OSS, The Netherlands, June 11 /PRNewswire/ -- Sugammadex - the novel selective relaxant binding agent (SRBA) being developed by Organon, the human healthcare business unit of Akzo Nobel - demonstrated in a Phase III pivotal trial a 9-12 times faster reversal of neuromuscular blockade as compared to neostigmine, without evidence of post operative residual curarization (PORC) or re-occurrence of muscle relaxation.(1),(2) The results of this pivotal Aurora trial were presented today at the 14th annual Euroanaesthesia 2007 congress in Munich, Germany.
The Aurora trial compared the efficacy of sugammadex and neostigmine for the reversal of shallow neuromuscular blockade induced by single or multiple doses of either rocuronium (Esmeron(R)/Zemuron(R)) or vecuronium (Norcuron(R)).
"Sugammadex has shown a rapid and complete reversal in this pivotal trial without evidence of PORC or re-occurrence of neuromuscular blockade. Effective reversal is critically important to ensure that patients recover quickly and completely, without the risk of breathing difficulties," commented one of the lead investigators involved in the Aurora trial, Professor M. Blobner from the Klinik für Anästhesiologie der Technischen Universität München, Germany.
Reversal agents are used during general anesthesia to reverse the effects of muscle relaxants, also called neuromuscular blocking agents (NMBAs). Reversal of neuromuscular blockade is used to reduce the risk of PORC or re-occurrence of muscle relaxation.
Phase III Trial Overview
The international, randomised, multicenter, parallel-group Aurora trial was conducted at 13 European centers and enrolled 198 patients. In the trial sugammadex was administered at reappearance of T2 and achieved significantly faster recovery of the T4/T1 ratio to 0.9 compared with neostigmine. Median time to recovery was 1.4 minutes (0.9-5.4; p<0.0001) for sugammadex versus 17.6 minutes (3.7-106.9; p<0.0001) for neostigmine following rocuronium administration; and 2.1 minutes (1.2-64.2; p<0.0001) versus 18.9 minutes (2.9-76.2); p<0.0001) respectively following vecuronium administration. There were no clinical events due to PORC or re-curarization reported for either group.(1),(2)
In total 34 patients from this trial experienced one or more adverse events (AE) that were considered at least possibly related to the study drugs: 14 in the sugammadex group and 20 in the neostigmine group. Most drug-related AEs were mild or moderate. The most commonly reported AEs (>4%) with sugammadex included dry mouth, nausea, vomiting, chills and procedural hypertension. Neostigmine was most commonly associated (>4%) with prolonged neuromuscular blockade, dry mouth, nausea, procedural complication and albumin present in urine.(1),(2)
During the congress, results from three additional Phase III trials - Libra, Spring and Crystal trials - were presented. These trials demonstrated that sugammadex was effective and well tolerated in pediatric patients, in patients with mild or moderate impaired renal function and in comparison with neostigmine-glycopyrrolate after cisatracurium. Most common AEs (>4%) considered at least possibly related to sugammadex in these studies were diarrhoea, anesthetic complication and increased D-glucosaminidase.(3),(4),(5)
In the clinical trials conducted to date, sugammadex has generally demonstrated the ability to reverse shallow and profound depths of rocuronium-induced neuromuscular blockade within 3 minutes, thereby enabling unprecedented control of the onset and offset of skeletal muscle relaxation through the use of both drugs. Sugammadex's global Phase III development program - consisting of 5 US trials and 5 European trials - completed recruitment in late 2006. The submission of the registration files for the USA, Europe and Japan are on schedule.
Notes
(1) Blobner M, Eriksson L, Scholz J, Hillebrand H, Pompei L. Sugammadex (2.0 mg/kg) significantly faster reverses shallow rocuronium-induced neuromuscular blockade compared with neostigmine (50 mcg/kg). Eur J Anaesthesiol. 2007;24(Suppl 39):125.
(2) Alvarez-Gomez JA, Wattwil M, Vanacker B, Lora-Tamayo JI, Khünl-Brady KS. Reversal of vecuronium-induced shallow neuromuscular blockade is significantly faster with sugammadex compared with neostigmine. Eur J Anaesthesiol. 2007;24(Suppl 39):124-125.
(3) Staals LM, Snoek MMJ, Flockton E, Heeringa M, Driessen JJ. The efficacy of sugammadex in subjects with impaired renal function. Eur J Anaesthesiol. 2007;24(Suppl 39):122-123.
(4) Plaud B, Meretoja O, Pohl B, Mirakhur RK, Raft J. Reversal of rocuronium-induced neuromuscular blockade with sugammadex in paediatric and adult patients. Eur J Anaesthesiol. 2007;24(Suppl 39):124.
(5) Flockton E, Scanni E, Gomar C, Shields M, Aguilera L. Sugammadex after rocuronium provides faster recovery from neuromuscular blockade than neostigmine after cisatracurium. Eur J Anaesthesiol. 2007;24(Suppl 39):123.
About Organon
Organon creates, manufactures and markets innovative prescription Medicines that improve the health and quality of human life. Through a combination of innovation and business partnerships, Organon seeks to leverage its position as a leading biopharmaceutical company in each of its core therapeutic fields: fertility, gynecology and selected areas of anesthesia. It has extensive expertise in neuroscience and a rich and focused R&D program. Research areas also include immunology and specific areas of oncology. Organon products are distributed in over 100 countries worldwide, of which more than 50 have an Organon subsidiary. Organon is the human healthcare business unit of Akzo Nobel.
Safe Harbor Statement (a)
This press release may contain statements which address such key issues as Akzo Nobel's growth strategy, future financial results, market positions, product development, pharmaceutical products in the pipeline, and product approvals. Such statements should be carefully considered, and it should be understood that many factors could cause forecasted and actual results to differ from these statements. These factors include, but are not limited to, price fluctuations, currency fluctuations, progress of drug development, clinical testing and regulatory approval, developments in raw material and personnel costs, pensions, physical and environmental risks, legal issues, and legislative, fiscal, and other regulatory measures. Stated competitive positions are based on management estimates supported by information provided by specialized external agencies. For a more comprehensive discussion of the risk factors affecting our business please see our Annual Report on Form 20-F filed with the United States Securities and Exchange Commission, a copy of which can be found on the company's corporate website www.akzonobel.com. The 2006 Annual Report on Form 20-F will be available in the second quarter of 2007.
(a) Pursuant to the U.S. Private Securities Litigation Reform Act 1995.
www.organon.com
For more information: Monique Mols, Director media relations, Tel: +31-(0)412-665440, E-mail: monique.mols@organon.com
