Remoxy NDA Set For Q2 Following Positive Phase III Results

Oradur technology could make the oxycodone product less susceptible to abuse and differentiate it in the market, Durect CEO Brown tells the DAILY.

Pain Therapeutics is planning a second-quarter 2008 NDA for Remoxy , a controlled-release, abuse-resistant form of oxycodone, after Phase III trial data showed significant pain control, the firm announced Dec. 6. Remoxy utilizes Durect's Oradur platform technology, which provides oxycodone in gelatin capsule form as a twice-daily dosage for pain management.

The Phase III trial was conducted under a special protocol assessment in which the drug was measured against placebo over 12 weeks in 412 osteoarthritic patients suffering moderate to severe pain.

Cupertino, Calif.-based Durect licensed Remoxy to San Mateo, Calif.-based Pain Therapeutics which in turn has sub-licensed the marketing rights to King Pharmaceuticals.

Patients received Remoxy or placebo twice daily, and no other pain therapy was permitted during the trial period. The primary endpoint was defined as decrease in pain-intensity scores.

"It was a very well conducted trial, and demonstrated statistically significant improvement in pain control," Durect CEO James Brown told "The Pink Sheet" DAILY.

Asked if an expedited review would be requested for Remoxy, Brown acknowledged that FDA usually reserves six-month reviews for life-saving drugs, but posited that this NDA could be viewed as potentially life-saving.

"Given that, what does it mean if you have a more difficult to abuse version of oxycodone for the U.S. market?" the exec said. "There are certainly people who abuse and do themselves harm and even kill themselves with these products."

"From the review standpoint, there isn't as much for the agency to look at," he added. "One might get lucky and see something before the end of [2008] -that would be pure upside."

With reported abuse of Oxycontin , Purdue Pharma's brand-name version of oxycodone, some studies show as many as two in three doctors reluctant to prescribe that drug despite its efficacy for pain relief, Brown noted. The Oradur technology, while not abuse-proof, should prove very frustrating to anyone who might seek to abuse the oxycodone in Remoxy, he said.

"If you were to crush one of our gelcaps, if you were to take a butterknife and cut it or smash it, what's inside of it looks like Vaseline almost," Brown explained "And so that's why someone can't crush it and snort it. It's very thick, viscous material."

Anyone tampering with Remoxy probably would conclude that it was not worthwhile to try to extract the active ingredient, he added. "It just would not be cost-effective," Brown told the DAILY. "It kind of takes it out of the party scene, as it were."

Asked about potential competition, Brown noted that Purdue had succeeded in getting three generic versions of Oxycontin taken off the market, with Oxycontin sales figures rebounding somewhat as a result. But Durect and its partners assert their drug will be the first abuse-resistance oxycodone formulation in the marketplace.

"We are not a generic version of Oxycontin," Brown emphasized. "We are a new NDA, this is a new formulation so it has nothing to do with Oxycontin. The only similarity is it uses oxycodone as a base agent."

In November 2005, King contracted with Pain Therapeutics and Durect, agreeing to underwrite the SPA for Remoxy after a prior 200-patient Phase III trial had shown efficacy (¹ (Also see "King Signs On To Develop Pain Therapeutics’ Abuse-Resistant Oxycodone" - Pink Sheet, 10 Nov, 2005.)). King paid $150 million upfront, with milestone payments up to $150 million, plus royalties to both Pain Therapeutics and Durect.

Durect will receive royalties starting at 6 percent of sales and increasing gradually to 11.5 percent if sales reach $1 billion, Brown told the DAILY. The company also will derive additional income from licensing excipients that make the Oradur technology work, he added.

In its deal with Pain Therapeutics, Durect licensed Oradur to be used with four specific narcotics. The three companies have agreed not to name the other three narcotics publicly. But there are compounds beyond those involved in the Pain/King deal to which Durect could apply the Oradur technology, Brown said.

"It's important also to note that we, Durect, own all these intellectual property improvements of the Oradur technology or any controlled-release technology that comes out of this alliance," he explained. "And we are free then to pursue the fifth, sixth and seventh narcotics ourselves. We do plan to have a hospital-based sales force and a surgical suite sales force for our Posidur (bupivicaine injection) product. And so it's likely that we may do one of these other narcotics, or we could do a deal with another company."

Brown hopes there are numerous other possible applications for Oradur. He predicted the technology could be applied broadly beyond pain relief drugs for anything subject to abuse or that would benefit from being in a gelcap and/or semi-liquid form. "People tend to like gelcaps - they're a bit easier to swallow," he noted.

Posidur, intended for post-operative pain, also is advancing, as Durect revealed positive Phase IIb trial results for the product in July (² (Also see "Durect Reports Positive Phase IIb Results For Posidur In Post-Op Hernia Pain" - Pink Sheet, 17 Jul, 2007.)). The drug is slated to begin Phase III soon.

-Joseph Haas ([email protected])