A US Food and Drug Administration (FDA) panel voted unanimously to recommend sugammadex (Bridion, Merck) for reversal of moderate or deep neuromuscular blockade induced by rocuronium or vecuronium during surgery.
The Anesthetic and Analgesic Drug Products Advisory Committee also voted 13 to 1 that the company has presented sufficient information to characterize the risk for hypersensitivity/anaphylaxis and unanimously that the company has presented sufficient information to characterize the risk for cardiac dysrhythmias.
“We believe that Bridion has the potential to offer anesthesia professionals an important new option to reverse neuromuscular blockade in the surgical setting,” said David Michelson, MD, head of global clinical development for neuroscience, Merck Research Laboratories, in a company news release.
“Today’s discussion is one step in the regulatory process, and we look forward to working with the FDA as it completes the review of our New Drug Application for Bridion.”
Sugammadex binds to rocuronium and vecuronium, two neuromuscular blocking agents used to facilitate endotracheal intubation and mechanical ventilation during surgery. Sugammadex reverses the paralysis induced by the two drugs.
Overcomes Prior Regulatory Hurdles
The FDA has refused to approve the drug several times since 2007 over concerns that include adverse events such as cardiac arrhythmias, hypersensitivity reactions, and anaphylaxis. The company presented updated safety information from a pooled and integrated analysis of adverse events from phase 1 to phase 3 studies and an analysis of cases from the company’s postmarketing database at today’s meeting.
“Very rarely we have drugs that come in to anesthesia, and I presume that the same is true in other areas, that have the potential to add significantly to the armamentarium, and this is one of those drugs. That’s not to say that there aren’t concerns, that’s not to say that this drug like many drugs we use in anesthesia will have to be used carefully and thoughtfully with an eye on the potential adverse events,” said voting committee chair Randall P. Flick, MD, MPH, director, Mayo Clinic Children’s Center, Rochester, Minnesota.
The committee agreed that the drug demonstrated efficacy in clinical trials for routine reversal of neuromuscular blockade but initially expressed concern about the accuracy of claims that sugammadex caused “immediate” reversal.
“I think both the sponsor and the FDA did an excellent job in compiling a good deal of information based on past experience, and…dialogued back and forth in terms of what was needed and then what was obtained,” said temporary voting committee member Stanley J. Szefler, MD, director of the Pediatric Asthma Research Program and research medical director of the Breathing Institute at Children’s Hospital Colorado in Aurora.
In the pooled placebo-controlled phase 1 to phase 3 trials, the most frequent adverse events where the incidence was more than 2% and more than placebo, were vomiting, anesthetic complications, pain, procedural hypotension, chills, back pain, electrocardiogram QT corrected interval prolongation, and abdominal pain.
“I felt pretty comfortable with the discussion that this was a drug that was needed, that the safety profile was discussed and has opened some precautions…alerts have been put out there, and that the group who’s going to be using it could use it and feel comfortable with the management of reactions if they might occur,” Dr Szefler added.
The committee’s recommendation is not binding.