Delving into the Latest Updates on BMS-986020 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

LPAR1

Mechanism

LPAR1 antagonists(Lysophosphatidic acid receptor Edg-2 antagonists)

Therapeutic Areas

Respiratory DiseasesSkin and Musculoskeletal DiseasesOther Diseases+ [1]

Active Indication-

Inactive Indication

Idiopathic Pulmonary FibrosisScleroderma, Diffuse

Originator Organization

Amira Pharmaceuticals, Inc.

Active Organization-

Inactive Organization

Bristol Myers Squibb Co.

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC29H26N2O5

InChIKeyGQBRZBHEPUQRPL-LJQANCHMSA-N

CAS Registry1257213-50-5

This is a two part study.
The purpose of Part A is to determine if BMS-986020 is effective in treatment of diffuse cutaneous systemic sclerosis using one dose of BMS-986020.
The purpose of Part B is to determine if BMS-986020 is effective in treatment of diffuse cutaneous systemic sclerosis using two different doses of BMS-986020.

Start Date01 Feb 2016

Sponsor / Collaborator

Bristol Myers Squibb Co.

NCT02227173 / CompletedPhase 1

Effect of BMS-986020 on the Pharmacokinetics of Montelukast, Flurbiprofen, and Digoxin as Probe Substrates for CYP2C8, CYP2C9, and P-gp

This is an open-label, single-sequence, drug-drug interaction study in healthy male and female subjects. There is no formal research hypothesis to be statistically tested. It is expected that coadministration of BMS-986020 with montelukast, flurbiprofen, and digoxin may increase the exposure of montelukast, flurbiprofen, and digoxin.

Start Date01 Sep 2014

Sponsor / Collaborator

Bristol Myers Squibb Co.

PER-025-14 / CompletedPhase 2

SAFETY AND EFFICACY OF A LYSOPHOSPHATIDIC ACID RECEPTOR ANTAGONISTIN IDIOPATHIC PULMONARY FIBROSISA MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PHASE 2 STUDY OF THE SAFETY ANDEFFICACY OF BMS-986020 IN SUBJECTS WITH IDIOPATHIC PULMONARY FIBROSIS

Start Date01 Aug 2014

Sponsor / Collaborator

Bristol-Myers Squibb Peru SA

100 Clinical Results associated with BMS-986020

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100 Translational Medicine associated with BMS-986020

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100 Patents (Medical) associated with BMS-986020

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13

Literatures (Medical) associated with BMS-986020

01 May 2024·Biomolecules & Therapeutics

Lysophosphatidic Acid Receptor 1 Plays a Pathogenic Role in Permanent Brain Ischemic Stroke by Modulating Neuroinflammatory Responses

Article

Author: Choi, Ji Woong ; Basnet, Nikita ; Tiwari, Supriya

Lysophosphatidic acid receptor 1 (LPA₁) plays a critical role in brain injury following a transient brain ischemic stroke. However, its role in permanent brain ischemic stroke remains unknown. To address this, we investigated whether LPA₁ could contribute to brain injury of mice challenged by permanent middle cerebral artery occlusion (pMCAO). A selective LPA₁ antagonist (AM152) was used as a pharmacological tool for this investigation. When AM152 was given to pMCAO-challenged mice one hour after occlusion, pMCAO-induced brain damage such as brain infarction, functional neurological deficits, apoptosis, and blood-brain barrier disruption was significantly attenuated. Histological analyses demonstrated that AM152 administration attenuated microglial activation and proliferation in injured brain after pMCAO challenge. AM152 administration also attenuated abnormal neuroinflammatory responses by decreasing expression levels of pro-inflammatory cytokines while increasing expression levels of anti-inflammatory cytokines in the injured brain. As underlying effector pathways, NF-κB, MAPKs (ERK1/2, p38, and JNKs), and PI3K/Akt were found to be involved in LPA₁-dependent pathogenesis. Collectively, these results demonstrate that LPA₁ can contribute to brain injury by permanent ischemic stroke, along with relevant pathogenic events in an injured brain.

01 Sep 2023·American Journal of Respiratory and Critical Care Medicine

External Control Arms in Idiopathic Pulmonary Fibrosis Using Clinical Trial and Real-World Data Sources

Article

Author: Long, Alexander S. ; Fischer, Aryeh ; Hong, Hwanhee ; Wruck, Lisa M. ; Burns, Leah ; Zhang, Hongtao ; Snyder, Laurie D. ; Liu, Rong ; Palmer, Scott M. ; Swaminathan, Aparna C. ; Qiu, Ying ; Yanchenko, Eric ; Stevens, Susanna R.

Rationale: Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease for which novel therapies are needed. External controls (ECs) could enhance IPF trial efficiency, but the direct comparability of ECs versus concurrent controls is unknown. Objectives: To develop IPF ECs by fit-for-purpose data standards to historical randomized clinical trial (RCT), multicenter registry (Pulmonary Fibrosis Foundation Patient Registry), and electronic health record (EHR) data and to evaluate endpoint comparability among ECs and the phase II RCT of BMS-986020. Methods: After data curation, the rate of change in FVC from baseline to 26 weeks among participants receiving BMS-986020 600 mg twice daily was compared with the BMS-placebo arm and ECs using mixed-effects models with inverse probability weights. Measurements and Main Results: At 26 weeks, the rates of change in FVC were -32.71 ml for BMS-986020 and -130.09 ml for BMS-placebo (difference, 97.4 ml; 95% confidence interval [CI], 24.6-170.2), replicating the original BMS-986020 RCT. RCT ECs showed treatment effect point estimates within the 95% CI of the original BMS-986020 RCT. Pulmonary Fibrosis Foundation Patient Registry ECs and EHR ECs experienced a slower rate of FVC decline compared with the BMS-placebo arm, resulting in treatment-effect point estimates outside of the 95% CI of the original BMS-986020 RCT. Conclusions: IPF ECs generated from historical RCT placebo arms result in comparable primary treatment effects to that of the original clinical trial, whereas ECs from real-world data sources, including registry or EHR data, do not. RCT ECs may serve as a potentially useful supplement to future IPF RCTs.

15 May 2023·Biosensors & bioelectronics

Predicting the preclinical efficacy of anti-fibrosis agents using a force-sensing fibrosis on chip system.

Article

Author: Asmani, Mohammadnabi ; Zhao, Ruogang ; Hsia, Isaac

The high attrition rate of drug candidates contributes to the long duration and high cost in modern drug development. A major barrier in drug development is the poor predicting power of the preclinical models. In the current study, a human pulmonary fibrosis on chip system was developed for the preclinical evaluation of anti-fibrosis drugs. Pulmonary fibrosis is a severe disease characterized by progressive tissue stiffening that leads to respiration failure. To recapitulate the unique biomechanical feature of the fibrotic tissues, we developed flexible micropillars that can serve as in-situ force sensors to detect the changes in the mechanical properties of engineered lung microtissues. Using this system, we modeled the fibrogenesis of the alveolar tissues including the tissue stiffening and the expression of α-smooth muscle actin (α-SMA) and pro-collagen. Two anti-fibrosis drug candidates that are currently under clinical trials (KD025 and BMS-986020) were tested for their potential anti-fibrosis efficacy and the results were compared to those of FDA-approved anti-fibrosis drugs pirfenidone and nintedanib. Both pre-approval drugs were effective in inhibiting transforming growth factor beta 1 (TGF-β1) induced increases in tissue contractile force, stiffness and expressions of fibrotic biomarkers, which are similar to the effects of FDA-approved anti-fibrosis drugs. These results demonstrated the potential utility of the force-sensing fibrosis on chip system in the pre-clinical development of anti-fibrosis drugs.

1

News (Medical) associated with BMS-986020

25 Jul 2011

·www.pharmatimes.com

Bristol-Myers Squibb to acquire Amira

Bristol-Myers Squibb has hit the acquisition trail again and is buying privately held Amira Pharmaceuticals in a deal that could be worth $475 million to the inflammatory and fibrotic diseases specialist. Under the terms of the agreement, B-MS is shelling out $325 million in an upfront fee and may make additional milestone payments totalling $150 million. Amira's lead product is AM152, an orally-available lysophosphatidic acid 1 receptor antagonist. The latter is ready to go into Phase IIa studies for the treatment of idiopathic pulmonary fibrosis and scleroderma. B-MS is also getting hold of Amira's preclinical autotaxin programme, which it believes may be useful in the treatment of neuropathic pain and cancer metastases. Elliott Sigal, head of R&D at the New York-based major, claimed that B-MS "has identified fibrotic diseases as an area of high unmet medical need that complements our research efforts in several of our therapeutic areas”. He added that the purchase of the San Diego-based firm "represents the latest example of our String of Pearls strategy, a highly targeted set of transactions designed to enrich our innovative pipeline with potential medicines to help patients in need". Amira was founded in 2005 after Merck & Co pulled its research activities in San Diego and some of the latter's scientists, including a few who helped develop the asthma blockbuster Singulair (montelukast), set up the company. It has 25 employees who will be retained in San Diego.

Acquisition

100 Deals associated with BMS-986020

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB14948

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Scleroderma, Diffuse	Phase 2	US	Bristol Myers Squibb Co.	01 Feb 2016
Scleroderma, Diffuse	Phase 2	CA	Bristol Myers Squibb Co.	01 Feb 2016
Scleroderma, Diffuse	Phase 2	GB	Bristol Myers Squibb Co.	01 Feb 2016
Scleroderma, Diffuse	Phase 2	PL	Bristol Myers Squibb Co.	01 Feb 2016
Idiopathic Pulmonary Fibrosis	Phase 2	CO	Bristol Myers Squibb Co.	31 Jan 2013
Idiopathic Pulmonary Fibrosis	Phase 2	PE	Bristol Myers Squibb Co.	31 Jan 2013
Idiopathic Pulmonary Fibrosis	Phase 2	AU	Bristol Myers Squibb Co.	31 Jan 2013
Idiopathic Pulmonary Fibrosis	Phase 2	US	Bristol Myers Squibb Co.	31 Jan 2013
Idiopathic Pulmonary Fibrosis	Phase 2	MX	Bristol Myers Squibb Co.	31 Jan 2013
Idiopathic Pulmonary Fibrosis	Phase 2	CL	Bristol Myers Squibb Co.	31 Jan 2013

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01766817 (IM136003, CTgov)	Phase 2	Idiopathic Pulmonary Fibrosis	325	BMS-986020 (BMS-986020 600 mg Once Daily)	jrcaugjawm(ebxavojneb) = xzmurpvnor xnfswbquud (zzaydpbmhh, nqablcmpnl - cfvvuyhjiq) View more	-	22 May 2019
				BMS-986020 (BMS-986020 600 mg Twice Daily)	jrcaugjawm(ebxavojneb) = kcpjtmgjlo xnfswbquud (zzaydpbmhh, sazptgaxpj - tyuybooreo) View more
NCT01766817 (IM136003, Pubmed \| Chest)	Phase 2	Idiopathic Pulmonary Fibrosis	143	BMS-986020 600 mg qd	kjkvjqpqwi(lqyuhfqhdb) = ufnfwpjlnt mvestbnjxa (fcagpjttba, -0.201 to -0.068)	Positive	01 Nov 2018
				BMS-986020 600 mg bid	kjkvjqpqwi(lqyuhfqhdb) = lzmerkprhw mvestbnjxa (fcagpjttba, -0.106 to -0.022)