Delving into the Latest Updates on Frovocimab with Synapse

Overview

Basic Info

Drug Type

Monoclonal antibody

Synonyms

Frovocimab (USAN)

Target

PCSK9

Mechanism

PCSK9 inhibitors(Proprotein convertase subtilisin kexin type 9 inhibitors)

Therapeutic Areas

Endocrinology and Metabolic Disease

Active Indication-

Inactive Indication

Hyper LDL cholesterolaemiaPrimary hypercholesterolemia

Originator Organization

Eli Lilly & Co.

Active Organization-

Inactive Organization

Eli Lilly & Co.

Drug Highest PhasePendingPhase 2

First Approval Date-

Regulation-

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Gene Sequence

Sequence Code 32694L

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Sequence Code 32689H

Source: *****

This study is designed to define the amount and duration of cholesterol lowering and to assess the safety and tolerability of different dose regimens of LY3015014 in participants with high cholesterol. The study will also investigate how the body processes the drug and how the drug affects the body. Participants will remain on a stable diet and will continue taking cholesterol-lowering medications (statins with or without ezetimibe). After signing the informed consent document, the participant will complete a screening/run-in period that will last at most 8 weeks. Then, the treatment period will last approximately 16 weeks. After the treatment period, the participants will complete a follow-up period lasting approximately 8 weeks for a total study duration ranging from approximately 25 to 32 weeks.

Start Date01 Jun 2013

Sponsor / Collaborator

Eli Lilly & Co.

100 Clinical Results associated with Frovocimab

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100 Translational Medicine associated with Frovocimab

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100 Patents (Medical) associated with Frovocimab

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6

Literatures (Medical) associated with Frovocimab

01 Jan 2021·BioMed Research InternationalQ3 · BIOLOGY

[Retracted] A Systematic Review and Meta‐Analysis of Therapeutic Efficacy and Safety of Alirocumab and Evolocumab on Familial Hypercholesterolemia

Q3 · BIOLOGY

ReviewOA

Author: Huang, Keke ; Yang, Huiyao ; Yu, Xin ; Zhu, Tiantian ; Xie, Shanshan ; Wan, Jinjin ; Zhang, Weifang ; Zeng, Hao ; Li, Juan ; Ge, Xiaoyue

Objectives. The aim of this study was to provide the first study to systematically analyze the efficacy and safety of PCSK9‐mAbs in the treatment of familial hypercholesterolemia (FH). Methods. A computer was used to search the electronic Cochrane Library, PubMed/MEDLINE, and Embase databases for clinical trials using the following search terms: “AMG 145”, “evolocumab”, “SAR236553/REGN727”, “alirocumab”, “RG7652”, “LY3015014”, “RN316/bococizumab”, “PCSK9”, and “familial hypercholesterolemia” up to November 2020. Study quality was assessed with the Cochrane Collaboration’s tool, and publication bias was evaluated by a contour‐enhanced funnel plot and the Harbord modification of the Egger test. After obtaining the data, a meta‐analysis was performed using R software, version 4.0.3. Results. A meta‐analysis was performed on 7 clinical trials (926 total patients). The results showed that PCSK9‐mAbs reduced the LDL‐C level by the greatest margin, WMD −49.14%, 95% CI: −55.81 to −42.47%, on FH versus control groups. PCSK9‐mAbs also significantly reduced lipoprotein (a) (Lp (a)), total cholesterol (TC), triglycerides (TG), apolipoprotein‐B (Apo‐B), and non‐high‐density lipoprotein cholesterol (non‐HDL‐C) levels and increased HDL‐C and apolipoprotein‐A1 (Apo‐A1) levels of beneficial lipoproteins. Moreover, no significant difference was found between PCSK9‐mAbs treatment and placebo in common adverse events, serious events, and laboratory adverse events. Conclusion. PCSK9‐mAbs significantly decreased LDL‐C and other lipid levels with satisfactory safety and tolerability in FH treatment.

01 Sep 2018·BMJ OpenQ4 · MEDICINE

Impact of PCSK9 monoclonal antibodies on circulating hs-CRP levels: a systematic review and meta-analysis of randomised controlled trials

Q4 · MEDICINE

ReviewOA

Author: Cao, Ye-Xuan ; Liu, Hui-Hui ; Li, Sha ; Li, Jian-Jun

ObjectiveTo evaluate the potential effects of proprotein convertase subtilisin/kexin type 9 monoclonal antibody (PCSK9-mAb) on high-sensitivity C reactive protein (hs-CRP) concentrations.DesignA systematic review and meta-analysis of randomised controlled trials.Data sourcesPubMed, MEDLINE, the Cochrane Library databases, ClinicalTrials.gov and recent conferences were searched from inception to May 2018.Eligibility criteria for selecting studiesAll randomised controlled trials that reported changes of hs-CRP were included.ResultsTen studies involving 4198 participants were identified. PCSK9-mAbs showed a slight efficacy in reducing hs-CRP (−0.04 mg/L, 95% CI: −0.17 to 0.01) which was not statistically different. The results did not altered when subgroup analyses were performed including PCSK9-mAb types (alirocumab: 0.12 mg/L, 95% CI: −0.18 to 0.43; evolocumab: 0.00 mg/L, 95% CI: −0.07 to 0.07; LY3015014: −0.48 mg/L, 95% CI: −1.28 to 0.32; RG7652: 0.35 mg/L, 95% CI: −0.26 to 0.96), treatment duration (≤12w: 0.00 mg/L, 95% CI: −0.07 to 0.07; >12w: −0.11 mg/L, 95% CI: −0.45 to −0.23), participant characteristics (familial hypercholesterolaemia: 0.00 mg/L, 95% CI: −0.07 to 0.07; non-familial hypercholesterolaemia: 0.07 mg/L, 95% CI: −0.12 to 0.26; mix: −0.48 mg/L, 95% CI: −1.28 to 0.32) and treatment methods (monotherapy: 0.00 mg/L, −0.08 to 0.07; combination therapy: −0.08 mg/L, −0.37 to 0.21). Meta-regression analyses suggested no significant linear correlation between baseline age (p=0.673), sex (p=0.645) and low-density lipoprotein cholesterol reduction (p=0.339).ConclusionsOur updated meta-analysis suggested that PCSK9-mAbs had no significant impact on circulating hs-CRP levels irrespective of PCSK9-mAb types, participant characteristics and treatment duration or methods.

17 Feb 2017·mAbsQ2 · MEDICINE

Quantitative characterization of the mechanism of action and impact of a ‘proteolysis-permitting’ anti-PCSK9 antibody

Q2 · MEDICINE

Article

Author: Berna, Michael J. ; Beyer, Thomas P. ; Sperry, Andrea E. ; Wroblewski, Victor J. ; Schroeder, Krista M. ; Eacho, Patrick I. ; Hansen, Ryan J.

A recent report described a novel mechanism of action for an anti-proprotein convertase subtilisin-kexin type 9 (PCSK9) monoclonal antibody (LY3015014, or LY), wherein the antibody has improved potency and duration of action due to the PCSK9 epitope for LY binding. Unlike other antibodies, proteolysis of PCSK9 can occur when LY is bound to PCSK9. We hypothesized that this allowance of PCSK9 cleavage potentially improves LY efficiency through two pathways, namely lack of accumulation of intact PCSK9 and reduced clearance of LY. A quantitative modeling approach is necessary to further understand this novel mechanism of action. We developed a mechanism-based model to characterize the relationship between antibody pharmacokinetics, PCSK9 and LDL cholesterol levels in animals, and used the model to better understand the underlying drivers for the improved efficiency of LY. Simulations suggested that the allowance of cleavage of PCSK9 resulting in a lack of accumulation of intact PCSK9 is the major driver of the improved potency and durability of LY. The modeling reveals that this novel 'proteolysis-permitting' mechanism of LY is a means by which an efficient antibody can be developed with a total antibody dosing rate that is lower than the target production rate. We expect this engineering approach may be applicable to other targets and that the mathematical models presented herein will be useful in evaluating similar approaches.

100 Deals associated with Frovocimab

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External Link

KEGG	Wiki	ATC	Drug Bank
D11398	-	-	DB15089

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Primary hypercholesterolemia	Phase 2	DK	Eli Lilly & Co.	01 Jun 2013
Primary hypercholesterolemia	Phase 2	PL	Eli Lilly & Co.	01 Jun 2013
Primary hypercholesterolemia	Phase 2	CZ	Eli Lilly & Co.	01 Jun 2013
Primary hypercholesterolemia	Phase 2	PR	Eli Lilly & Co.	01 Jun 2013
Primary hypercholesterolemia	Phase 2	US	Eli Lilly & Co.	01 Jun 2013
Primary hypercholesterolemia	Phase 2	CA	Eli Lilly & Co.	01 Jun 2013
Primary hypercholesterolemia	Phase 2	JP	Eli Lilly & Co.	01 Jun 2013
Primary hypercholesterolemia	Phase 2	NL	Eli Lilly & Co.	01 Jun 2013
Hyper LDL cholesterolaemia	Phase 2	US	Eli Lilly & Co.	01 Jun 2012

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01618916 (CTgov)	Phase 1	Hyper LDL cholesterolaemia	51	LY3015014 (1.0 mg/kg LY3015014 Q2W)	uawnjavceg(ykamljbjce) = oldjkxrere fvprbtwaof (gfwcfkopja, ocoanpdfuz - ngerwiubil) View more	-	25 Feb 2019
				LY3015014 (1.0 mg/kg LY3015014 Q4W)	uawnjavceg(ykamljbjce) = sugnggtfdf fvprbtwaof (gfwcfkopja, etvneyehsx - ehrctoiben) View more
NCT01671085 (CTgov)	Phase 1	Hypercholesterolemia	13	Placebo	(xjkplkzqbe) = icucafbrvr kldnpforsf (gdqtpznfkc, hftronegso - alfskchcuq) View more	-	25 Feb 2019
NCT01890967 (CTgov)	Phase 2	Primary hypercholesterolemia	527	Placebo+Ezetimibe+Statin (Placebo Q4W)	wzwdsusiss(tohiogbaoq) = eiqmnrsjsb cyhsgokmye (gciupzmgef, qhcporhfjb - hpxkkkkitk) View more	-	21 Jun 2017
				LY3015014+Ezetimibe+Statin (20 mg LY3015014 Q4W)	wzwdsusiss(tohiogbaoq) = sdmtxlaven cyhsgokmye (gciupzmgef, xfagfgcfec - larbqjzaeh) View more