This is a phase I, prospective, open-label, single center, dose finding study with Atu027 (an siRNA formulation) given as single treatment followed by repeated treatment (repeated treatment phase: 8 treatments within 4 weeks) as therapy in subjects with advanced solid cancer.

Start Date01 Jun 2009

Sponsor / Collaborator

Silence Therapeutics GmbH

100 Clinical Results associated with Atu-027

100 Translational Medicine associated with Atu-027

100 Patents (Medical) associated with Atu-027

Literatures (Medical) associated with Atu-027

01 Mar 2018·Pharmaceutical Research

Correction to: The Race of 10 Synthetic RNAi-Based Drugs to the Pharmaceutical Market

Author: Titze-de-Almeida, Ricardo ; David, Catherine ; Titze-de-Almeida, Simoneide Souza

The published article contains an error in Figure 5. The term "Atu027" should be substituted by "Patisiran" in figure and legend.

01 Jul 2017·Pharmaceutical ResearchQ3 · MEDICINE

The Race of 10 Synthetic RNAi-Based Drugs to the Pharmaceutical Market

Q3 · MEDICINE

Review

Author: Titze-de-Almeida, Ricardo ; David, Catherine ; Titze-de-Almeida, Simoneide Souza

Ten years after Fire and Melo's Nobel Prize for discovery of gene silencing by double-stranded RNA, a remarkable progress was achieved in RNA interference (RNAi). Changes in the chemical structure of synthetic oligonucleotides make them more stable and specific, and new delivery strategies became progressively available. The attention of pharmaceutical industry rapidly turned to RNAi, as an opportunity to explore new drug targets. This review addresses nine small-interfering RNAs (siRNAs) and one unique microRNA (miRNA) inhibitor, which entered the phase 2-3 clinical trials. The siRNAs in focus are PF-04523655, TKM-080301, Atu027, SYL040012, SYL1001, siG12D-LODER (phase 2), QPI-1002, QPI-1007, and patisiran (phase 3). Regarding miRNAs, their content can be down- or up-regulated, by using miRNA inhibitors (AntimiRs) or miRNA mimics. Miravirsen is an AntimiR-122 for hepatitis C virus infection. The flexibility of RNAi technology is easily understood taking into account: (i) the different drug targets (i.e. p53, caspase 2, PKN3, β2-adrenergic receptor, mutated KRAS, microRNAs); (ii) therapeutic conditions, including ophthalmic diseases, kidney injury, amyloidosis, pancreatic cancer, viral hepatitis; and (iii) routes of administration (ocular, intravenous, subcutaneous, intratumoral). Although some issues are still matters of concern (delivery, toxicity, cost, and biological barriers), RNAi definitively opens a wide avenue for drug development.

20 Dec 2014·Journal of Clinical OncologyQ1 · MEDICINE

First-in-Human Phase I Study of the Liposomal RNA Interference Therapeutic Atu027 in Patients With Advanced Solid Tumors

Q1 · MEDICINE

Article

Author: Lange, Christian ; Giese, Klaus ; Drevs, Joachim ; Strumberg, Dirk ; Gebhardt, Frank ; Vank, Christiane ; Khan, Michael ; Schultheis, Beate ; Kaufmann, Jörg ; Santel, Ansgar ; Keil, Oliver

Purpose Atu027 is a novel liposomal RNA interference therapeutic that includes a short-interfering RNA (siRNA), which silences expression of protein kinase N3 in the vascular endothelium. Atu027 has previously been shown to inhibit local tumor invasion as well as lymph node and pulmonary metastasis in mouse cancer models. This first-in-human study aimed to assess the safety, tolerability, and pharmacokinetics of Atu027 while evaluating therapeutic effects on both primary tumors and metastatic lesions. Patients and Methods Thirty-four patients with advanced solid tumors received 10 escalating doses of Atu027 without premedication, as one single followed by eight intravenous infusions twice per week during a 28-day cycle. Response was monitored by computed tomography/magnetic resonance imaging at baseline, at the end of treatment (EoT), and at final follow-up (EoS), and was assessed according to RECIST. Results Atu027 was well tolerated up to dose levels of 0.336 mg/kg; most adverse events (AEs) were low-grade toxicities (grade 1 or 2). No maximum tolerated dose was reached. Plasma levels of siRNA strands and lipids were dose proportional, peaking during 4-hour infusion. Disease stabilization was achieved in 41% of patients at EoT (n = 14 of 34 treated patients); eight patients had stable disease at EoS, and some experienced complete or partial regression of metastases. sFLT1 (soluble variant of vascular endothelial growth factor receptor-1) decreased from pretreatment levels in most patients after dose levels 04 to 10. Conclusion Atu027 was safe in patients with advanced solid tumors, with 41% of patients having stable disease for at least 8 weeks. In view of these results, further clinical trials have been initiated, and sFLT1 will be investigated as a potential biomarker.

100 Deals associated with Atu-027

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R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Pancreatic Cancer	Phase 2	DE	Silence Therapeutics Plc	17 Dec 2013
Pancreatic Ductal Carcinoma	Phase 2	DE	Silence Therapeutics GmbH	01 Mar 2013
Advanced Malignant Solid Neoplasm	Phase 2	DE	Silence Therapeutics GmbH	01 Jun 2009
Head and Neck Neoplasms	Phase 2	GB	Silence Therapeutics Plc	-
Pancreatic adenocarcinoma metastatic	Discovery	DE	Silence Therapeutics GmbH	01 Mar 2013

Clinical Result

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00938574 (Pubmed \| J Clin Oncol)	Phase 1	Solid tumor sFLT1	34	Atu027	udlulfqyvc(chriqcvqvg) = edktnvhqnq aivlhmhmjt (cvhljuchpx )	-	20 Dec 2014
NCT00938574 (ASCO2013)	Phase 1	Advanced cancer	34	Atu027	prkupmaldd(jivswukfdg) = mrwaljocvn dyujivmyxr (cqcmvlirlg )	Positive	20 May 2013
ASCO2012	Phase 1	HR-positive/HER2-low Solid Tumors	33	Atu027	(qgulqthvev) = qmhaewwbyu cgyqxormbc (vtstvknyea ) View more	-	20 May 2012
ASCO2011	Phase 1	HR-positive/HER2-low Solid Tumors	21	Atu027	(cgdjulkcms) = jhjtwacykz oljxyhulms (kdfazhjbzc ) View more	-	20 May 2011

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