Delving into the Latest Updates on AC-480 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

+ [1]

Target

EGFR x HER2

Mechanism

EGFR antagonists(Epidermal growth factor receptor erbB1 antagonists), HER2 antagonists(Receptor protein-tyrosine kinase erbB-2 antagonists)

Therapeutic Areas

NeoplasmsNervous System Diseases

Active Indication-

Inactive Indication

Advanced Malignant Solid NeoplasmHER2-Expressing CancersMalignant glioma of brain+ [3]

Originator Organization

Bristol Myers Squibb Co.

Active Organization-

Inactive Organization

Ambit Biosciences Corp.

Bristol Myers Squibb Co.

Drug Highest PhasePendingPhase 1

First Approval Date-

Regulation-

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Structure

Molecular FormulaC27H28ClFN8O3

InChIKeyCOUSSRGSHIJMMN-FTBISJDPSA-N

CAS Registry873837-23-1

View All Structures (2)

AC480IV will be administered as a monotherapy and then in combination with docetaxel in patients with locally advanced or metastatic solid tumors for whom there are no standard or curative therapies available. It is designed to evaluate the safety and pharmacokinetic parameters of AC480IV as monotherapy and also in combination with docetaxel under the conditions of the study.

Start Date01 Nov 2010

Sponsor / Collaborator

Daiichi Sankyo, Inc.

NCT00979173 / CompletedPhase 1IIT

A Pharmacokinetic Study of AC480 Administered Twice Daily in Surgically Resectable Malignant Glioma Patients Not on Enzyme-Inducing Anticonvulsants

The primary objective is to evaluate the intratumoral and plasma pharmacokinetics of AC480 among patients who are candidates for a resection with a recurrent malignant glioma who are not on CYP-3A enzyme inducing anti-epileptic drugs (EIAEDS). Secondary objectives include the following: to evaluate the antiproliferative effect of AC480 by FDG-PET Scan; to evaluate the safety and tolerability of AC480; and, to describe 6-month progression-free survival (PFS) and radiographic response.
This is a single institution, open label, pharmacokinetic study of AC480 in patients with recurrent malignant glioma. The study will enroll 5 patients who are not on enzyme inducing anti-epileptic drugs (EIAEDs) and are scheduled to undergo salvage surgical resection for preoperative treatment with AC480 at 300 mg orally twice daily (BID) for 14 (plus or minus 2) days before surgery (Part I- Induction Therapy). After surgery (Part II- Maintenance Therapy), patients will continue to be dosed with AC480 until disease progression or intolerance, and will be evaluated after every other cycle (1 cycle is 28 days).

Start Date01 Nov 2009

Sponsor / Collaborator

Duke University

[+1]

NCT00207012 / CompletedPhase 1

Continuous Dosing Phase I Study of BMS-599626 in Patients With HER2-Expressing Advanced Solid Malignancies

This is a continuous dosing Phase I Study of BMS-599626 in patients with HER2-expressing advanced solid malignancies.

Start Date01 May 2004

Sponsor / Collaborator

Bristol Myers Squibb Co.

100 Clinical Results associated with AC-480

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100 Translational Medicine associated with AC-480

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100 Patents (Medical) associated with AC-480

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150

Literatures (Medical) associated with AC-480

24 Nov 2023·Circulation Journal

Relationship Between Direct Oral Anticoagulant Doses and Clinical Outcomes in Elderly Patients With Non-Valvular Atrial Fibrillation　― ANAFIE Registry Sub-Analysis ―

Article

Author: Okumura, Ken ; Tsutsui, Hiroyuki ; Ikeda, Takanori ; Takita, Atsushi ; Yamashita, Takeshi ; Hirayama, Atsushi ; Toyoda, Kazunori ; Yasaka, Masahiro ; Atarashi, Hirotsugu ; Morishima, Yoshiyuki ; Kimura, Tetsuya ; Yamaguchi, Takenori ; Koretsune, Yukihiro ; Suzuki, Shinya ; Teramukai, Satoshi ; Shimizu, Wataru ; Inoue, Hiroshi ; Akao, Masaharu

BACKGROUNDThis sub-analysis of the ANAFIE Registry, a prospective, observational study of >30,000 Japanese non-valvular atrial fibrillation (NVAF) patients aged ≥75 years, assessed the prevalence of direct oral anticoagulant (DOAC) under-dose prevalence, identified the factors of under-dose prescriptions, and examined the relationship between DOAC dose and clinical outcomes.Methods and Results: Patients, divided into 5 groups by DOAC dose (standard, over-, reduced, under-, and off-label), were analyzed for background factors, cumulative incidences, and clinical outcome risk. Endpoints were stroke/systemic embolic events (SEE), major bleeding, and all-cause death during the 2-year follow-up. Of 18,497 patients taking DOACs, 20.7%, 3.8%, 51.6%, 19.6%, and 4.3%, were prescribed standard, over-, reduced, under-, and off-label doses. Factors associated with under-dose use were female sex, age ≥85 years, reduced creatinine clearance, history of major bleeding, polypharmacy, antiplatelet agents, heart failure, dementia, and no history of catheter ablation or cerebrovascular disease. After confounder adjustment, under-dose vs. standard dose was not associated with the incidence of stroke/SEE or major bleeding but was associated with a higher mortality rate. Patients receiving an off-label dose showed similar tendencies to those receiving an under-dose; that is, they showed the highest mortality rates for stroke/SEE, major bleeding, and all-cause death.CONCLUSIONSInappropriate low DOAC doses (under- or off-label dose) were not associated with stroke/SEE or major bleeding but were associated with all-cause death.

01 Oct 2023·Advances in therapy

Unintended Consequences of Increased Out-of-Pocket Costs During Medicare Coverage Gap on Anticoagulant Discontinuation and Stroke.

Article

Author: Kharat, Akshay ; Greatsinger, Alexandra ; Laliberté, François ; Lefebvre, Patrick ; Jian-Yu, E ; Desai, Urvi ; Zacharia, Nina ; Bookhart, Brahim ; Salam, Tabassum

INTRODUCTIONThis study aims to assess the risk of direct oral anticoagulant (DOAC) discontinuation among Medicare beneficiaries with non-valvular atrial fibrillation (NVAF) who reach the Medicare coverage gap stratified by low-income subsidy (LIS) status and the impact of DOAC discontinuation on rates of stroke and systemic embolism (SE) among beneficiaries with increased out-of-pocket (OOP) costs due to not receiving LIS.METHODSIn this retrospective cohort study, Medicare claims data (2015-2020) were used to identify beneficiaries with NVAF who initiated rivaroxaban or apixaban and entered the coverage gap during ≥ 1 year. DOAC discontinuation rates during the coverage gap were stratified by receipt of Medicare Part D Low-Income Subsidy (LIS), a proxy for not experiencing increased OOP costs. Among non-LIS beneficiaries, incidence rates of stroke and SE during the subsequent 12 months were compared between beneficiaries who did and did not discontinue DOAC in the coverage gap.RESULTSAmong 303,695 beneficiaries, mean age was 77.3 years, and 28% received LIS. After adjusting for baseline differences, non-LIS beneficiaries (N = 218,838) had 78% higher risk of discontinuing DOAC during the coverage gap vs. LIS recipients (adjusted hazard ratio [aHR], 1.78; 95% CI [1.73, 1.82]). Among non-LIS beneficiaries, DOAC discontinuation during coverage gap (N = 91,397; 34%) was associated with 14% higher risk of experiencing stroke and SE during the subsequent 12 months (aHR, 1.14; 95% CI [1.08, 1.20]).CONCLUSIONIncreased OOP costs during Medicare coverage gap were associated with higher risk of DOAC discontinuation, which in turn was associated with higher risk of stroke and SE among beneficiaries with NVAF.

01 Sep 2023·Current Oncology Reports

Direct Oral Anticoagulants for Cancer-Associated Venous Thromboembolism

Review

Author: Porto, Italo ; Spallarossa, Paolo ; Toma, Matteo ; Masini, Marta ; Ameri, Pietro

AbstractPurpose of ReviewTo present the randomized controlled trial (RCT) evidence and highlight the areas of uncertainty regarding direct oral anticoagulants (DOAC) for cancer-associated venous thromboembolism (CAT).Recent FindingsIn the last years, four RCTs have shown that rivaroxaban, edoxaban, and apixaban are at least as effective as low-molecular-weight heparin (LMWH) for the treatment of both incidental and symptomatic CAT. On the other hand, these drugs increase the risk of major gastrointestinal bleeding in patients with cancer at this site. Another two RCTs have demonstrated that apixaban and rivaroxaban also prevent CAT in subjects at intermediate-to-high risk commencing chemotherapy, albeit at the price of higher likelihood of bleeding. By contrast, data are limited about the use DOAC in individuals with intracranial tumors or concomitant thrombocytopenia. It is also possible that some anticancer agents heighten the effects of DOAC via pharmacokinetic interactions, up to making their effectiveness-safety profile unfavorable.SummaryLeveraging the results of the aforementioned RCTS, current guidelines recommend DOAC as the anticoagulants of choice for CAT treatment and, in selected cases, prevention. However, the benefit of DOAC is less defined in specific patient subgroups, in which the choice of DOAC over LMWH should be carefully pondered.

100 Deals associated with AC-480

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB12318

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Malignant glioma of brain	Phase 1	US	Ambit Biosciences Corp.	01 Nov 2009
Recurrent Glioma	Phase 1	US	Ambit Biosciences Corp.	01 Nov 2009
HER2-Expressing Cancers	Phase 1	FR	Bristol Myers Squibb Co.	01 May 2004
HER2-Expressing Cancers	Phase 1	ES	Bristol Myers Squibb Co.	01 May 2004
Refractory Malignant Solid Neoplasm	Phase 1	FR	Bristol Myers Squibb Co.	01 May 2004
Refractory Malignant Solid Neoplasm	Phase 1	ES	Bristol Myers Squibb Co.	01 May 2004
Advanced Malignant Solid Neoplasm	Phase 1	US	Bristol Myers Squibb Co.	01 Mar 2004
Neoplasm Metastasis	Phase 1	US	Bristol Myers Squibb Co.	01 Mar 2004

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ASCO2005	Phase 1	Metastatic Solid Tumor	13	BMS-599626	xebxwdcjfl(ziiwoahklt) = cbqqnyponw piavehomru (edkokiofdg ) View more	-	01 Jun 2005
ASCO2005	Phase 1	HR-positive/HER2-low Solid Tumors	-	BMS-599626	lnpmpsqpvs(mwidickpux) = ssorahvjlg xwkzpfhuvb (lmkjnydwcs ) View more	-	01 Jun 2005