An intrathecal formulation of a synthetic version of a toxin used by a fish-eating marine snail to catch its prey has been approved as a treatment for severe, chronic pain.
The Food and Drug Administration approved the nonopiod ziconotide for intrathecal (IT) infusion for managing severe chronic pain “in patients for whom intrathecal therapy is warranted and who are intolerant of or refractory to other treatment, such as systemic analgesics, adjunctive therapies, or IT morphine.” It is being marketed under the trade name Prialt by Elan Pharmaceuticals Inc.
Ziconotide is a synthetic version of a conopeptide used by the Conus magus sea snail to sting fish. In nature the toxin “is so powerful it stops the fish dead in its track, and the snail eats it,” said Mark Wallace, M.D., director, center for pain and palliative medicine at the University of California, San Diego.
The synthetic version of this “conotoxin” is an N-type calcium channel antagonist. N-type calcium channels are located mainly in the dorsal horn cells of the spinal cord, predominantly on the superficial layers, in the area of substantia gelatinosa where pain fibers synapse, Dr. Wallace explained.
Ziconotide “blocks those calcium channels at the level where these pain fibers meet up,” essentially shutting them down, he said, noting that opioids also have the same effect.
The three trials that led to the approval included patients with “really refractory” pain due to various causes, including low back pain, cancer pain, neuropathic pain, pain from nervous system injuries, and HIV-related pain, said Dr. Wallace, an investigator in the studies and a consultant to the manufacturer.
The most recent trial was a multicenter study in 220 patients with severe chronic pain, described by most as refractory to treatments including IT morphine.
Patients were first taken off IT medications and stabilized on analgesics that included opiates and then treated with placebo or ziconotide.
At 3 weeks, pain scores had improved by a mean of 12% from baseline vs. a mean of 5% for patients given placebo therapy, which was a highly significant difference.
During treatment, the use of non-IT opioids dropped by 24% among patients on ziconotide, compared with 17% among those on placebo.