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 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, which is not an opioid, is a synthetic version of a conopeptide used by a species of marine snail, Conus magus, 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 of the center for pain and palliative medicine at the University of California, San Diego.
The synthetic version 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.
The three trials that led to approval included patients with “really refractory” pain due to causes such as 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 three pivotal trials used the Visual Analog Scale of Pain Intensity (VASPI), as the primary end point.
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 the treated with placebo or ziconotide. At 3 weeks, VASPI scores had improved by a mean of 12% from baseline vs. a 5% mean improvement for patients on placebo, 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.
Dr. Wallace said ziconotide is not associated with addiction, withdrawal, or tolerance, and it is not a controlled substance. The most common side effects are neurologic, including neurocognitive impairment and dizziness.
The drug comes with a black box warning about possible severe psychiatric symptoms and neurologic impairment during treatment, and it is contraindicated in people with a history of psychosis.