Delving into the Latest Updates on Volenrelaxin with Synapse

Overview

Basic Info

Drug Type

Fusion protein

Synonyms

Target

RXFP1 x albumin

Mechanism

RXFP1 agonists(Relaxin receptor 1 agonists), albumin antagonists(Serum albumin antagonists), Relaxin replacements

Therapeutic Areas

Cardiovascular DiseasesUrogenital Diseases

Active Indication

Chronic Kidney DiseasesHeart failure with normal ejection fractionChronic heart failure

Inactive Indication-

Originator Organization

Eli Lilly & Co.

Active Organization

Eli Lilly & Co.

Inactive Organization-

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

Login to view timeline

Structure/Sequence

Sequence Code 682562275H

Source: *****

The main purpose of this study is to evaluate the safety and tolerability of the study drug known as LY3540378 in healthy participants following single and multiple doses (Parts A and B) and multiple doses in Japanese (Part C) and Chinese (Part D) healthy participants. Blood tests will be performed to check how much LY3540378 gets into the bloodstream and how long it takes the body to eliminate it. This is a 4-part study and may last up to 70, 113, 113 and 113 days for each participant in Parts A, B, C, and D respectively.

Start Date17 Mar 2021

Sponsor / Collaborator

Eli Lilly & Co.

100 Clinical Results associated with Volenrelaxin

Login to view more data

100 Translational Medicine associated with Volenrelaxin

Login to view more data

100 Patents (Medical) associated with Volenrelaxin

Login to view more data

2

Literatures (Medical) associated with Volenrelaxin

20 Dec 2024·Nephrology Dialysis Transplantation

Volenrelaxin (LY3540378) increases renal plasma flow: a randomized Phase 1 trial

Article

Author: Tham, Lai San ; Verdino, Petra ; Goldsmith, Paul ; Heerspink, Hiddo J L ; Wang, Zhenzhong ; Benson, Eric A ; Wang, Xiaojun ; Saifan, Chadi G ; Testani, Jeffrey M ; Haupt, Axel ; Cherney, David Z I ; Sam, Flora

ABSTRACTBackgroundVolenrelaxin is a half-life-extended recombinant human relaxin protein developed for improving kidney perfusion and cardiorenal function. This study assessed the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of volenrelaxin following single- and multiple-ascending doses (SAD and MAD) administration.MethodsIn this Phase 1, four-part, randomized, double-blinded, placebo-controlled SAD and MAD study in healthy participants, SAD participants (n = 56) received an intravenous or subcutaneous dose of volenrelaxin or placebo in a dose-ascending manner. MAD participants (n = 77) received volenrelaxin or placebo subcutaneously once weekly for 5 weeks. Effective renal plasma flow (ERPF) and measured glomerular filtration rate (mGFR) were determined by para-aminohippurate and iohexol clearance, respectively.ResultsVolenrelaxin demonstrated an extended half-life and increased acute and chronic placebo-adjusted ERPF change from baseline by 50% and 44%, respectively (P < .0001). mGFR was unchanged, while filtration fraction and afferent/efferent renal arteriolar resistances were reduced. Systolic and diastolic blood pressures decreased, and pulse rate increased with increasing volenrelaxin exposures, demonstrating maximal model-derived placebo-adjusted changes (90% confidence interval) of –6.16 (–8.04, –4.28) mmHg, –6.10 (–7.61, –4.58) mmHg and +4.39 (+3.38, +5.39) bpm, respectively. Adverse events were mild, with no difference in orthostatic hypotension between volenrelaxin and placebo.ConclusionVolenrelaxin was well-tolerated, safe and suitable for weekly subcutaneous dosing. Volenrelaxin showed a sustained improvement in kidney perfusion upon repeated dosing, supporting further clinical development in chronic kidney disease and chronic heart failure.Clinical trial registrationNCT04768855.

01 Aug 2023·British Journal of Pharmacology

Development of a long‐acting relaxin analogue, LY3540378, for treatment of chronic heart failure

Article

Author: Paavola, Chad D. ; Bivi, Nicoletta ; Cottle, Steven R. ; Wang, Xiaojun ; Porter, Gina ; Lin, Joanne ; Beebe, Emily C. ; Nwosu, Sylvia O. ; Malherbe, Laurent ; Copeland, Victoria ; Schroeder, Richard L. ; Ferrante, Andrea ; Lee, Stacey L. ; Meyer, Catalina M. ; Coskun, Tamer ; Matkovich, Scot J. ; Heuer, Josef G. ; Zhang, Hong Y. ; Thompson, Tyran D. ; Verdino, Petra ; Abernathy, Matthew M. ; Grealish, Patrick F. ; Hansen, Ryan J. ; Hu, Charlie C. ; Siegel, Robert ; Porras, Leah L. ; Cooper, Fariba N. ; Carr, Molly C. ; Dey, Asim ; Balciunas, Aldona M.

AbstractBackground and PurposeChronic heart failure, a progressive disease with limited treatment options currently available, especially in heart failure with preserved ejection fraction (HFpEF), represents an unmet medical need as well as an economic burden. The development of a novel therapeutic to slow or reverse disease progression would be highly impactful to patients and society. Relaxin‐2 (relaxin) is a human hormone regulating cardiovascular, renal, and pulmonary adaptations during pregnancy. A short‐acting recombinant relaxin, Serelaxin, demonstrated short‐term heart failure symptom relief and biomarker improvement in acute heart failure trials. Here, we present the development of a long‐acting relaxin analogue to be tested in the treatment of chronic heart failure.Experimental ApproachLY3540378 is a long‐acting protein therapeutic composed of a human relaxin analogue and a serum albumin‐binding VHH domain.Key ResultsLY3540378 is a potent agonist of the relaxin family peptide receptor 1 (RXFP1) and maintains selectivity against RXFP2/3/4 comparable to native relaxin. The half‐life of LY3540378 in preclinical species is extended through high affinity binding of the albumin‐binding VHH domain to serum albumin. When tested in a single dose administration, LY3540378 elicited relaxin‐mediated pharmacodynamic responses, such as reduced serum osmolality and increased renal blood flow in rats. In an isoproterenol‐induced cardiac hypertrophy mouse model, treatment with LY3540378 significantly reduced cardiac hypertrophy and improved isovolumetric relaxation time. In a monkey cardiovascular safety study, there were no adverse observations from administration of LY3540378.Conclusion and ImplicationsLY3540378 demonstrated to be a suitable clinical development candidate, and is progressing in clinical trials.

100 Deals associated with Volenrelaxin

Login to view more data

R&D Status

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Heart failure with normal ejection fraction	Phase 2	PL	Eli Lilly & Co.	03 Feb 2023
Heart failure with normal ejection fraction	Phase 2	ES	Eli Lilly & Co.	03 Feb 2023
Heart failure with normal ejection fraction	Phase 2	CZ	Eli Lilly & Co.	03 Feb 2023
Heart failure with normal ejection fraction	Phase 2	US	Eli Lilly & Co.	03 Feb 2023
Heart failure with normal ejection fraction	Phase 2	HU	Eli Lilly & Co.	03 Feb 2023
Heart failure with normal ejection fraction	Phase 2	AR	Eli Lilly & Co.	03 Feb 2023
Heart failure with normal ejection fraction	Phase 2	TR	Eli Lilly & Co.	03 Feb 2023
Heart failure with normal ejection fraction	Phase 2	JP	Eli Lilly & Co.	03 Feb 2023
Heart failure with normal ejection fraction	Phase 2	BR	Eli Lilly & Co.	03 Feb 2023
Chronic heart failure	Phase 2	US	Eli Lilly & Co.	-

Login to view more data

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04768855 (Pubmed \| Nephrol Dial Transplant)	Phase 1	-	-	Volenrelaxin	rcmlmwhspz(ngubrcieqf) = Adverse events were mild, with no difference in orthostatic hypotension between volenrelaxin and placebo cfgqycixfy (vtxwezuygs )	Positive	20 Dec 2024