Sugammadex Study First To Show Rapid Reversal Of Profound Rocuronium-Induced Muscle Relaxation Is Possible

Schering-Plough
Corp., (NYSE: SGP) announced that a study published in the November
2008 issue of the medical journal, Anesthesiology (Vol. 109, No. 5)(1)
demonstrated that sugammadex produced a significantly more rapid recovery
from profound rocuronium-induced muscle relaxation than the conventional
reversal agent neostigmine. Importantly, this is the first comparative
study to demonstrate that rapid reversal of profound rocuronium-induced
muscle relaxation is possible. In the study, the median time to recovery
was 2.7 minutes in the sugammadex group versus 49.0 minutes in the
neostigmine group.




Sugammadex is a novel selective relaxant binding agent that works in an
entirely new and unique way to encapsulate the muscle relaxant molecule and
render it inactive. Sugammadex is approved and marketed in the European
Union as BRIDION(R).



"This study demonstrates that sugammadex is the first agent to permit
rapid reversal of a profound level of rocuronium-induced neuromuscular
blockade," said lead author R. Kevin Jones, M.D., attending
anesthesiologist, Saddleback Memorial Medical Center, Laguna Hills, Calif.
"This finding with sugammadex will likely have important clinical
implications for how muscle relaxation is managed, providing
anesthesiologists with greater control in maintaining the level of blockade
necessary during surgery, while allowing for rapid recovery once surgery is
completed."



The study, known as the Signal trial, was a Phase III, multicenter,
randomized, parallel-group, safety-assessor blinded study that compared the
efficacy and safety of sugammadex versus neostigmine/glycopyrrolate in the
reversal of profound rocuronium-induced neuromuscular blockade.
Traditionally, reversal of nondepolarizing neuromuscular blocking agents
(NMBAs) such as rocuronium or vecuronium has been achieved by using
acetylcholinesterase inhibitors, such as neostigmine. However, these older
agents cannot rapidly reverse profound neuromuscular blockade.



Neuromuscular blockade plays several critical roles in general
anesthesia. Anesthesiologists use muscle relaxation to improve surgical
conditions and to facilitate intubation and mechanical ventilation.
Reversal agents reverse the effects of muscle relaxants, enabling patients
to regain normal muscle function sooner and breathe on their own again.



Studies have shown that in clinical practice, patients are often
extubated before complete recovery has occurred, leaving the patients at
risk of associated postoperative complications such as airway obstruction
or pulmonary complications. Residual neuromuscular blockade, which is an
important cause of NMBA-associated morbidity in surgical patients, was not
reported in any patient in this study.



"These results demonstrate the efficacy of sugammadex in rapidly
reversing profound rocuronium-induced neuromuscular blockade, an option
that is not possible with conventional reversal agents," said Robert J.
Spiegel, M.D., chief medical officer and senior vice president,
Schering-Plough Research Institute. "This study shows that sugammadex
offers advantages over neostigmine and may help improve anesthesia
management in the millions of surgeries where muscle relaxation agents are
used."
















Key Findings



In the Signal study, sugammadex or neostigmine was administered at
reappearance of 1-2 post-tetanic counts (profound neuromuscular blockade).
The primary efficacy endpoint of the study was time from sugammadex or
neostigmine/glycopyrrolate administration to return of the train-of-four
(TOF) ratio to 0.9. Profound neuromuscular blockade reversal with
sugammadex 4 mg/kg was about 17 times faster than with neostigmine 70
mcg/kg (geometric mean times were 2.9 minutes versus 50.4 minutes,
respectively [P