Delving into the Latest Updates on AEG-35156 with Synapse

Overview

Basic Info

Drug Type

ASO

Synonyms

+ [3]

Target

XIAP

Mechanism

XIAP inhibitors(Inhibitor of apoptosis protein 3 inhibitors)

Therapeutic Areas

NeoplasmsImmune System DiseasesDigestive System Disorders+ [6]

Active Indication-

Inactive Indication

Acute Myeloid LeukemiaAcute Myelomonocytic LeukemiaAdvanced breast cancer+ [13]

Originator Organization

Idera Pharmaceuticals, Inc.

Active Organization-

Inactive Organization

Aegera Therapeutics, Inc.

Idera, Inc.

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Structure

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AEG35156 is a second generation antisense which targets XIAP mRNA to lower XIAP levels and the apoptotic threshold of cancer cells, enhancing their sensitivity to intrinsic death and chemotherapy. Advanced HCC is an attractive target for AEG35156 since XIAP is highly expressed in HCC and may prevent cancer cells from undergoing apoptosis. Second generation antisense molecules are known to accumulate in liver where AEG35156 may down regulate XIAP protein expression in HCC cells thus promoting their apoptotic death.

Start Date01 Mar 2009

Sponsor / Collaborator

Aegera Therapeutics, Inc.

[+1]

NCT00768339 / TerminatedPhase 1/2

AEG35156-204: A Phase 1-2, Multicenter, Open-Label Study of the X-Linked Inhibitor of Apoptosis (XIAP) Antisense AEG35156 in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia and Indolent B-Cell Lymphomas

AEG35156 has shown early evidence of activity in patients with advanced indolent B-cell lymphomas in Phase 1 trials and merits further evaluation in this disease. This trial is designed to determine the recommended dose of AEG35156 in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) and indolent B-cell lymphomas.

Start Date01 Sep 2008

Sponsor / Collaborator

Aegera Therapeutics, Inc.

[+1]

100 Clinical Results associated with AEG-35156

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100 Translational Medicine associated with AEG-35156

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100 Patents (Medical) associated with AEG-35156

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19

Literatures (Medical) associated with AEG-35156

01 Dec 2016·American Journal of Clinical Oncology

Randomized Phase II Study of the X-linked Inhibitor of Apoptosis (XIAP) Antisense AEG35156 in Combination With Sorafenib in Patients With Advanced Hepatocellular Carcinoma (HCC)

Article

Author: Jolivet, Jacques ; Lai, Maria ; Chong, Marc ; Tung, Steward ; Kwok, Chloe ; Siu, Steven W. K. ; Zee, Benny Chung-Ying ; Chiang, Chi Leung ; Lee, Francis A. S. ; Kwong, Philip ; Leung, Kwong Chuen ; Lee, Conrad ; Cheung, Foon Yiu

Objectives:This multicenter, randomized, open-label, phase II trial evaluated the efficacy and safety of AEG35156 in addition to sorafenib in patients with advanced hepatocellular carcinoma (HCC), as compared with sorafenib alone.Methods:Eligible patients were randomly assigned in a 2:1 ratio to receive AEG35156 (300 mg weekly intravenous infusion) in combination with sorafenib (400 mg twice daily orally) or sorafenib alone. The primary endpoint was progression-free survival (PFS). Other endpoints include overall survival (OS), objective response rates (ORR), and safety profile.Results:A total of 51 patients were enrolled; of them, 48 were evaluable. At a median follow-up of 16.2 months, the median PFS and OS were 4.0 months (95% CI, 1.2-4.1) and 6.5 months (95% CI, 3.9-11.5) for combination arm, and 2.6 (95% CI, 1.2-5.4) and 5.4 months (95% CI, 4.3-11.2) for sorafenib arm. Patients who had the study treatment interrupted or had dose modifications according to protocol did significantly better, in terms of PFS and OS, than those who had no dose reduction in combination arm and those in sorafenib arm. The ORR based on Choi and RECIST criteria were 16.1% and 9.7% in combination arm, respectively. The ORR was 0 in control arm. One drug-related serious adverse event of hypersensitivity occurred in the combination arm, whereas 2 gastrointestinal serious adverse events in the sorafenib arm.Conclusion:AEG35156 in combination with sorafenib showed additional activity in terms of ORR and was well tolerated. The benefit on PFS is moderate but more apparent in the dose-reduced subgroups.

01 Jun 2013·American Journal of Clinical OncologyQ4 · MEDICINE

Phase I Trial of AEG35156 an Antisense Oligonucleotide to XIAP Plus Gemcitabine in Patients With Metastatic Pancreatic Ductal Adenocarcinoma

Q4 · MEDICINE

Article

Author: Ramesh K. Ramanathan ; Diane Rensvold ; Sandy Kurtin ; Daniel D. Von Hoff ; Glen J. Weiss ; Jacques Jolivet ; Pavani Chalasani ; Chris Pretzinger ; Daruka Mahadevan

OBJECTIVESAEG35156 is an antisense oligonucleotide (ASO) that targets the X-linked inhibitor of apoptosis mRNA. Preclinical studies showed potent activity of AEG35156 in combination with gemcitabine in pancreatic ductal adenocarcinoma (PDA). A phase I study was conducted to establish the maximum-tolerated dose, safety, and antitumor activity of AEG35156 plus gemcitabine in metastatic PDA.METHODSFourteen patients with metastatic PDA were enrolled. Nine patients were treated at 350 mg IV and 5 patients at 500 mg IV of AEG35156, 3 weeks on/1 week off of a 28-day cycle. Gemcitabine was administered at 1000 mg/m(2) IV over 30 minutes immediately after AEG35156 in both groups. Because of perceived neurotoxicity dose deescalation to 350 mg was recommended.RESULTSAll 14 patients were evaluable for tolerability and toxicity. Toxicities include neutropenia (grade 3/4, 6 patients), thrombocytopenia (grade 3, 2 patients), peripheral neuropathy (grade 3, 2 patients), fatigue (grade 3, 4 patients), ascites (grade 3, 2 patients), and nausea/vomiting (grade 4, 2 patients). Five patients (45%) experienced stable disease with a median progression-free survival of 58 days (95% CI, 52-107 d).CONCLUSIONSThe maximum-tolerated dose is AEG35156 500 mg plus gemcitabine 1000 mg/m(2) given on days 1, 8, and 15 every 28 days. AEG35156 plus gemcitabine failed to show significant clinical activity in advanced PDA.

01 May 2013·Cancer LettersQ1 · MEDICINE

Pulling the plug on a cancer cell by eliminating XIAP with AEG35156

Q1 · MEDICINE

Review

Author: LaCasse, Eric C

XIAP, the X-linked inhibitor of apoptosis, is the best example of an endogenous cellular suppressor of apoptosis. XIAP is effective because it directly limits the activity of several critical death-inducing caspases, notably caspase-3, -7 and -9, either by direct enzyme inhibition or through ubiquitin-mediated proteasomal degradation. Furthermore, XIAP acts simultaneously at several nodes in the apoptotic cascade, blocking both the intrinsic and extrinsic death pathways, and thereby preventing feed-forward amplification loops that would otherwise lead to cell death. XIAP over-expression, or increased activity, is associated with cancer progression, resistance to therapy and poor prognosis. Targeting XIAP gene expression by antisense oligonucleotides, or other approaches, demonstrates anti-cancer effects with XIAP down-regulation. These early preclinical studies led to the development of a clinical candidate mixed-backbone antisense oligonucleotide, AEG35156, against XIAP for the treatment of cancer. Published clinical results for the first-in-class and first-in-human trials of AEG35156 are summarized herein, including single agent and combination chemotherapy phase-I or -II trials for solid tumors, lymphoma, and acute myeloid leukemia. These trials demonstrate the safety of AEG35156, as well as some initial promising signs of anti-cancer activity.

100 Deals associated with AEG-35156

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB06184

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Carcinoma	Phase 2	US	Aegera Therapeutics, Inc.	01 Sep 2007
Acute Myelomonocytic Leukemia	Phase 2	CA	Aegera Therapeutics, Inc.	01 Oct 2005
Acute Myelomonocytic Leukemia	Phase 2	US	Aegera Therapeutics, Inc.	01 Oct 2005
Refractory acute myeloid leukemia	Phase 2	CA	Aegera Therapeutics, Inc.	01 Oct 2005
Refractory acute myeloid leukemia	Phase 2	US	Aegera Therapeutics, Inc.	01 Oct 2005
Acute Myeloid Leukemia	Phase 2	-	Idera, Inc.	-
Hepatocellular Carcinoma	Phase 2	-	Idera, Inc.	-
Hepatocellular Carcinoma	Phase 2	-	Idera, Inc.	-
Pancreatic Cancer	Phase 2	-	Idera, Inc.	-
Pancreatic Cancer	Phase 2	-	Idera, Inc.	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00882869 (Pubmed) Manual	Phase 2	Advanced Hepatocellular Carcinoma	51	AEG35156+Sorafenib	(hufdjopfkn) = naobllrykx nuqkrrihhk (yhiahrntnl, 1.2 - 4.1) View more	Positive	01 Dec 2016
NCT00882869 (Pubmed) Manual	Phase 2	Advanced Hepatocellular Carcinoma	51	Sorafenib	(hufdjopfkn) = ujfkasutdu nuqkrrihhk (yhiahrntnl, 1.2 - 5.4) View more	Positive	01 Dec 2016
ASCO2008	Phase 1	Neoplasms	-	AEG35156	cfbzbvvkkx(rpjzwpswrb) = Three DLTs were observed at AEG35156 350mg: Grade 3 chills/lethargy (mesothelioma), grade 3 transaminitis (colon), transient grade 3 chills/tumour lysis syndrome/transaminitis (small lymphocytic lymphoma) tdrgslicnw (jeclxolwln ) View more	-	20 May 2008
ASCO2006	Phase 1	Neoplasms	16	AEG35156	(xfzibvjenf) = fbzmtjdxqn okhyrkdxrm (zakmdtdthq )	-	20 Jun 2006