts in nephrology and cardiology, George Bakris and Faiez Zannad, regarding the challenges of treating uncontrolled hypertension (uHTN) in patients with advanced chronic kidney disease (CKD), a large unmet need for safe, effective therapies, and the potential of one therapy, Ocedurenone, to address this need. Original article: EMJ-8.1-2023-1.pdf (emg-health.com) Large Unmet Need Patients with advanced CKD have a high burden of disease, compounded by serious comorbidities, most commonly hypertension. Controlling hypertension is vital in these patients to reduce the associated risks of morbidity and mortality, as well as reducing cardiorenal risk, but treatment options are limited due to safety concerns with the use of existing agents. Current Options Bakris:"The PATHWAY-2 trial showed that in people with resistant hypertension without advanced CKD, spironolactone produced a greater reduction in blood pressure than a β-blocker and an α-blocker. However, it presents safety risks to patients when administered." "Then there is eplerenone, given twice a day, while safe, has a much weaker effect on blood pressure reduction than spironolactone. That's all we've got, so that's what people use." Dr Bakris also mentioned two existing nonsteroidal MRAs, esaxerenone which is "approved exclusively in Japan, for which there are no placebo-controlled comparisons", and Finerenone which "reduces blood pressure (placebo subtracted) variously from 3 mmHg (ARTS-DN, FIGARO-DKD, and FIDELIO-DKD studies) to approximately 8 mmHg (subset analysis from ARTS-DN study, eGFR of approximately 68, though office blood pressure from the same study showed around 3 mmHg reduction)". Future Option - Ocedurenone Bakris:"Now, Ocedurenone, a non-steroidal MRA, shows clear promise in patients whose standard of care includes two, three, or more drugs. Ocedurenone is the only drug that has consistently steadied resistant hypertension in people with advanced CKD." In the first dedicated study of patients with uncontrolled hypertension and advanced CKD (BLOCK-CKD), Ocedurenone demonstrated efficacy in lowering blood pressure, together with a favorable safety profile. The experts were optimistic that it could provide a much-needed treatment option for these patients, with the added potential for reduction in the risk of cardiorenal outcomes. "This study showed that Ocedurenone reduces SBP by 11 mmHg (placebo-subtracted), a reduction that could lead to potential approval. No other agent to date has steadied blood pressure as well in this group of patients. And the point is that these are the patients who need the most help." Zannad reinforced the importance of the hyperkalemia data for the clinical safety of Ocedurenone:"With Ocedurenone, we may for the first time have an MRA that is both safe and efficacious." Bakris added:"A Phase 3 study (CLARION-CKD) of Ocedurenone in a similar patient population is ongoing. I remain optimistic that the signal seen in the BLOCK-CKD study will be seen in this larger study." "I remain excited about Ocedurenone. Its tolerability and efficacy in lowering blood pressure in a very high-risk group will have a significant impact on morbidity." "Mineralocorticoid receptors are so ubiquitous which may allow for indications beyond CKD and cardiovascular conditions. This is likely just the beginning for Ocedurenone." About Ocedurenone (KBP-5074) KBP Biosciences is a global, clinical-stage biotechnology company, headquartered in Princeton, NJ, focused on discovering, developing, and commercializing innovative small-molecule therapeutics for the treatment of serious cardiorenal and infectious diseases with large unmet medical needs. Ocedurenone (KBP-5074) is a non-steroidal MRA discovered and developed by KBP Biosciences. At present, the Phase 3 clinical trial of the first indication for Ocedurenone, advanced CKD and uncontrolled hypertension, is underway. About KBP Biosciences, please visit . SOURCE KBP Biosciences

Phase 3Clinical ResultDrug Approval

10 Jan 2023

·www.biospace.com

Ajinomoto and Exelixis Enter Into a License Agreement to Discover and Develop Novel Antibody-Drug Conjugates for the Treatment of Cancer

TOKYO, Jan. 10, 2023 /PRNewswire/ -- Ajinomoto Co., Inc. ("Ajinomoto Co.") today announced a license agreement with Exelixis, Inc. ("Exelixis") to incorporate AJICAP®, Ajinomoto Co.'s proprietary site-specific bioconjugation and linker technologies, in the development of certain of Exelixis' antibody-drug conjugate (ADC) programs. Exelixis is a commercially successful, oncology-focused biotechnology company that strives to accelerate the discovery, development and commercialization of new medicines for difficult-to-treat cancers. Utilizing its network of biotherapeutics collaborations, the company is developing next generation ADCs for the treatment of various cancers. Ajinomoto Co. is a leading technology provider for biopharmaceuticals and the owner of CDMO Ajinomoto Bio-Pharma Services. AJICAP® is Ajinomoto Co.'s proprietary site-specific bioconjugation and stable linker technologies compatible with commonly used antibody isotypes. AJICAP technology includes its "off-the-shelf" feature, allowing any therapeutic antibody at any stage of development to be conjugated to drug-payloads of choice without the need for antibody engineering or cell line development, and stable/hydrophilic linkers to generate antibody-drug conjugates with an enhanced therapeutic window. As part of the license agreement, Exelixis will have the right to use the AJICAP technology to support its aim of advancing multiple ADCs with the potential for higher efficacy and lower toxicity than currently available options. Ajinomoto Co. is eligible to receive development, regulatory and commercial milestone payments as well as royalties on commercial sales. Dr. Tatsuya Okuzumi, General Manager, Business Development Group, Bio-Pharma Services Department, Ajinomoto Co., expressed: "We are very excited to support Exelixis, a leader in oncology drug discovery, development, and commercialization, in the development of novel antibody-drug conjugates. The combination of Exelixis' antibodies and payloads with Ajinomoto Co.'s AJICAP opens up a wide range of oncology applications and may be harnessed to provide a clinical benefit to patients." About Ajinomoto Co. and Ajinomoto Bio-Pharma Services Based on the corporate message "Eat Well, Live Well.", Ajinomoto Co., Inc. has been scientifically pursuing the possibilities of amino acids to aim for future growth by creating new value through sustainable and innovative solutions for communities and society. For additional information about Ajinomoto Co. (TYO: 2802), please visit . As its pharmaceutical arm, Ajinomoto Bio-Pharma Services is a fully integrated contract development and manufacturing organization (CDMO) with sites in Belgium, United States, Japan, and India, providing comprehensive development, cGMP manufacturing, and aseptic fill finish services for small and large molecule APIs and intermediates. For more information about Ajinomoto Bio-Pharma Services, please visit . In addition, Ajinomoto Co. and Ajinomoto Bio-Pharma Services offer a broad range of innovative platform technologies and capabilities for pre-clinical and pilot programs to commercial quantities, including AJIPHASE® oligonucleotide manufacturing technology, CORYNEX® and TALAMAX® protein expression systems, AJICAP® site-specific conjugation and linker technologies for ADCs, continuous flow manufacturing and more. For additional information on the platform technologies, please visit . About Exelixis, Inc. Founded in 1994, Exelixis, Inc. (Exelixis) is a commercially successful, oncology-focused biotechnology company that strives to accelerate the discovery, development and commercialization of new medicines for difficult-to-treat cancers. Following early work in model system genetics, Exelixis established a broad drug discovery and development platform that has served as the foundation for our continued efforts to bring new cancer therapies to patients in need. Exelixis' discovery efforts have resulted in four commercially available products, CABOMETYX® (cabozantinib), COMETRIQ® (cabozantinib), COTELLIC® (cobimetinib) and MINNEBRO® (esaxerenone), and Exelixis has entered into partnerships with leading pharmaceutical companies to bring these important medicines to patients worldwide. Supported by revenues from marketed products and collaborations, Exelixis is committed to prudently reinvesting in our business to maximize the potential of our pipeline. Exelixis is supplementing existing therapeutic assets with targeted business development activities and internal drug discovery — all to deliver the next generation of Exelixis medicines and help patients recover stronger and live longer. Exelixis is a member of the Standard & Poor's (S&P) MidCap 400 index, which measures the performance of profitable mid-sized companies. For more information about Exelixis, please visit , follow @ExelixisInc on Twitter or like Exelixis, Inc. on Facebook. Company Codes: Tokyo:2802, OTC-PINK:AJINY

License out/inOligonucleotide

03 Jan 2023

·www.businesswire.com

Exelixis to Present at the 41st Annual J.P. Morgan Healthcare Conference on January 9, 2023 — Presentation to be webcast on www.exelixis.com —

ALAMEDA, Calif.--( BUSINESS WIRE )--Exelixis, Inc. (Nasdaq: EXEL) today announced that Michael M. Morrissey, Ph.D., the company’s President and Chief Executive Officer, will provide a corporate overview at the 41 st Annual J.P. Morgan Healthcare Conference on Monday, January 9, 2023 at 8:15pm ET / 5:15pm PT. To access the webcast link, log onto www.exelixis.com and proceed to the News & Events / Event Calendar page under the Investors & Media heading. Please connect to the company’s website at least 15 minutes prior to the presentation to ensure adequate time for any software download that may be required to listen to the webcast. A replay will also be available at the same location for at least 30 days. About Exelixis Founded in 1994, Exelixis, Inc. (Nasdaq: EXEL) is a commercially successful, oncology-focused biotechnology company that strives to accelerate the discovery, development and commercialization of new medicines for difficult-to-treat cancers. Following early work in model system genetics, we established a broad drug discovery and development platform that has served as the foundation for our continued efforts to bring new cancer therapies to patients in need. Our discovery efforts have resulted in four commercially available products, CABOMETYX ® (cabozantinib), COMETRIQ ® (cabozantinib), COTELLIC ® (cobimetinib) and MINNEBRO ® (esaxerenone), and we have entered into partnerships with leading pharmaceutical companies to bring these important medicines to patients worldwide. Supported by revenues from our marketed products and collaborations, we are committed to prudently reinvesting in our business to maximize the potential of our pipeline. We are supplementing our existing therapeutic assets with targeted business development activities and internal drug discovery – all to deliver the next generation of Exelixis medicines and help patients recover stronger and live longer. Exelixis is a member of the Standard & Poor’s (S&P) MidCap 400 index, which measures the performance of profitable mid-sized companies. For more information about Exelixis, please visit www.exelixis.com , follow @ExelixisInc on Twitter or like Exelixis, Inc. on Facebook. Exelixis, the Exelixis logo, CABOMETYX, COMETRIQ and COTELLIC are registered U.S. trademarks. MINNEBRO is a registered Japanese trademark.

100 Deals associated with Esaxerenone

External Link

KEGG	Wiki	ATC	Drug Bank
D10892	Esaxerenone	C02	DB15207

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Hypertension	JP	Daiichi Sankyo Co., Ltd.	08 Jan 2019

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Albuminuria	Phase 3	JP	Daiichi Sankyo Co., Ltd.	01 Jun 2016
Diabetes Mellitus, Type 2	Phase 3	JP	Daiichi Sankyo Co., Ltd.	01 Jun 2016
Hypertension, Renal	Phase 3	JP	Daiichi Sankyo Co., Ltd.	01 Jun 2016
Hypertension, severe	Phase 3	JP	Daiichi Sankyo Co., Ltd.	01 Jun 2016
Essential Hypertension	Phase 3	JP	Daiichi Sankyo Co., Ltd.	01 Mar 2016
Diabetes Mellitus, Noninsulin-Dependent, 2	Phase 2	JP	Daiichi Sankyo, Inc.	01 Jan 2015
Diabetic Nephropathies	Phase 2	JP	Daiichi Sankyo, Inc.	01 Jan 2015

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02722265 (Pubmed) Manual	Phase 3	Essential Hypertension	25	esaxerenone	dtspsyidqj(tbgjekgvwn) = qoabdrkcmk vjtdlpdzdd (gnayqyuoki ) View more	Positive	17 Aug 2022
NCT02807987 (Pubmed \| Hypertens Res) Manual	Phase 3	Hypertension	91	Esaxerenone	wfnynabivs(oshtdkirmk) = owncwludoi jgmlubygzo (hfdbwmeine ) View more	Positive	01 May 2021
NCT02722265 (Pubmed \| Hypertens Res) Manual	Phase 3	Diabetes Mellitus, Type 2 \| Hypertension \| Albuminuria	51	Esaxerenone	rirvsrqejh(ikfpzpaipr) = gruqqxmwhs jkwdgkirbx (kxyfvlzywc ) View more	Positive	01 Oct 2019

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