FDA's Anesthesia and Life Support Drugs Advisory Committee will evaluate Schering-Plough's Bridion (sugammadex) for the novel indication of immediate reversal of sedation March 11.

Schering is seeking approval of the selective relaxant binding agent for immediate reversal of rocuronium-induced neuromuscular blockade at three minutes after administration of rocuronium. The sponsor is positioning Bridion as an efficacious and safe alternative for Cannot Intibate, Cannot Ventilate situations, in which an immediate reversal is required. Current methods, the sponsor maintains, produce significant side effects, including cardiovascular complications.

FDA asked the committee to consider - at its first new product review since 1999 - whether the single pivotal trial supporting the indication was conducted with a clinically relevant primary endpoint and whether there is sufficient information to assess Bridion in the unique CV/CI setting (¹ Also see "Schering-Plough’s Bridion Goes Before Anesthesia Advisory Committee" - Pink Sheet, 24 January, 2008.).

In the clinical trial, an intubating dose of rocuronium was followed in three minutes by a 16 mg/kg dose of Bridion, four times the dose proposed for reversal of a "profound" blockade. According to Schering, Bridion resulted in a statistically significant (p<0.0001) and="" clinically="" relevant="" reduction="" (2.7="" minutes="" faster)="" in="" mean="" time="" to="" recovery="" of="" t1="" to="" 10="" percent,="" compared="" to="" spontaneous="" recovery="" after="" dosing="" with="" the="" relaxant="">

Schering is also seeking approval of sugammadex for routine reversal of shallow and profound rocuronium- or vecuronium-induced neuromuscular blockade. If approved, Bridion would compete with edrophonium and pyridostigmine (Valeant's Mestinon and generics), approved routine reversal agents, and with neostigmine, which is not approved for neuromuscular blockade reversal.

The committee is to evaluate whether data support use of Bridion in shallow and profound reversal. The agency appears comfortable with the proposed indications, noting that three pivotal trials showed statistically significant and clinically relevant reductions in the mean times to recovery compared to neostigmine.

However, FDA asked the panel to address safety concerns arising from preclinical data, including whether the risk for children and adult patients with fractures or surgical injury to bone has been adequately characterized based on the nonclinical data.

Bridion, which is under priority review, has a second quarter predicted user fee date and would be the first in a new class of drugs known as selective relaxant binding agents that encapsulate the muscle relaxant molecule and render it inactive.

Schering came by Bridion through its acquisition of Organon BioSciences last year (² Also see "Schering-Plough Makes Its Move, Snapping Up Organon For $14.4 Billion" - Pink Sheet, 12 March, 2007.). The firm also markets rocuronium, also inherited from Organon, under the trade name Zemuron .

-Lauren Smith (lauren.smith@elsevier.com)

Anesthesia Advisory Committee To Review Schering-Plough’s Bridion For Novel Indication

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