Pain Therapeutics' Window of Opportunity

Pain Therapeutics Inc., which started up in 1998 and went public just two years later in a hot market, thinks it can turn Purdue Pharma's patent problems to its own advantage-and go it one better. Long before the OxyContin patents were deemed invalid, Purdue was struggling with the fact that its extended-release painkiller had become a drug of abuse. People looking for a quick high found they could get one by crushing "Oxies" or dissolving them in alcohol--thus circumventing the innovation in formulation that made OxyContin so effective at treating pain. Pain Therapeutics believes it has a way around the abuse problem.

Big-selling pharmaceuticals with aging or vulnerable patent protection always attract the attention of would-be generic competitors—and increasingly, of start-up companies hoping they can improve on an established drug and ride their predecessors' coattails to profit.

So it's hardly surprising that a number of firms are angling for a piece of the $2 billion market for oxycodone (OxyContin), the potent painkiller developed by Purdue Pharma LP . Patents protecting OxyContin were declared invalid at the start of this year in district court in New York, but generic competitors are waiting and hoping for the decision to be affirmed by the Federal Circuit Court before launching their own versions of oxycodone—lest they be found liable for damages if the lower court's decision is overturned. (See "Purdue Battles Generics, Early," IN VIVO, February 2004 (Also see "Purdue Battles Generics, Early" - In Vivo, 1 Feb, 2004.).)

Pain Therapeutics Inc. , which started up in 1998 and went public just two years later in a hot market, thinks it can turn Purdue's problems to its own advantage—and go it one better. Long before the OxyContin patents were deemed invalid, Purdue was struggling with the fact that its extended-release painkiller had become a drug of abuse. People looking for a quick high found they could get one by crushing "Oxies" or dissolving them in alcohol--thus circumventing the innovation in formulation that made OxyContin so effective at treating pain.

Pain Therapeutics believes it has a way around the abuse problem. In late June, the firm reported Phase II trial results for its own version of oxycodone (Remoxy) that showed, compared to OxyContin, less of the active ingredient was released in the minutes and hours after consumption—thwarting attempts to catch a high. Though the trial involved just ten patients, Pain Therapeutics' president and CEO Remi Barbier says the data is sufficient to show that Remoxy is "abuse-resistant."

Doctors and patients concerned about the stigma now surrounding OxyContin might possibly feel more comfortable with a product that is not so amenable to abuse—but how much of a premium, if any, that attribute might command in the market is not clear.

Pain Therapeutics may have a better shot at success with another opioid painkiller it calls PT-801 (Oxytrex)—that is, if it can prove and also communicate why the compound is superior. Barbier claims that Oxytrex is the first opiate drug to have a new mechanism of action since morphine was discovered 100 years ago. He explains that opioids typically act through an inhibitory pathway to block pain signals, but that over time, the drugs cause excitatory effects that are implicated in both tolerance and addiction. He says Oxytrex selectively inhibits this excitatory effect, "sort of like Cox-2 inhibitors: blocking one pathway and leaving the other alone."

The mechanism behind this drug's candidate is "a big deal," Barbier asserts, "because it solves the number one problem with opioids [which is] a narrow therapeutic window—the difference between a therapeutic and a toxic dose." The ability to expand the therapeutic window is valuable, he says, because it will allow patients to take less drug, or take an equivalent dose and get more pain relief—without increasing potentially dangerous side effects. A Phase II trial of Oxytrex vs. oxycodone showed that patients got on average 40% more pain relief from the same dosage strength, Barbier says, adding, "It's a breakthrough—but the general public and Wall Street do not understand this crucial difference between potency and therapeutic window. Everyone keeps saying, ‘Just take more drug,' but you have to keep your eye on two separate gauges.

"We're a confusing story because we have to speak in words. But if you're in pain and relieved, that's all you need to know," Barbier declares. "The way we see it is, Oxytrex is to opioids what Cox-2 inhibitors are to NSAIDs. Nobody really believed until the very end that you could make a better aspirin, but ultimately celecoxib (Celebrex) did distinguish itself by having a better therapeutic window—by being better than drugs whose side effects become intolerable when you take just a little more."

But Celebrex and its close competitor, rofecoxib (Vioxx), both were launched by huge marketing powerhouses. As yet, Pain Therapeutics has no marketing partner—and it won't for a while. Until the data is in and the products are approved, Oxytrex and Remoxy are "not on the table," Barbier declares. "The Who's Who of CNS companies have conducted due diligence and are interested," he says, "but we're too close to an answer to give away the upside."

An initial Phase III trial of Oxytrex begun in June 2003 tests the compound against placebo and oxycodone in patients with severe chronic lower back pain. A second Phase III trial begun this March tests the drug in severe chronic osteoarthritic pain. Purdue's OxyContin is now widely prescribed for these conditions, but it was initially approved for cancer pain—a focused market that mid-sized Purdue could detail by itself. Oxytrex, on the other hand, seems to have been deliberately groomed to go to larger markets.

Barbier acknowledges that a small company selling a chronic-care drug on its own "can never do as well as a Pfizer," but that realization isn't forcing him into the arms of a big partner. He says, "So maybe we won't do as good a job marketing in the first few years, compared to what a Big Pharma company could do…but we could have 100% of, say, a $100 million or $200 million pie, versus 25% of a much bigger pie." Taking the time to mull the best course of action "isn't a delay strategy," Barbier insists: "If Oxytrex works, it's worth billions. We're maintaining our flexibility."