two like-sized, roughly 140-patient mid-stage studies randomly assigning enrollees either doses of Z160 or a placebo over the course of six weeks. Zalicus is tracking the results by having patients report their pain level to investigators on a weekly basis. Their pain level is scored from 1 to 10 on what’s called the visual analogue scale. The goal of each trial is to bring about a meaningful reduction in that number by the end of the study.
In one study, Zalicus enrolled patients with post-herpetic neuralgia, or PHN, better known as the chronic nerve pain associated with shingles. The reason: while it’s a small patient market, Corrigan says this is the best group for assessing the effectiveness of neuropathic pain drugs, because their disorder is “most clearly, purely [caused by] neuropathic pain.” Also, the placebo response is relatively low, and accordingly, the trials aren’t huge and expensive. Plus, it’s also deemed to be the entry point to open the door to larger chronic pain conditions like diabetic peripheral neuropathy, which, in kind, require much larger trials to test. As such, it’s critical for Z160 to hit its mark in the PHN study.
In the other trial, Zalicus is testing patients with lumbosacral radiculopathy (LSR), or chronic lower back pain that comes from the compression of nerves in the base of the spine. Corrigan acknowledges this is a “shoot the moon” strategy and that it’s far less likely to work. While LSR is the largest potential market for neuropathic pain drugs, affecting about 3 to 5 percent of the population (according to Corrigan), there are no pain drugs specifically approved for the condition. Corrigan thinks this is a study design problem: many LSR studies have looked a broader population of people with lower back pain, which can be attributed to any number of factors—pyschosomatic, muscular, or otherwise—and can also just get better on its own. Zalicus has attempted to hone its patient group by giving potential enrollees neurologic exams and a straight leg raise test, but obviously those are imperfect measures. Zalicus is, at worst, hoping for a trend showing that LSR might be worth continuing to pursue.
“The strategy here is, let’s prove that it works in what everybody thinks a neuropathic pain drug should do, but at the same time let’s see if really this is a breakthrough product that can have efficacy in a condition in which it’s been hard to show,” he says.
Corrigan says that most patients with PHN come in with a score between 6 or 7, and those with LSR typically about a point lower. He says a 2-point reduction in pain is the type of result that would make Z160 competitive with Lyrica or Cymbalta.
This leaves at least three potential outcomes for Zalicus. In its ideal—albeit unlikely—world, both studies would hit, and Zalicus would try to raise cash to move the drug forward with promising data in hand. It’s more likely, however, that the results will leave the company in a gray area. If the PHN study succeeds and the back pain study flops, it would certainly temper the upside of Z160, but it could give Zalicus enough credibility to say it’s seen signs, in humans, that it might have a neuropathic pain drug. Then it could conceivably recruit partners to help test the drug in diabetic neuropathy, fibromyalgia, and other chronic pain disorders. If the back pain study succeeds and the PHN trial doesn’t, executives will be perplexed, but optimistic (“It’s still a win for us, for sure,” Corrigan says).
If both fail? That’s the doomsday scenario.
“[It] would mean we would really focus on a strategic kind of move at this point,” Corrigan says.
