Remoxy is an oral, long-acting oxycodone gelatin capsule under development with Pain Therapeutics, to which we have licensed exclusive, worldwide, development and commercialization rights under a development and license agreement entered into in December 2002.
Remoxy is formulated with our ORADUR® technology which combines properties designed to resist common methods of prescription drug misuse and abuse with the convenience of twice-a-day dosing of oxycodone. Extended release oxycodone oral painkillers achieved annual sales in the U.S. of approximately $2.4 billion in 2014. We will receive payments if certain development and regulatory milestones are achieved. We also receive reimbursement for our research and development efforts on Remoxy and a manufacturing profit on our supply of key product excipients for use in Remoxy. In addition, if Remoxy is commercialized, we will receive royalties for Remoxy of between 6.0% to 11.5% of net sales depending on the sales volumes.
On June 10, 2008, a New Drug Application (NDA) for Remoxy was submitted to the U.S. Food and Drug Administration (FDA) by our licensee, Pain Therapeutics. The NDA was accepted by the FDA and granted priority review. In December 2008, Pain Therapeutics received a Complete Response Letter for the Remoxy NDA, in which the FDA determined that the NDA was not approved. According to Pain Therapeutics, the FDA indicated additional non-clinical data will be required to support the approval of Remoxy but FDA has not requested or recommended additional clinical efficacy studies prior to approval. King resubmitted the NDA in December 2010. On June 23 2011, Pfizer received a Complete Response Letter from the FDA. The issues raised in the Complete Response Letter relate primarily to manufacturing. In October 2013, Pfizer stated that, having achieved technical milestones related to manufacturing, they would continue the development program for REMOXY®. Following guidance received from the FDA earlier that year, Pfizer announced that they would proceed with the additional clinical studies and other actions required to address the Complete Response Letter received in June 2011. These new clinical studies include, in part, a pivotal bioequivalence study with the modified REMOXY formulation to bridge to the clinical data related to the original REMOXY formulation, and an abuse-potential study with the modified formulation. The additional clinical studies required to address the Complete Response Letter have been completed, although we have not seen the results. On May 11, 2015, Pain Therapeutics disclosed that it has substantially completed the transition of REMOXY from Pfizer. Pain Therapeutics also disclosed that it plans to refile the REMOXY NDA with the FDA in the first quarter of 2016, and that it believes that, if accepted, the NDA will have a six-month review cycle. Pain Therapeutics does not believe that new clinical trials are required to refile the REMOXY NDA. Pain Therapeutics also disclosed that it plans to conduct certain non-clinical activities prior to refiling the REMOXY NDA, including in vitro work that was initiated but never completed by REMOXY’s previous sponsor due to the timing of their decision to return REMOXY. Pain Therapeutics has indicated that it may take up to six months to conduct such work, depending on the workflow and availability of its consultants and vendors. Pain Therapeutics also announced that it intends to continue to retain Mallinckrodt for contract manufacturing and supply chain support for REMOXY. There can be no assurance that Pain Therapeutics will be able to resolve the concerns raised in the Complete Response Letter.
Pain Therapeutics began the first Phase III clinical trial for Remoxy in December 2004 and in September 2005 announced positive results from this trial.
In December 2007, it was announced that the pivotal Phase III trial for Remoxy had successfully met its primary endpoint (p<0.01) that was prospectively defined by the U.S. Food and Administration (FDA) during the Special Protocol Assessment process. In addition, the study achieved statistically significant results in secondary endpoints such as Quality of Analgesia (p<0.01) and Global Assessment (p<0.01).
This pivotal Phase III randomized, double-blinded, placebo-controlled, multi-center study was designed to evaluate the analgesic efficacy of twice-daily Remoxy versus placebo over a 12-week treatment period. The study randomized 412 male and female patients. All patients were diagnosed with osteoarthritis of the knee or hip, as evidenced by X-ray and clinical criteria of the American College of Rheumatology. Additionally, all patients had pain intensity scores corresponding to moderate-to-severe pain.
Following informed consent, wash-out and dose titration, patients were randomized (1:1) into a doubled-blinded treatment period (12 weeks). During treatment, patients received twice-daily Remoxy or matching placebo. The total drug dose per patient per day ranged from 10-80mg. Pain intensity scores were assessed on a Likert pain scale. Concomitant pain medications or rescue medications were not allowed at any point during the 12-week treatment period.
This Remoxy study received a Special Protocol Assessment (SPA) from the FDA. With an SPA, the study design, endpoints and statistical analyses needed to support approval were agreed upon by the FDA prior to initiating the study and are considered binding.
Pursuant to the SPA, the primary endpoint was defined as mean decrease in pain intensity scores between Remoxy and placebo during the 12-week treatment period. Top-line data indicated that the study achieved a statistically significant result in its primary endpoint (p<0.01). In addition, the study achieved statistically significant results in secondary endpoints such as Quality of Analgesia (p<0.01) and Global Assessment (p<0.01). No drug-related issues were noted in this study.